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The coronavirus SARS-CoV-2 causes the severe disease COVID-19. SARS-CoV-2 infection is initiated by interaction of the viral spike protein and host receptor angiotensin-converting enzyme 2 (ACE2). We report an improved bright and reversible fluorogenic reporter, named SURF (split UnaG-based reversible and fluorogenic protein-protein interaction reporter), that we apply to monitor real-time interactions between spike and ACE2 in living cells. SURF has a large dynamic range with a dark-to-bright fluorescence signal that requires no exogenous cofactors. Utilizing this reporter, we carried out a high-throughput screening of small-molecule libraries. We identified three natural compounds that block replication of SARS-CoV-2 in both Vero cells and human primary nasal and bronchial epithelial cells. Cell biological and biochemical experiments validated all three compounds and showed that they block the early stages of viral infection. Two of the inhibitors, bruceine A and gamabufotalin, were also found to block replication of the Delta and Omicron variants of SARS-CoV-2. Both bruceine A and gamabufotalin exhibited potent antiviral activity in K18-hACE2 and wild-type C57BL6/J mice, as evidenced by reduced viral titres in the lung and brain, and protection from alveolar and peribronchial inflammation in the lung, thereby limiting disease progression. We propose that our fluorescent assay can be applied to identify antiviral compounds with potential as therapeutic treatment for COVID-19 and other respiratory diseases.

The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague–Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.

There is still a lack of consensus regarding whether suprascapular nerve decompression should be routinely performed with rotator cuff repair. Therefore, this meta-analysis aimed to evaluate whether additional suprascapular nerve release (SSNR) could improve shoulder functional outcomes and pain relief more than rotator cuff repair alone.We performed a literature review of electronic databases for noncomparative and comparative studies investigating the effect of SSNR in patients undergoing rotator cuff repair. The primary outcome was the change in shoulder function scores from the preoperative status, and the secondary outcome was the change in the visual analog scale (VAS) score of pain after surgery. A subgroup analysis was conducted based on the study design (noncomparative studies vs. comparative studies).Nine studies comprising 279 participants were included. Our analysis demonstrated that the group that underwent SSNR had a better shoulder functional score after surgery than at preoperative assessment (standardized mean difference [SMD], 1.333, 95% confidence interval [CI], 0.708-1.959). No significant differences were identified in shoulder function improvement between those with and without SSNR, with an SMD of 0.163 (95% CI, -0.091 to 0.418). Likewise, the group with SSNR showed a decreased VAS score after surgery compared to their preoperative status (SMD, 0.910; 95% CI, 0.560-1.260). However, there was no significant difference in VAS change between those with and without SSNR, with an SMD of 0.431 (95% CI, -0.095 to 0.956).The present meta-analysis revealed that SSNR might not be routinely needed in rotator cuff tendon repair as no additional benefits in functional improvement or pain relief were identified compared to rotator cuff tendon repair alone.

The purpose of this study is to compare the clinical characteristics and surgical outcomes of thoracotomy and video-assisted thoracoscopic surgery (VATS) in children with congenital lung malformations (CLMs) in a tertiary referring center and to report our modified biportal VATS setting.This is a single-center retrospective chart review study including children who underwent surgical resection for CLMs between January 2007 and December 2020. Patient characteristics and surgical outcomes were compared between open and thoracoscopy, as well as conventional VATS and biportal VATS. Biportal setting included an anterior utility wound and a camera trocar wound with one-lung ventilation.A total of 100 patients were identified. Twenty patients received thoracotomy, and 80 patients received VATS (67 conventional and 13 biportal VATS). The median age at operation was 0.4 months in the thoracotomy group and 4.7 months in the VATS group. More patients in the thoracotomy group had preoperative symptoms, comorbidities, and emergent operations. The patients who underwent thoracotomy had significantly longer postoperative ICU stays, chest tube durations, hospital stays, and more complications. The pathological analysis revealed 67 congenital pulmonary airway malformations, 27 pulmonary sequestration, 6 hybrid lesions, and one accompanying pleuropulmonary blastoma. Compared to conventional VATS, the ICU stay was shorter in the biportal VATS group, with comparable operative durations, hospital stay and complications.VATS for CLMs is associated with better postoperative recovery and fewer complications. Biportal VATS is also a safe and feasible approach.

Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies.This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM.Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used.Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included.A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently.There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay.Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.

Advanced glycation end products (AGEs) that abnormally accumulate in diabetic patients have been reported to damage bone health. We aimed to investigate the association between skin autofluorescence (SAF)-AGEThis study was nested in the prospective REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals) study and included 1214 eligible participants. SAF was used to measure skin AGEs (SAF-AGEs). Fracture events were determined by an in-person clinical follow-up. Binary logistic regression analysis, linear regression analysis, and a restricted cubic spline nested in logistic models were used to test outcomes.The overall prevalence of LBD/osteoporosis in middle-aged or elderly T2DM patients was 35.7% (n = 434), and the overall incidence of MOFs was 10.5% (n = 116). Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGEIn conclusion, SAF-AGE背景: 糖基化终末产物(AGEs)在糖尿病患者体内异常积聚，已有报道会损害骨健康。本研究旨在探讨皮肤自发荧光(SAF)-AGE

Malignant glioma, especially glioblastoma (GBM), has historically been associated with a low survival rate. The hyperactivation of STAT3 played a key role in GBM initiation and resistance to therapy; thus, there is an urgent requirement for novel STAT3 inhibitors. BP-1-102 was recently reported as a biochemical inhibitor of STAT3, but its roles and mechanism in biological behavior of glioma cells were still unclear. In this study, the effects of BP-1-102 on proliferation, apoptosis, invasion and neurosphere formation of glioma cell were investigated. Our results indicated that BP-1-102 inhibited the proliferation of U251 and A172 cells, and their IC50 values were 10.51 and 8.534 μM, respectively. Furthermore, BP-1-102 inhibited the invasion and migration abilities of U251 and A172 cells by decreasing the expression of matrix metallopeptidase 9, and induced glioma cell apoptosis by decreasing the expression of B-cell lymphoma-2. BP-1-102 also inhibited the formation of neurosphere. Mechanically, BP-1-102 reduced the phosphorylation of STAT3 and the p-STAT3's nuclear translocation in glioma cells. Thus, this study herein provided a potential drug for glioma therapy.

To identify magnetic resonance imaging (MRI) features associated with injury type, severity, and liver transplantation (LT)/liver-related death (LRD) in drug-induced liver injury (DILI).The eligible DILI patients (2016 to 2020) who underwent contrast abdominal MRI within 3 months of onset were retrospectively analysed at Beijing Friendship Hospital, Capital Medical University. The MRI features independently associated with severity and prognosis were identified by backwards logistic regression. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) are given.The median age of 180 patients was 55.5 years, with 126 (70.0%) women. The injury types included hepatocellular (135 cases, 75.0%), mixed (23, 12.8%), and cholestatic (22, 12.2%). The proportion of periportal oedema in patients with hepatocellular and mixed injury was significantly higher than that in cholestatic injury (62.2%, 47.8% vs. 18.2%, p0.001). For severity, 157 (87.2%) patients had mild to moderate injury, and 23 (12.8%) had severe to fatal/LT. Irregularity of the liver surface (6.56 (95% CI, 1.27-22.84)), transient hepatic attenuation difference (THAD) (3.27 (95% CI, 1.14-9.36)), and splenomegaly (5.86 (95% CI, 1.96-17.53)) were independently associated with severity. Eight (4.4%) patients died/underwent LT. THAD (8.89 (95% CI, 1.35-58.43)), and ascites (64.63 (95% CI, 6.93-602.40)) were independently associated with LT/LRD. The prediction of the new model employing THAD and ascites for LT/LRD within 1 year was 0.959 (95% CI, 0.917-1.000).Periportal oedema was associated with the type of injury. Irregularity of the liver surface, THAD, and splenomegaly were associated with severity. THAD and ascites may have potential clinical utility in predicting LT/LRD outcomes within 1 year.• Contrast abdominal magnetic resonance imaging features can help clinicians evaluate the type of injury, severity, and poor prognosis of drug-induced liver injury. • Transient hepatic attenuation difference and ascites have potential clinical utility in the prediction of the poor prognosis of liver transplantation/liver-related death. • The new model predicting poor prognosis has a relatively high sensitivity of 0.875 and a high specificity of 0.919.

Major depressive disorder (MDD), particularly treatment-resistant ones, is associated with abnormal fronto-limbic glucose metabolism. 10-Hz repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex (PFC) is believed to normalize the abnormal metabolism to treat depression. However, the exact molecular mechanisms underlying the mood circuit of depressed brains and whether brain stimulation techniques regulate the underlying molecules remain elusive.Whole-brain glucose metabolism and cortical excitatory and inhibitory markers including P30, N45, P60, N100, and LICI (long-interval cortical inhibition) of TMS-evoked potentials from left DLPFC were measured in 40 subjects with MDD patients. The neurophysiological markers were repeated immediately after 1st session of left PFC rTMS, intermittent theta-burst stimulation (iTBS), and sham (randomly assigned).Brain glucose metabolism in the limbic structures significantly correlated with left PFC P30 (mainly GABA-A and glutamate receptor mediated) and with LICI (mainly GABA-B receptor mediated inhibition) (FWE-corrected p 0.001). Correlations between other neurophysiological markers (left PFC N45, P60, and N100) and posterior cingulate cortex, a key region in the default mode network, were also noted. One session of rTMS significantly decreased left PFC P60 (mainly glutamate receptor mediated), while a significant group effect was found for LICI (iTBS sham).The first study showed that the underlying molecular mechanisms of fronto-limbic circuit of MDD brains involved glutamatergic excitation and GABAergic inhibition at specific time points. In addition, one session of rTMS mainly modulated glutamatergic neurotransmission at left PFC, while the mechanisms of iTBS might involve GABA-B receptor mediated inhibition.UMIN000044951.

CrossFit® is a popular high-intensity functional training program. CrossFit® participants may practice popular diets or consume dietary and sports supplements to support their health or physical pursuits, but the specific dietary and supplement practices of CrossFit® participants remain unknown.An electronic questionnaire was developed to collect data on practice of popular diets (i.e. Paleo and The Zone Diet®), dietary and sports supplement use, reasons for practicing a diet or using supplements, sources of information on diets and supplements, and various beliefs associated with nutrition among CrossFit® participants.Of the 2,576 complete responses (female 51.9%, male 48.1%, age 39.4 ± 11.1 years, body mass index 26.1 ± 3.9 kg/mA large proportion of CrossFit® participants may practice popular diets or consume supplements with the intention of improving health or performance. These findings may support future research on the effects of various dietary patterns and supplements on CrossFit® performance.

Aim: Data are limited on PD-L1 expression and its association with overall survival (OS) in gastric cancer (GC) patients receiving routine care in different regions. Materials & methods: In a retrospective study, PD-L1 expression was assayed using the 22C3 pharmDx on GC tumor samples collected between 2003 and 2017 at South Korean and US cancer centers. PD-L1 positivity was defined as combined positive score (CPS) ≥1. The relationship between PD-L1 and OS was analyzed. Results: Of 574 GC tumor samples, 67.4% were CPS ≥1 (68.7% in Korean and 65.7% in US patients). PD-L1 expression was not associated with OS (adjusted hazard ratio: 0.94; 95% CI: 0.75–1.17). Conclusion: PD-L1 prevalence and its association with OS was similar between South Korean and US GC patients.

Proneural (PN) to mesenchymal (MES) transition (PMT) is a crucial phenotypic shift in glioblastoma stem cells (GSCs). However, the mechanisms driving this process remain poorly understood. Here, we report that Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key player in regulating PMT. FOSL1 is predominantly expressed in the MES subtype, but not PN subtype, of GSCs. Knocking down FOSL1 expression in MES GSCs leads to the loss of MES features and tumor-initiating ability, whereas ectopic expression of FOSL1 in PN GSCs is able to induce PMT and maintain MES features. Moreover, FOSL1 facilitates ionizing radiation (IR)-induced PMT and radioresistance of PN GSCs. Inhibition of FOSL1 enhances the anti-tumor effects of IR by preventing IR-induced PMT. Mechanistically, we find that FOSL1 promotes UBC9-dependent CYLD SUMOylation, thereby inducing K63-linked polyubiquitination of major nuclear factor κB (NF-κB) intermediaries and subsequent NF-κB activation, which results in PMT induction in GSCs. Our study underscores the importance of FOSL1 in the regulation of PMT and suggests that therapeutic targeting of FOSL1 holds promise to attenuate molecular subtype switching in patients with glioblastomas.

Purpose: Violent subjects were demonstrated to exhibit abnormal brain structures; however, the brain changes may be different between criminals committing affective (VA), predatory violence (VP), and non-violence (NV). Therefore, the purpose of this study was to compare the differences in brain structures and psychological characteristics between VA, VP, and NV offenders. Methods: Twenty male criminal subjects (7 VP; 6 VA; and 7 NV) offenders; and twenty age-matched male healthy non-criminals were enrolled in this study. All subjects received psychological assessments as well as magnetic resonance imaging scans of the brain. Analysis of variance (ANOVA) was performed to understand the differences among four groups with Bonferroni correction. The voxel-based morphometry and voxel-wise diffusion tensor imaging analyses were performed to compare the gray matter (GM) volume and white matter (WM) integrity between the groups. In significant regions, a Spearman correlation analysis was performed to understand the relationship between the brain changes and psychological scores. Results: The ANOVA analysis showed that AUDIT scores were significantly different among four groups, but no significant group difference was noted after Bonferroni correction. The imaging comparisons further demonstrated that the VP and NV offenders exhibited significant alterations of WM and GM tissues in the rectus and superior temporal gyrus, respectively. In addition, the VP offenders exhibited greater GM volumes than VA offenders in the right middle frontal gyrus, and NV offenders had greater GM volumes than VP offenders in the bilateral thalamus. Conclusion: We concluded that the VA, VP, and NV groups exhibited different degrees of alterations in GM and WM tissues in regions involved in emotion and cognition.

Mucosal healing, the result of endoscopic remission, is associated with prolonged clinical remission and delayed deterioration of Crohn's disease, which is significant and accompanied by reduced hospitalizations and surgeries. Currently, the relationship between ultrasonic parameters and mucosal healing remains controversial. To establish an ultrasonic regression model to evaluate mucosal healing, we conducted this preliminary study using multiple parameters from B-mode ultrasonography, colour Doppler flow imaging and shear wave elastography systematically.This study consisted of two single-centre investigations based on development and validation populations who received endoscopies (as the gold standard) and ultrasound. The involved bowel segments were divided into mucosal healing (MH) and nonmucosal healing (NMH) groups according to endoscopic results. Eight ultrasonic parameters were observed, including bowel wall thickness (BWT), mesenteric fat thickness (MFT), median modulus of elasticity (Emean), average shear wave velocity (SWV), Limberg scoring (LG), bowel wall stratification (BWS), ascites (AS) and lymph node enlargement (LN). We developed an ultrasonic regression model in the development phase to evaluate segmental mucosal healing and undertook prospective validation of this model.A total of 124 patients with 380 involved bowel segments from the development and validation cohorts were evaluated. Eight ultrasonic parameters were significantly different between the two groups (P0.05) in the development phase. Four significant parameters with better AUC performance were selected to establish an ultrasonic regression model to predict mucosal healing. The AUCs of this ultrasonic model were 0.975 and 0.942 in the development and validation cohorts, respectively.The multimodal ultrasonic model has the potential to evaluate segmental mucosal healing in Crohn's disease.

Background Pulmonary arterial hypertension (PAH) is a complex, fatal disease where disease severity has been associated with the single nucleotide polymorphism (SNP) rs2856830, located near the human leukocyte antigen DPA1 (HLA‐DPA1) gene. We aimed to define the genetic architecture of functional variants associated with PAH disease severity by identifying allele‐specific binding transcription factors and downstream targets that control endothelial pathophenotypes and PAH. Methods and Results Electrophoretic mobility shift assays of oligonucleotides containing SNP rs2856830 and 8 SNPs in linkage disequilibrium revealed functional SNPs via allele‐imbalanced binding to human pulmonary arterial endothelial cell nuclear proteins. DNA pulldown proteomics identified SNP‐binding proteins. SNP genotyping and clinical correlation analysis were performed in 84 patients with PAH at University of Pittsburgh Medical Center and in 679 patients with PAH in the All of Us database. SNP rs9277336 was identified as a functional SNP in linkage disequilibrium ( r 2 >0.8) defined by rs2856830, and the minor allele was associated with decreased hospitalizations and improved cardiac output in patients with PAH, an index of disease severity. SNP pulldown proteomics showed allele‐specific binding of nuclear ACTN4 (alpha actinin 4) protein to rs9277336 minor allele. Both ACTN4 and HLA‐DPA1 were downregulated in pulmonary endothelium in human patients and rodent models of PAH. Via transcriptomic and phenotypic analyses, knockdown of HLA‐DPA1 phenocopied knockdown of ACTN4, both similarly controlling cell structure pathways, immune pathways, and endothelial dysfunction. Conclusions We defined the pathogenic activity of functional SNP rs9277336, entailing the allele‐specific binding of ACTN4 and controlling expression of the neighboring HLA‐DPA1 gene. Through inflammatory or genetic means, downregulation of this ACTN4‐HLA‐DPA1 regulatory axis promotes endothelial pathophenotypes, providing a mechanistic explanation for the association between this SNP and PAH outcomes.

This study aimed to evaluate the effect of adjunctive melatonin supplementation on clinical outcomes after non-surgical periodontal treatment.PubMed, Embase, and Web of Science databases were systematically searched for randomised controlled trials (RCTs) of melatonin adjuvant therapy for periodontitis from inception until May 2021. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered on The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021250630). The risk of bias of included studies was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. The pooled effect estimates were calculated by a random-effects model, and results were expressed as weighted mean differences (WMD).Seven RCTs comprising 412 participants were included in the meta-analysis. The pooled results showed that adjuvant use of melatonin for non-surgical periodontal treatment significantly improved the probing depth (PD) [WMD = - 1.18, 95% CI (- 1.75, - 0.62) IWe found that adjunctive melatonin supplementation can significantly improve the periodontal status after non-surgical treatment, suggesting that melatonin may be a new adjuvant therapy for periodontitis when non-surgical periodontal treatment alone cannot achieve the desired improvement.

The relationship between toxic metals in the environment and clinical stroke risk remains unclear, although their role as immunotoxicants and carcinogens has been well established. We conducted a systematic review of the relationship between five metals (arsenic, mercury, copper, cadmium, and lead) and stroke. First, we comprehensively searched 3 databases (Pubmed, EMBASE, and Cochrane) from inception until June 2021. Random-effects meta-analyses, pooled relative risks (RR) and 95% confidence intervals (CI) were applied to evaluate the effect value. We finally identified 38 studies involving 642,014 non-overlapping participants. Comparing the highest vs. lowest baseline levels, chronic exposure to lead (RR = 1.07; 95%CI,1.00-1.14), cadmium (RR = 1.30; 95%CI,1.13-1.48), and copper (RR = 1.19; 95%CI,1.04-1.36) were significantly associated with stroke risks. However, the other two metals (arsenic and mercury) had less effect on stroke risk. Further analysis indicated that the association was likely in a metal dose-dependent manner. The results may further support the possibility that environmental toxic metal contaminants in recent years are associated with the increased risk of stroke.

Carpal tunnel release (CTR) is an effective procedure used in open, endoscopic, or ultrasound-guided methods. The complications are rare but potentially devasting. Most complications come from errors related to intraoperative technique, especially in the minimally invasive approach. An understanding of the "safe zones" is essential to perform percutaneous CTR safely. This article reviews the anatomy of safe zones and the ultrasound-guided CTR (UCTR) techniques in an attempt to prevent intraoperative complications. In strict accordance with the concepts of safe zones, UCTR is an effective and reliable procedure. Substantial experience for ultrasound-guided injection and surgery is required.

Lesinurad is a uricosuric agent for the treatment of hyperuricemia associated with gout, which was found lacking in efficacy and safety. Here, scaffold hopping and molecular hybridization were exploited to modify all the structural components of lesinurad, and 36 novel compounds bearing bicyclic imidazolopyridine core were obtained. In a mouse model of acute hyperuricemia, 29 compounds demonstrated increased serum uric acid (SUA)-reducing activity; SUA was treated with

Long-term unsolved health problems from pre-/intra-/postoperative complications and thermal ablation complications pose threats to liver-cancer patients. To reduce the threats, we propose a multimodal-imaging guided surgical navigation system and photothermal therapy strategy to improve specific labeling, real-time monitoring and effective treatment of hepatocellular carcinoma. Using a bioengineering approach, G-Nvs@IR820, a kind of human-cell-membrane nano-vesicle, was generated with growth arrest-specific 6 (Gas6) expressed on the membrane and with near-infrared absorbing dye (IR820) loaded into it, which is proven to be an effective nanoparticle-drug-delivery system for Axl-overexpressing hepatocellular carcinoma. G-Nvs@IR820 shows excellent features

Various hydrogels derived from the xenogeneic extracellular matrix (ECM) have been utilised to promote the repair and reconstruction of numerous tissues; however, there are few studies on hydrogels derived from allogeneic specimens. Human placenta derived hydrogels have been used in the therapy of ischaemic myocardium; however, their physicochemical properties and effects on cellular behaviour remain elusive. As the human placenta retains pro-angiogenic growth factors, it is hypothesized that the placenta hydrogels possess the potential to improve angiogenesis. In this study, a soluble decellularized human placenta matrix generated using a modified method could be stored in a powder form and could be used to form a hydrogel

Infection by Kaposi sarcoma-associated herpesvirus (KSHV) can cause severe consequences, such as cancers and lymphoproliferative diseases. Whole inactivated viruses (WIV) with chemically destroyed genetic materials have been used as antigens in several licensed vaccines. During KSHV productive replication, virus-like vesicles (VLVs) that lack capsids and viral genomes are generated along with virions. Here, we investigated the immunogenicity of KSHV VLVs produced from a viral mutant that was defective in capsid formation and DNA packaging. Mice immunized with adjuvanted VLVs generated KSHV-specific T cell and antibody responses. Neutralization of KSHV infection by the VLV immune serum was low but was markedly enhanced in the presence of the complement system. Complement-enhanced neutralization and complement deposition on KSHV-infected cells was dependent on antibodies targeting viral open reading frame 4 (ORF4). However, limited complement-mediated enhancement was detected in the sera of a small cohort of KSHV-infected humans which contained few neutralizing antibodies. Therefore, vaccination that induces antibody effector functions can potentially improve infection-induced humoral immunity. Overall, our study highlights a potential benefit of engaging complement-mediated antibody functions in future KSHV vaccine development. IMPORTANCE KSHV is a virus that can lead to cancer after infection. A vaccine that prevents KSHV infection or transmission would be helpful in preventing the development of these cancers. We investigated KSHV VLV as an immunogen for vaccination. We determined that antibodies targeting the viral protein ORF4 induced by VLV immunization could engage the complement system and neutralize viral infection. However, ORF4-specific antibodies were seldom detected in the sera of KSHV-infected humans. Moreover, these human sera did not potently trigger complement-mediated neutralization, indicating an improvement that immunization can confer. Our study suggests a new antibody-mediated mechanism to control KSHV infection and underscores the benefit of activating the complement system in a future KSHV vaccine.

To observe the effect of acupuncture therapy based on "gut-brain axis" on clinical manifestations and gastrointestinal symptoms of children with autism spectrum disorder (ASD).A total of 66 children with ASD were randomly divided into an observation group and a control group, 33 cases in each group. The control group was treated by routine rehabilitation training. On the basis of the control group, the observation group was treated with acupuncture based on "gut-brain axis", and the acupoints were Touwei (ST 8), Shenting (GV 24), Sishencong (EX-HN 1), Tianshu (ST 25), Zhongwan (CV 12), Zusanli (ST 36), etc. Both treatments were given once every other day, 3 times a week, 4 weeks as a course of treatment, consecutively for 3 courses. The scores of autism behavior checklist (ABC), TCM symptoms of gastrointestinal disease and childhood autism rating scale (CARS) were compared between the two groups before and after treatment, and the clinical efficacy was evaluated.After treatment, the scores of ABC, CARS and TCM symptoms of gastrointestinal disease in the two groups were lower than before treatment (On the basis of routine rehabilitation training, acupuncture therapy based on "gut-brain axis" is effective in treating ASD, which can relieve the clinical manifestations and gastrointestinal symptoms.

Falls represent an important adverse effect associated with knee osteoarthritis and result in a significant financial burden on the healthcare system. Therefore, identification of fall predictors is essential to minimize fall incidence. However, few studies have investigated falls and fall predictors, particularly focused on the fear of falls and proprioception. In this study, we investigated significant fall predictors in patients with knee osteoarthritis in Malang, Indonesia. Our findings may serve as useful guidelines to develop geriatric fall prevention programs. This cross-sectional survey using purposive sampling was performed between April and July 2021 and included 372 participants. We recorded the following data: sociodemographic and medical history questionnaire responses, visual analog scale scores, Hopkins falls grading scale scores, Fall Efficacy Scale-International scores, proprioception test findings, knee injury and osteoarthritis outcome score (KOOS), range of motion (ROM), chair stand test and the timed up and go test performance. Data were analyzed using the chi-square and t tests, and multivariate logistic regression to determine significant fall predictors. Multivariate logistic regression analysis showed a lower risk of falls in patients with better proprioception and ROM than in the other groups (odds ratio 0.55 vs 0.96). The risk of falls was higher in patients with higher KOOS symptoms, fear of falls, diagnosis of low back pain and diabetes mellitus, and increased body mass index than in the other groups (odds ratio 1.41, 2.65, 1.27, 3.45, and 1.10, respectively. Our study shows that knee proprioception and ROM serve as protective factors against falls, whereas KOOS symptoms, fear of falls, low back pain, diabetes mellitus, and body mass index were associated with a high risk of falls, with diabetes mellitus and fear of falls being the most significant risk factors. These findings may be useful to policy makers to develop a fall prevention program that can be implemented in community health care centers across Indonesia to deliver individualized, person-centered care and improve fall prevention strategies through a systematic process comprising evaluation, intervention, and monitoring to minimize fall risk.

Background Primary cutaneous gamma/delta T-cell lymphoma is aggressive, frequently presenting as multiple plaques, tumors, and/or subcutaneous nodules. Methods In this study, we conducted a retrospective study in a tertiary center in Taiwan to characterize this rare tumor. Results We identified six patients. Five presented with a solitary lesion, including two with clinical impression of epidermal inclusion cyst or lipoma. Two of four evaluable cases exhibited epidermotropism, with one mimicking Pautrier's microabscess. The neoplastic cells were pleomorphic and mostly medium to large-sized. In all cases, the neoplastic cells expressed TCR-γ and/or TCR-δ, with four coexpressing βF1. Two of these βF1+ cases co-expressed TCR-γ, but not TCR-δ (two different clones). All were negative for EBV, low stage, and treated with radiotherapy alone or combined chemotherapy and radiotherapy. In two patients, lymphoma relapsed in 3 and 7 months, respectively, with one patient died of the disease in 7 months. Four other patients were free of disease for 6-126 months. Conclusion PCGD-TCL cases in Taiwan are more commonly solitary, frequently with indolent courses. The two currently available TCR-δ clones alone might be insufficient to detect all tumors. This article is protected by copyright. All rights reserved.

Chinese people's pornography use is increasing and condomless sex is prevalent in pornography. However, both the relationship between pornography and condom use among Chinese adults and the mechanisms underlying this relationship are underexplored. This study examined how perceptions of pornography were associated with attitudes toward condom use through the mediating effect of gratification of sexual pleasure and safer sex communication apprehension, and how shared pornography use with a partner during sex moderated these relationships. A total of 658 participants (391 women and 267 men) aged 18-65 years and involved in a romantic relationship completed an online survey assessing pornography consumption, condom use, gratification of sexual pleasure, and safer sex communication apprehension. Results showed that expressive/erotic perceptions of pornography were associated with higher levels of gratification of sexual pleasure, which were, in turn, associated with more negative attitudes toward condom use. Expressive/erotic perceptions of pornography were also associated with lower levels of safer sex communication apprehension and lower levels of negative attitudes toward condom use. Higher levels of shared pornography use with a partner during sex strengthened the direct positive relationship between expressive/erotic perceptions of pornography and negative attitudes toward condom use. Higher levels of shared pornography use during sex also strengthened the positive relationship between expressive/erotic perceptions of pornography and gratification of sexual pleasure, and the negative relationship between expressive/erotic perceptions of pornography and safer sex communication apprehension, which in turn, were significantly associated with attitudes toward condom use. Implications for sexual health education and limitations are discussed.

Objective: To review evidence for intensive care unit (ICU) sleep improvement bundle use, identify preferred sleep bundle components and implementation strategies, and highlight the role for pharmacists in developing and evaluating bundle efforts. Data Sources: Multiple databases were searched from January 1, 1990, to September 1, 2021, using the MeSH terms sleep, intensive care or critical care, protocol or bundle to identify comparative studies evaluating ICU sleep bundle implementation. Study Selection and Data Extraction: Study screening, data extraction, and risk-of-bias evaluation were conducted in tandem. The ICU quality improvement literature and Institute for Healthcare Improvement bundle improvement guidance were also reviewed to identify recommended strategies for successful sleep bundle use. Data Synthesis: Nine studies (3 randomized, 1 quasi-experimental, 5 before-and-after) were identified. Bundle elements varied and were primarily focused on nonpharmacological interventions designed to be performed during either the day or night; only 2 studies included a medication-based strategy. Five studies were associated with reduced delirium; 2 studies were associated with improved total sleep time and 2 with improved patient-perceived sleep. Pharmacists were involved directly in 4 studies. Relevance to Patient Care and Clinical Practice: Sleep improvement bundles are recommended for use in all critically ill adults; specific bundle elements and ICU team member roles should be individualized at the institution/ICU level. Pharmacists can help lead bundle development efforts and routinely deliver key elements. Conclusions: Pharmacists can play an important role in the development and implementation of ICU sleep bundles. Further research regarding the relative benefit of individual bundle elements on relevant patient outcomes is needed.

Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval [CI] 0.74–0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73–0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice.

Populations exposed to bioaerosols over time in wastewater treatment plants (WWTPs) will be infected. Then, the reverse quantitative microbial risk assessment (QMRA) provides a quantitative framework for the estimation of acceptable exposure time to protect people from excessive exposure and then manage their health risk. In this study, the acceptable exposure time for staffs and visiting researchers exposed to S. aureus or E. coli bioaerosols emitted from aeration ponds in WWTPs was estimated and analyzed by Monte Carlo simulation-based reverse QMRA (using the 1E-4 pppy suggested by the US EPA or 1E-6 DALYs pppy suggested by the WHO as benchmarks). The 1E-3 and 1E-2 pppy were selected as a series of loose annual infection risk benchmarks to calculate a practical acceptable exposure time. The results showed that for the acceptable exposure time in each specific exposure scenario, the exposure of females was consistently 0.3-0.4 times longer than that of males; the exposure of staffs was 3.6-3.9 times shorter than that of visiting researchers; the exposures of populations in the rotating-disc aeration mode were consistently 6.3-6.6 and 2.8-3.1 times longer than those in the microporous aeration mode for S. aureus and E. coli bioaerosols, respectively. The acceptable exposure time with the use of personal protective equipment (PPE) was 33.4-35.0 times as long as that without PPE. The US EPA benchmark is stricter than the WHO benchmark with regard to the estimation of the acceptable exposure time of S. aureus or E. coli bioaerosols. The 1E-3 pppy is more appropriate and practical than the US EPA benchmark, but the 1E-2 pppy is notably too loose for health risk management. This research can assist managers of WWTPs to formulate a justified exposure time and develop applicable administrative and personal intervention strategies. The results can enrich the knowledge bases of reverse QMRA to elect a series of loose health-based target risk benchmarks for health risk management.

Placental hypoxic-ischemic pathology is one of the common causes for adverse outcomes. But there is no commonly accepted evaluation system on specific morphological and histopathological measures of the placenta.This study aims to systematically select several core placental hypoxic-ischemic measures that have a high prognostic relevance to child health.We used data from the Collaborative Perinatal Project, a multicenter prospective cohort study that recruited over 55,000 pregnant women and followed their offspring to 7 years old. Women who had information on placental pathology and child outcomes were included. 57 placental measures considered to be relevant to hypoxia-ischemia were selected. Apgar score, intelligence quotient, preeclampsia, birth weight and subclinical neurology injuries were chosen as outcomes. The least absolute shrinkage and selection operator (LASSO) procedure as well as training and testing methods were used to select a more efficient and simpler placental hypoxic-ischemic measures that may have clinical implications.Of the 57 measures, 7 were selected as candidates by LASSO. Based on the training and testing methods, we retained placental measures with a higher odds ratio of child morbidity. We further narrowed down to four measures that had the highest prognostic relevance. They were: short cord length (ΣOR = 8.51), calcification of cut surface (ΣOR = 8.31), opaque membranes (ΣOR = 5.26), Hofbauer cells in terminal villi (ΣOR = 4.69).Our four-measure system is relatively simple and closely related to the child health. It may be used as a novel placental hypoxic-ischemic evaluation criterion, and function as the first line tool for future research.

Background: Acute kidney injury (AKI) is the most frequent complication in critically ill neonatal and pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support. This study analyzed risk factors for in-hospital mortality and the incidence of AKI in neonatal and pediatric patients received ECMO support. Methods: We reviewed the medical records of 105 neonatal and 171 pediatric patients who received ECMO support at the intensive care unit (ICU) of a tertiary care university hospital between January 2008 and December 2015. Demographic, clinical, and laboratory data were retrospectively collected as survival and AKI predictors, utilizing the Kidney Disease Improving Global Outcome (KDIGO) consensus definition for AKI. Results: In the 105 neonatal and 171 pediatric patients, the overall in-hospital mortality rate were 58% and 55% respectively. The incidence of AKI at post-ECMO 24 h were 64.8% and 61.4%. A greater KDIGO24-h severity was associated with a higher in-hospital mortality rate (chi-square test; p

To observe the effect of electroacupuncture (EA) at back-A total of 72 patients with CFS were randomized into an EA group (36 cases, 4 cases dropped off) and a sham EA group (36 cases, 3 cases dropped off). In the EA group, EA at Ganshu (BL 18), Xinshu (BL 15), Pishu (BL 20), Feishu (BL 13) and Shenshu (BL 23) was adopted, with continuous wave, 2 Hz in frequency. In the sham EA group, sham EA at non-acupoints (1.5-2.0 cm lateral to back-After treatment, the physical fatigue score, mental fatigue score and total score of FS-14, as well as RMT of motor cortex in the EA group were decreased compared with those before treatment (EA at back

Background Ocular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS). Methods In total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA. Results In this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P P P = 0.020, and P P = 0.013). The OA blood velocity and mass flow ratio were correlated with several clinical parameters. Conclusions This study revealed morphological and hemodynamic differences in the OA between patients with T2D with and without ACS. Furthermore, the hemodynamic characteristics of the OA correlated with clinical prognostic biomarkers, suggesting the potential predictive ability of the OA.

Cardiomyocyte injury is a common complication during cardiac surgery with cardiopulmonary bypass (CPB). Studies have shown that circulating small extracellular vesicles (sEVs) are involved in the pathological process of cardiovascular diseases via delivering signaling molecules. This study aims to investigate the relationship between circulating sEV-encapsulated long noncoding RNAs (lncRNAs) and cardiac injury after CPB. Here, we found that the expression of sEV SEMA5A-IT1 in serum samples of patients after CPB was higher than that of pre-CPB serum samples. Moreover, serum-derived sEV SEMA5A-IT1 levels were negatively correlated with creatine kinase-MB (CK-MB) levels in patients who underwent CPB operation. Notably, circulating sEVs packaged with SEMA5A-IT1 could be uptaken by cardiomyocyte-like cells AC16 and increased SEMA5A-IT1 expression in AC16 cells. Upregulated SEMA5A-IT1 protected cardiomyocytes against hypoxia/reoxygenation injury, confirmed by increased cell viability, reduced cell apoptosis, and inhibited ferroptosis in AC16 cells. Mechanistically, SEMA5A-IT1 regulated the expression of B-cell CLL/lymphoma 2 (BCL2) and solute carrier family 7 member 11 (SLC7A11) through sponging miR-143-3p. Transfection of miR-143-3p mimics,BCL2, orSLC7A11knockdown could attenuate the protective effect of SEMA5A-IT1 on cardiomyocytes. In conclusion, we propose that SEMA5A-IT1, which is transported to cardiomyocytes through circulating sEVs, is an important regulatory molecule that protects cardiomyocytes from ischemia–reperfusion injury, providing a target for the prevention and treatment of myocardial ischemia–reperfusion injury.

The linear sequence of DNA provides invaluable information about genes and their regulatory elements along chromosomes. However, to fully understand gene function and regulation, we need to dissect how genes physically fold in the three-dimensional nuclear space. Here we describe immuno-OligoSTORM, an imaging strategy that reveals the distribution of nucleosomes within specific genes in super-resolution, through the simultaneous visualization of DNA and histones. We combine immuno-OligoSTORM with restraint-based and coarse-grained modeling approaches to integrate super-resolution imaging data with Hi-C contact frequencies and deconvoluted micrococcal nuclease-sequencing information. The resulting method, called Modeling immuno-OligoSTORM, allows quantitative modeling of genes with nucleosome resolution and provides information about chromatin accessibility for regulatory factors, such as RNA polymerase II. With Modeling immuno-OligoSTORM, we explore intercellular variability, transcriptional-dependent gene conformation, and folding of housekeeping and pluripotency-related genes in human pluripotent and differentiated cells, thereby obtaining the highest degree of data integration achieved so far to our knowledge.

The long noncoding RNA (lncRNA) THOR is highly conserved and expressed in various human cancer tissues, although its potential role and underlying mechanism in endometrial cancer (EC) remain unknown. This study aims to explore THOR's biological function and molecular mechanism in EC progression. THOR expression in EC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR) and in situ hybridization (ISH). THOR expression based on The Cancer Genome Atlas (TCGA) and clinical sample analyses was significantly higher in EC tissues than normal tissues, and higher THOR levels were closely associated with poor overall survival in EC. Additionally, a positive correlation between ISH-detected THOR expression and pathological grade was observed. CCK-8, colony formation, and transwell migration and invasion assays revealed that THOR significantly enhances the proliferation, migration, and invasion abilities of EC cells. Moreover, IGF2BP1 protein expression and ERK and AKT protein phosphorylation levels in EC cells increased significantly with THOR overexpression in EC cells. In conclusion, our findings suggest that THOR promotes EC cell growth and invasion, and IGF2BP1-mediated AKT and ERK signaling pathways activation might be involved. Clinically, THOR is significantly expressed in EC, and high THOR expression correlates with poor prognosis, making it a potential prognostic marker for EC.

Developing a community-based network by training peers as anti-drug ambassadors (ADAs) is a feasible strategy to identify hidden drug abusers. The Ask, Warn, Advise, Refer and Do-it-again (AWARD) model of smoking cessation is useful for enhancing people’s confidence in making referrals to anti-drug services. This study evaluated the effectiveness of such a network by examining the change in knowledge, attitudes and practices (KAP) of 198 ADAs aged 13–18 before and after six months of our training. A one-group pre-test and repeated post-test design was used. One-way repeated-measures analysis of variance was applied to assess the changes in KAP, with p-values adjusted by Bonferroni correction. The results showed that the ADAs statistically significantly improved their KAP regarding drug abuse at the six-month follow-up compared to baseline. All ADAs who knew drug abusers (n = 3) had referred them to services based on the AWARD model. A total of 154 anti-drug abuse activities were conducted, reaching 4561 people. Based on the results, we concluded that the community-based network was effective in improving the KAP of ADAs regarding drug abuse, as well as referring hidden drug abusers. Future studies should consider implementing the network on a larger scale, thus maximizing its anti-drug capacity.

The dissemination of the fact that the human papillomavirus (HPV) vaccine can protect females as well as males is greatly beneficial for the control of condyloma acuminata (CA). We aimed to investigate the acceptance of the HPV vaccine for CA among men who have sex with men (MSM) in China. A cross-sectional online survey in the adult MSM population from 31 regions in China was carried out via WeChat in May 2017. Information on demographic characteristics, sexual behaviors, history of HIV and HPV infection, awareness of CA and HPV/CA vaccines, acceptance of CA vaccination, and behavioral intentions for vaccination were collected through a self-administered questionnaire. In total, 902 questionnaires were analyzed; the prevalence of CA was 13.3% (120/902), the HIV positivity rate was 15.1% (136/902), and the coinfection rate of HIV and CA was 3.9% (35/902). In the MSM population, the knowledge of CA and HPV/CA vaccines was poor, but the acceptance rate of the CA vaccine was high (85.1%, 768/902). Data indicated that MSM who had a history of anal intercourse (OR = 1.9), had heard of CA (OR = 2.9), knew the treatments for CA (OR = 2.0), had heard of HPV vaccines/cervical cancer vaccines (OR = 1.9), and received education about CA (OR = 1.9) were associated with the intention to use CA vaccines. With current moderate levels of CA and HPV/CA vaccine awareness, more emphasis should be placed on improving education and other behavioral interventions for high-risk populations such as MSM in China.

Context A personalized antiplatelet therapy guided by a novel platelet function testing (PFT), PL-12, is considered an optimized treatment strategy in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy may differ in relation to diabetes status. Objective The aim of this study was to compare the outcomes of PFT-guided personalized DAPT in stable CAD patients with and without diabetes mellitus. Methods The PATH-PCI trial randomly assigned 2285 stable CAD patients to either personalized antiplatelet therapy or standard antiplatelet treatment. We investigated the association and interaction of diabetes on clinical outcomes across 2 treatment groups. Results We did not find a significant difference between the personalized group and the standard group in net adverse clinical events in either diabetes patients (10.3% vs 13.4%, P = .224) or in the nondiabetic group (3.1% vs 5.0%, P = .064). In diabetes patients (n = 646, 28.3%), the overall ischemic event rates were significantly low (6.8% vs 11.3%, HR = 0.586, 95% CI, 0.344-0.999, P = .049) and the bleeding event rates did not differ between the 2 groups (3.5% vs 3.3%, HR = 1.066, 95% CI, 0.462-2.458, P = .882). Similarly, in nondiabetic patients, the overall ischemic event rates were significantly low (1.8% vs 4.2%, HR = 0.428, 95% CI, 0.233-0.758, P = .006) and the bleeding event rates did not differ between the 2 groups (1.6% vs 0.9%, HR = 1.802, 95% CI: 0.719-4.516, P = .209). Conclusion The present study suggests that personalized antiplatelet therapy according to PFT can reduce ischemic events but not increase bleedings in stable CAD patients with or without diabetes who have undergone PCI.

Background Xanthomicrol is one of the methoxylated flavones and a promising cancer chemopreventive agent, but its anti-migration and anti-invasion ability on human hepatocellular carcinoma (HCC) remains unknown. Objectives This study aims to explore Xanthomicrol’s effects on migration and invasion ability of the human HCC Huh7 cell line. Methods Viability of Huh7 cells was measured by cell counting kit-8 (CCK8) assay. Cell apoptosis was assayed with flow cytometry analysis. The ability of migration and invasion of Huh7 cells was then detected through Transwell assays. Epithelial–mesenchymal transition (EMT)-related proteins were also detected through Western blot. Key findings Xanthomicrol inhibits the migration and invasion of Huh7 cells. The overexpression of Μu-opioid receptor (MOR) increases Huh7 cells’ proliferation and enhances migration and invasion ability, while xanthomicrol treatment decreases the expression of MOR. Moreover, xanthomicrol can reverse migration, invasion and EMT-related protein expression by overexpressed MOR. Conclusions These results suggest that xanthomicrol is a potential MOR antagonist, and it possesses potent anti-migration and anti-invasion ability on Huh7 cells.

To evaluate the effects of intravenous iodinated contrast medium (ICM) administration on the deterioration of renal function (DRF), new renal replacement therapy (RRT) induction and mortality of hospitalized acute kidney injury (AKI) patients. Adult hospitalized patients undergoing a contrast-enhanced or unenhanced CT scan within 7 days after AKI diagnosis from January 2015 to December 2019 were identified in this retrospective study. Propensity score matching was performed. Outcomes in 7 and 30 days after CT scan were compared between the contrast and non-contrast groups. Additional analyses were also performed in patients stratified by SCr levels at AKI diagnosis, times and time of CT scan, and in patients without chronic kidney disease or RRT requirement prior to CT scan. In total, 1172 pairs were generated after 1:1 propensity score matching from 1336 cases exposed to ICM and 2724 unexposed. No significant differences were found in the outcomes between the two groups: DRF, 7.8% vs 9.0% (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.62–1.11) in 7 days, 5.1% vs 5.4% (OR 0.93, 95%CI 0.64–1.34) in 30 days; new RRT induction, 2.3% vs 3.3% (OR 0.72,95%CI 0.43–1.18) in 7 days, 4.2% vs 4.5% (OR 0.95,95%CI 0.64–1.41) in 30 days; and mortality, 3.9% vs 4.8% (OR 0.83,95%CI 0.56–1.22) in 7 days, 9.0% vs 10.2% (OR 0.88,95%CI 0.68–1.15) in 30 days. Subset analyses showed similar results. Intravenous ICM administration during AKI duration did not increase the risks of DRF, new RRT induction, and mortality in 7 and 30 days after CT scan. • Intravenous ICM administration in hospitalized AKI patients does not increase the risks of deterioration of renal function, RRT induction, and mortality in 7 and 30 days after CT scan. • The effects of intravenous ICM on adverse outcomes are minimal even in AKI patients with high level of SCr values or multiple CT scans.

Background Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and a highly variable survival rate. Few studies have focused on outcomes in rural and urban groups while also evaluating underlying diseases and prehospital factors for OHCAs. Objective To investigate the relationship between the patient's underlying disease and outcomes of OHCAs in urban areas versus those in rural areas. Methods We reviewed the emergency medical service (EMS) database for information on OHCA patients treated between January 2015 and December 2019, and collected data on pre-hospital factors, underlying diseases, and outcomes of OHCAs. Univariate and multivariate logistic regression analyses were used to evaluate the prognostic factors for OHCA. Results Data from 4225 OHCAs were analysed. EMS response time was shorter and the rate of attendance by EMS paramedics was higher in urban areas (p 24-h survival (odds ratio [OR] = 1.437, 95% confidence interval [CI]: 1.179–1.761). Age (OR = 0.986, 95% CI: 0.979–0.993). EMS response time (OR = 0.854, 95% CI: 0.811–0.898), cardiac arrest location (OR = 2.187, 95% CI: 1.707–2.795), attendance by paramedics (OR = 1.867, 95% CI: 1.483–2.347), and prehospital defibrillation (OR = 2.771, 95% CI: 2.154–3.556) were independent risk factors for survival to hospital discharge, although the influence of an urban area was not significant (OR = 1.211, 95% CI: 0.918–1.584). Conclusions Compared with rural areas, OHCA in urban areas are associated with a higher 24-h survival rate. Shorter EMS response time and a higher probability of being attended by paramedics were noted in urban areas. Although shorter EMS response time, younger age, public location, defibrillation by an automated external defibrillator, and attendance by Emergency Medical Technician-paramedics were associated with a higher rate of survival to hospital discharge, urban area was not an independent prognostic factor for survival to hospital discharge in OHCA patients.

Objective Incorporating spatial analyses and online health information queries may be beneficial in understanding the role of Google relative search volume (RSV) data as a secondary public health surveillance tool during pandemics. Hence, this study identified COVID-19 clustering and defined the predictability performance of Google RSV models in clustered and non-clustered areas of the United States. Methods Getis-Ord General and local G statistics were used to identify monthly clustering patterns. Monthly country- and state-level correlations between new daily COVID-19 cases and Google RSVs were assessed using Spearman's rank correlation coefficients and Poisson regression models for the period of January to December 2020. Results Huge clusters involving multiple states were found, which resulted from various control measures in each state. This demonstrates the importance of state-to-state coordination in implementing control measures to tackle the spread of outbreaks. Variability in Google RSV model performances was found among states and time periods, possibly suggesting the necessity of utilizing different frameworks for Google RSV data in each state. Moreover, the sign of a correlation can be utilized to understand public responses to control and preventive measures, as well as in communicating risk. Conclusion COVID-19 Google RSV model accuracy in the United States may be influenced by COVID-19 transmission dynamics, policy-driven community awareness, and past outbreak experiences.

Background and Aim Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. Methods Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. Results This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as “high” quality, only 15% was classified as “moderate,” and 65% of outcomes were rated as “very low.” Conclusion Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.

Objective This meta-analysis was implemented to evaluate the association between hypoxia-inducible factor-1α (HIF-1α) C1772T/G1790A polymorphisms and susceptibility to head and neck cancer (HNC). Material and methods This meta-analysis has been registered on PROSPERO platform (CRD42021257309). The PubMed, Embase and Web of Science databases were searched to retrieve eligible published papers. STATA software was used to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the correlation strength. Results Our results demonstrated that the HIF-1α C1772T polymorphism was significantly related to an increased HNC risk (OR = 2.27, 95% CI = 1.17–4.42 for the homozygous model; OR = 11.53, 95% CI = 1.11–120.4 for the recessive model), especially in Caucasians (OR = 2.16, 95% CI = 1.09–4.27 for the homozygous model; OR = 2.28, 95% CI = 1.15–5.51 for the recessive model). Similarly, a remarkable correlation was discovered between the G1790A polymorphism and HNC risk (OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 58.05, 95% CI = 1.70–1985.77 for the recessive model). Moreover, in the subgroup analysis by source of controls, a statistically significant correlation was discovered in the population-based (PB) subgroup (OR = 9.43, 95% CI = 1.20–73.9 for allelic model; OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 3.22, 95% CI = 1.28–8.08 for the heterozygous model; OR = 7.83, 95% CI = 1.48–41.37 for the dominant model; OR = 58.05, 95% CI = 1.70–1985.8 for the recessive model) but not in the hospital-based (HB) subgroup. Conclusion Our study found that both HIF-1α C1772T and G1790A polymorphisms might be a higher risk of HNC, especially in the Caucasian group with the C1772T polymorphism.

Background Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. Methods We enrolled 193 SARS-CoV-2 infected subjects in Ningbo and Zhoushan, Zhejiang, China, from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of serum antibody immunoglobulin M (IgM) and IgG against SARS-CoV-2 using colloidal gold-labeled and enzyme-linked immunosorbent assays. Results Of those, 31 were asymptomatic SARS-CoV-2 carriers, 148 symptomatic COVID-19 patients, and 14 presymptomatic COVID-19 patients. Compared to symptomatic COVID-19 patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower level of C-reactive protein, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (7.5 vs. 25.5 days, P = 0.030). The proportion of those persistently seropositive for IgG against SARS-CoV-2 was higher in COVID-19 patients than in asymptomatic carriers (66.1% vs. 33.3%, P = 0.037). Viral load was higher in symptomatic patients than presymptomatic patients (P = 0.003) and asymptomatic carriers (P = 0.004). Viral shedding duration was longer in presymptomatic COVID-19 patients than in asymptomatic carriers (48.0 vs. 24.0 days, P = 0.002). Asymptomatic carriers acquired infection more from intra-familial transmission than did COVID-19 patients (89.0% vs. 61.0%, P = 0.028). In 4 familial clusters of SARS-CoV-2 infection, asymptomatic carriers were mainly children and young adults while severe COVID-19 was mainly found in family members older than 60 years with comorbidities. Conclusion Asymptomatic carriers might have a higher antiviral immunity to clear SARS-CoV-2 than symptomatic COVID-19 patients and this antiviral immunity should be contributable to innate and adaptive cellular immunity rather than humoral immunity. The severity of COVID-19 is associated with older age and comorbidities in familial clustering cases.

Introduction Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive. Methods We performed whole-exome sequencing for 40 primary tumors (PTs) and 61 metastases from 47 patients with lung cancer, of which 40 patients had paired PTs and metastases. The PT-metastasis genomic divergence, metastatic drivers, timing of metastatic dissemination, and evolutionary origins were analyzed using appropriate statistical tools and mathematical models. Results There were various degrees of genomic heterogeneity when comparing the paired primary and metastatic lesions or comparing metastases of different sites. Multiple metastasis-selected/enriched genetic alterations were found, such as MYC amplification, NKX2-1 amplification, RICTOR amplification, arm 20p gain, and arm 11p loss, and these results were were also featured in a meta-analysis cross-validated using an independent cohort from Memorial Sloan-Kettering Cancer Center database. To elucidate the metastatic seeding time, we applied a metastatic model and found 61.1% of the tumors were late dissemination, in which the metastatic seeding happened approximately 2.74 years before clinical detection. One exception was lymph node metastases whose dissemination time was relatively early. By analyzing the evolutionary origins, we reported that nonlymph node metastases were mainly seeded by the PT (87.5%) rather than the earlier colonized lymph node metastases. Conclusions Our results shed light on the molecular features that potentially drive lung cancer metastases. The distinct temporospatial pattern of disease progression revealed that lung cancer was susceptible to either late dissemination or indolent early lymph node metastases, leaving a potential time window to minimize metastases by early cancer detection.