Search

The cancer-testis antigen A-kinase anchor protein 3 (AKAP3) has been shown to have a strong association with breast cancer (BC). However, its role in BC progression received scant attention. We aimed to explore the prognostic implication of aberrant AKAP3 expression for a better knowledge of BC progression and improved treatment. AKAP3 expression was quantitated using tissue microarrays and immunohistochemistry (IHC). Cell viability, invasion, migration, apoptosis, and expressions of PTEN/PI3K/AKT/mTOR signaling components were assessed in AKAP3-overexpressed or si-AKAP3-transfected BC cells. Finally, elevated AKAP3 expression was observed in BC versus paracancerous tissues. BC patients with high AKAP3 expression showed a worse prognosis than low expression patients (

Background: Myocardial fibrosis after myocardial infarction (MI) has been considered a core factor in the deterioration of cardiac function. Previous studies have shown that miRNA plays an important role in various pathophysiological processes of the heart. However, the role of miRNA in myocardial fibrosis regulation after MI remains unclear. In the present study, we documented that miR-218-5p was significantly decreased in myocardial fibroblasts after MI. Methods: The miRNA expression profiles of MI were downloaded from GEO Datasets. The expression of a fibrosis-related gene in vivo and in vitro was analyzed by RT-PCR, western blotting, and immunohistochemical staining. Results: Total 7 up- and 9 downregulated common miRNAs were found in the two profiles. Among these common genes, miR-218-5p was downregulated in the MI mice. MiR-218-5p mediated the myocardial fibrosis in vivo and in vitro. Mechanistically, we found that GJA1 (CX43) may be the target of miR218-5p, and overexpressed CX43 can partly block the function of miR-218-5p in fibrosis inhibition. Conclusion: Our results suggested that miR-218-5p plays an important role in myocardial fibrosis after MI by targeting CX43. Thus, miR-218-5p promises to be a potential diagnosis and treatment of myocardial fibrosis after MI.

Background Massive hemoptysis due to aspergilloma is a rare but life-threatening complication. Bronchial artery embolization is recommended as a definitive treatment for massive hemoptysis. Polyvinyl alcohol is widely used in bronchial artery embolization. A very small number of studies have reported disrupted polyvinyl alcohol, which may cause ectopic embolism. Case presentation This case highlights an unusual phenomenon in which polyvinyl alcohol fragments appeared on pathological examination in a 61-year-old man, ethnic Han, with massive hemoptysis caused by aspergilloma for whom bronchial artery embolization failed. Lobectomy was carried out successfully. Hematoxylin and eosin stain provides clear images of polyvinyl alcohol fragments, while alpha-smooth muscle cell actin and cluster of differentiation-34 immunohistochemistry revealed their localization in bronchioles. Conclusion Thus far, only two cases of polyvinyl alcohol fragments in the lung have been reported, and the mechanism has not been elucidated. These two cases revealed no counter-indication for the use of polyvinyl alcohol. However, in some cases of off-target embolization causing fatal complications, such as stroke, paraplegia, and myocardial, polyvinyl alcohol fragmentation needs to be taken into consideration.

Circulating tumor DNA (ctDNA) is an ideal biomarker for cancer diagnosis based on liquid biopsy, so there is an urgent need for developing an efficient, rapid, and ultrasensitive detection method to meet clinical needs. In this paper, a novel surface-enhanced Raman scattering (SERS) microfluidic chip combined with a catalytic hairpin assembly (CHA) was proposed to detect two non-small cell lung cancer (NSCLC)-related ctDNA (TP53 and PIK3CA-Q546K) simultaneously. The chip consists of six channels for parallel detection. In the reaction region, the CHA reaction between HP

Stressful life events are significant risk factors for depression, and increases in depressive symptoms have been observed during the COVID-19 pandemic. The aim of this study is to explore the neural makers for individuals' depression during COVID-19, using connectome-based predictive modeling (CPM). Then we tested whether these neural markers could be used to identify groups at high/low risk for depression with a longitudinal dataset. The results suggested that the high-risk group demonstrated a higher level and increment of depression during the pandemic, as compared to the low-risk group. Furthermore, a support vector machine (SVM) algorithm was used to discriminate major depression disorder patients and healthy controls, using neural features defined by CPM. The results confirmed the CPM's ability for capturing the depression-related patterns with individuals' resting-state functional connectivity signature. The exploration for the anatomy of these functional connectivity features emphasized the role of an emotion-regulation circuit and an interoception circuit in the neuropathology of depression. In summary, the present study augments current understanding of potential pathological mechanisms underlying depression during an acute and unpredictable life-threatening event and suggests that resting-state functional connectivity may provide potential effective neural markers for identifying susceptible populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

In this work, a microfluidic chip using Au@SiO

Background Mitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients. Methods We enrolled 66 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between January 2019 and October 2019. Respiratory, hemodynamic and bedside echocardiographic parameters were recorded. Plasma mtDNA, procalcitonin, interleukin 6, and interleukin 8 levels were examined. Results Plasma mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with ALI [5.01 (3.38–6.64) vs 4.13 (3.20–5.07) log copies/µL, p 0.0172]. mtDNA levels were independently associated with mortality (hazard ratio, 3.2052; 95% CI 1.1608–8.8500; p 0.0253) and ALI risk (odds ratio 2.7506; 95% CI 1.1647–6.4959; p 0.0210). Patients with high mtDNA levels had worse outcomes, and post hoc tests showed significant differences in 28-day survival rates. Increased mtDNA levels were seen in patients with abdominal infection. Conclusions Increased plasma mtDNA levels within 24 h after admission were significantly associated with ALI incidence and mortality in septic patients.

Herein, we proposed a novel biosensor based on a high-density "hot spot" Au@SiO2 array substrate and rolling circle amplification (RCA) strategy for the ultrasensitive detection of CpG methyltransferase (M.SssI) activity. In the presence of M.SssI, the RCA process can be triggered, causing the augmentation of the single-stranded DNA (ssDNA) at the tail of the double-stranded DNA (dsDNA), and the ssDNA can be hybridized with numerous DNA probes labeled with Raman reporters in the next steps. Afterwards, the resultant ssDNA can be modified to the Au@SiO2 array substrate with the SERS enhancement factor of 7.49 × 106. The substrate was synthesized by using a monolayer SiO2 array to pick up the Au nanoparticle (AuNP) array and finite-difference time-domain (FDTD) simulation showed its excellent SERS effect. Particularly, the developed biosensor displayed a significant sensitivity with a broad detection range covering from 0.005 to 50 U mL-1, and the limits of detection (LODs) in PBS buffer and human serum were 2.37 × 10-4 U mL-1 and 2.51 × 10-4 U mL-1, respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects and breast cancer, prostate cancer, gastric cancer and cervical cancer patients were analyzed, and the reliability of the results was also confirmed by western blot (WB) experiments. Taking advantage of these merits, the proposed biosensor can be a very promising alternative tool for the detection of M.SssI activity, which is of vital importance in the early detection and prevention of tumors.

2-tert-butyl-1,4-benzoquinone (TBBQ) is the major oxidative product of tert-butylhydroquinone which is a widely used antioxidant in edible oils. The biotoxicity of TBBQ is a risk to human health, that the rapid and accurate monitoring of TBBQ is needed. Herein, a specific chromogenic reaction between TBBQ and polyethyleneimine (PEI) could generate adducts with maximum absorption at 478 nm. Amine groups of PEI are prone to link with TBBQ through Michael addition to form colored adducts. A colorimetric method for detecting TBBQ in edible oils was developed based on the aforesaid chromogenic reaction. The linear range for TBBQ was from 3.0 to 100.0 μg g

Circular DNA aptamers are powerful candidates for therapeutic applications given their dramatically enhanced biostability. Herein we report the first effort to evolve circular DNA aptamers that bind a human protein directly in serum, a complex biofluid. Targeting human thrombin, this strategy has led to the discovery of a circular aptamer, named CTBA4T-B1, that exhibits very high binding affinity (with a dissociation constant of 19 pM), excellent anticoagulation activity (with the half maximal inhibitory concentration of 90 pM) and high stability (with a half-life of 8 h) in human serum, highlighting the advantage of performing aptamer selection directly in the environment where the application is intended. CTBA4T-B1 is predicted to adopt a unique structural fold with a central two-tiered guanine quadruplex capped by two long stem–loops. This structural arrangement differs from all known thrombin binding linear DNA aptamers, demonstrating the added advantage of evolving aptamers from circular DNA libraries. The method described here permits the derivation of circular DNA aptamers directly in biological fluids and could potentially be adapted to generate other types of aptamers for therapeutic applications.

Objectives. Dexmedetomidine is widely used as an adjunct to general anesthesia. In this study, we evaluated the effects of perioperative dexmedetomidine infusion on postoperative analgesia in patients undergoing lateral thoracotomy for thoracic esophageal cancer. Methods. A total of 62 patients undergoing lateral thoracotomy for thoracic esophageal cancer were randomized to receive adjuvant therapy with either dexmedetomidine (0.5 μg/kg intravenous bolus injection for 10 min before induction of anesthesia, followed by continuous infusion of 0.2–0.4 μg/kg/h until the end of surgery, and 0.06 μg/kg/h for 5 days after surgery) or equal volumes of saline. Acute postoperative pain was treated with patient-controlled intravenous sufentanil and flurbiprofen axetil. The primary outcomes of this study were the numbers of analgesic requirements in the first postoperative 72 h. Results. Perioperative dexmedetomidine did not decrease the numbers of analgesic requirements in the first postoperative 72 h (dexmedetomidine group: 12.14 ± 4.76, saline group: 10.89 ± 5.66; p=0.367). Likewise, the groups did not differ with respect to total postoperative analgesic requirements, postoperative pain, perioperative inflammation, blood cell count, incidence of adverse events, surgical recovery (assessed at postoperative days 2 and 5 using the surgical recovery scale), length of hospital stay, hospital cost, incidence of chronic pain, or quality of life. Notably, dexmedetomidine had beneficial effects on decreasing intraoperative opioid consumption and improving postoperative sleep quality. Discussion. Perioperative dexmedetomidine has limited analgesic benefits in lateral thoracotomy for esophageal cancer when added to an opioid-based multimodal anesthetic regimen but can reduce opioid consumption.

Early life stress (ELS) can be very harmful to an individual’s wellbeing and brain development. It is well established that childhood maltreatment is a significant risk factor for depression. ELS is positively correlated with depressive symptoms both in major depression disorder patients and healthy individuals, but the cognitive and neural mechanisms underlying this association are still unclear. In the present study, we calculate the within/between-network connectivity in 528 college students, and Pearson correlation was performed to investigate the relationship between network measures and ELS. Additionally, the same method was applied to verify these results in another sample. Finally, mediation analysis was performed to explore the cognitive and neural mechanisms regarding the association between ELS and depression. Correlation analysis indicated that ELS was positively correlated with the within-network connectivity of the ventral attention network (VAN), the dorsal attention network (DAN), the salience network (SN), the somatosensory network (SMN) and the between-network connectivity of ventral attention network-dorsal attention network (VAN-DAN), ventral attention network- somatosensory network (VAN-SMN), and ventral attention network-visual network (VAN-VN). Validation results indicated that ELS is associated with the within-network connectivity of VAN and DAN. Mediation analysis revealed that attention bias and the within-network connectivity of VAN could mediated the relationship between ELS and depression. Both behavioral and neural evidence emphasize ELS’s influence on individual’s emotion attention. Furthermore, the present study also provides two possible mediation models to explain the potential mechanisms behind the relationship between ELS and depression.

Background Higher neuroticism personality trait individuals have more negative mood states, more sensitive to negative information, and higher risk of mental illness. Good emotion regulation ability play an important role in healthy psychological, social and physical outcomes. Previous studies have suggested that higher neuroticism individuals have a diminished ability to regulate emotion regulation. Up to now, few studies investigate the neural basis between neuroticism and emotion regulation. Method In present study, we want to explore the neuroticism and the activity of some brain regions and functional amygdala connectivity (psycho–physiological interaction [PPI]) in a cognitive reappraisal task. Thus, 160 healthy young participants were scanned during a cognitive reappraisal task. Results The results revealed that neuroticism scores showed a significant negative association with the activity of the dorsomedial prefrontal cortex (dmPFC), inferior frontal cortex and middle frontal cortex in regulation of negative emotion. PPI analyses revealed that neuroticism scores were negatively associated with amygdala–dmPFC connectivity in regulation of negative emotion. Limitation Only cognitive reappraisal were investigated in this study. Other emotion regulation strategies such as expressive suppression need to be explored in the future study. Conclusion These results may suggest that highly neurotic participants display diminished cognitive reappraisal and diminished control function of the dmPFC over the amygdala in regulation of negative emotion.

The efficacy and the safety of bortezomib-based chemotherapy were characterized in mantle cell lymphoma (MCL) patients.The PubMed, Cochrane Library, Clinical Key, Science Direct, Oxford Journals, and China National Knowledge Internet databases were searched up to 1 May 2019. The selected trials needed to match the inclusion criteria and be carried out to evaluate quality appraisal and the synthesis of efficacy and safety. The enrolled MCL patients using bortezomib-based chemotherapy or chemotherapy alone needed to have been compared. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were combined to evaluate the efficacy while serious adverse events (SAEs) (grade III-IV peripheral neuropathy, neutropenia, and infection) were used to evaluate the safety. The heterogeneity of the results were analyzed simultaneously.A total of 620 patients were enrolled across four studies in our meta-analysis, and the pooled results showed that the PFS [hazard ratio (HR)=0.66, 95% confidence interval (CI)=0.54-0.82; p=0.0001)] and OS (HR=0.73, 95% CI=0.55-0.96; p=0.03) of patients with bortezomib-based chemotherapy were better than those of patients with chemotherapy alone, unlike ORR (risk ratio=1.46, 95% CI=0.85-2.49; p=0.17), while SAEs were prominent in the combination group.MCL patients who are ineligible for transplant or high-dose chemotherapy could benefit from bortezomib-based chemotherapy.Mantle hücreli lenfoma (MCL) hastalarında Bortezomib bazlı kemoterapinin etkinliği ve güvenilirliğinin belirlenmesi.1 Mayıs 2019 tarihine kadar PubMed, Cochrane Kütüphanesi, Klinik Anahtar, Doğrudan Bilim, Oxford Dergileri ve Çin Ulusal Bilgi İnternet veritabanları araştırıldı. Seçilen çalışmaların dahil edilme kriterlerini karşılaması ve kalite, ve etkinlik ve güvenlik sentezi yapmış olması gerekiyordu. Çalışmaların bortezomib bazlı kemoterapi ile sadece kemoterapi kullanan MCL hastalarını karşılıyor olması gerekiyordu. Etkinliği değerlendirmek için genel yanıt oranı (ORR), ilerlemesiz sağkalım (PFS) ve genel sağkalım (OS) birleştirilirken, ciddi advers olaylar (SAE’ler) (3-4. düzey periferik nöropati, nötropeni ve enfeksiyon) güvenliği değerlendirmek için kullanıldı. Sonuçların heterojenliği aynı anda analiz edildi.Meta-analizimizde dört çalışmaya toplam 620 hasta dahil edilmişti ve toplu sonuçlarda PFS [tehlike oranı (HR)=0,66, %95 güven aralığı (CI)=0,54-0,82; p=0,0001)] ve OS (HR=0,73, %95 CI=0,55-0,96; p=0,03) ORR’den (risk oranı=1,46, %95 CI=0,85-2,49; p=0,17) farklı olarak bortezomib bazlı kemoterapi alan hastalarda, tek başına kemoterapi alan hastalardan daha iyi idi, SAE’ler ise kombinasyon grubunda daha belirgindi.Nakil veya yüksek doz kemoterapi için uygun olmayan MCL hastaları bortezomib bazlı kemoterapiden yarar görebilir.

Identification of new genetic pathways or molecular targets that sensitize cancer cells to chemotherapeutic drugs may improve the efficacy of current chemotherapy. Here, we report that downmodulation of UHRF1 (ubiquitin‐like with PHD and RING finger domains 1) in retinoblastoma (RB) cells increases the sensitivity to histone deacetylase (HDAC) inhibitors, augmenting apoptotic cell death. We found that UHRF1 depletion downregulates two redox‐responsive genes GSTA4 (glutathione S‐transferase α4) and TXN2 (thioredoxin‐2) in RB cells, and increases the basal level of intracellular oxidative stress. Antioxidant treatment significantly reduced both basal and HDAC inhibitor‐induced DNA damage and apoptosis in UHRF1‐depleted cells. Knockdown of GSTA4 or TXN2 sensitized RB cells to HDAC inhibitors, demonstrating that GSTA4 and TXN2 play key roles in redox homeostasis in RB cells and the susceptibility to HDAC inhibitor treatment upon UHRF1 depletion. In human primary RB, GSTA4 and TXN2 proteins were found to be mostly elevated along with high UHRF1 expression. In addition to augmentation of apoptosis in UHRF1‐depleted RB cells, we also show that UHRF1 downmodulation derepresses the expression of photoreceptor‐specific genes in RB cells in cooperation with a HDAC inhibitor MS‐275 and promotes neuron‐like differentiation. However, further investigation revealed that the enhanced growth‐inhibitory effects of MS‐275 in UHRF1‐depleted cells were still mainly due to robust apoptosis induction rather than differentiation‐mediated growth arrest. Consistent with our findings, UHRF1 depletion in RB cells increased the therapeutic efficacy of MS‐275 in murine orthotopic xenografts. These results provide a novel basis for potential benefits of UHRF1 targeting for RB treatment., This study presents two novel tumor‐promoting functions of UHRF1 in retinoblastoma (RB). UHRF1 regulates reactive oxygen species (ROS)‐detoxifying genes to counteract the accumulation of intracellular ROS and thereby protects the cells from histone deacetylase (HDAC) inhibitor‐induced apoptosis. On the other hand, UHRF1 participates in repression of photoreceptor differentiation as a corepressor in a multiprotein complex containing HDAC to repress photoreceptor‐specific genes in RB cells.

OBJECTIVE: To document the effect of surgical steps, including penile degloving, plate transection, dorsal plication, and fasciocutaneous coverage, in primary hypospadias repair on penile length. METHODS: A consecutive series of 209 prepubertal boys with primary hypospadias repair was included with the age ranged from 10 to 97 months (mean, 31.7 months). Intraoperative stretched penile length (SPL) was measured before operation (n=209), and after each step, namely penile degloving (n=152), plate transection (n=139), dorsal plication (n=170), and fasciocutaneous coverage (n=209). SPLs before and after each steps or the entire operation were analyzed. The SPL was compared between plate transection group and plate preservation group, dorsal plication group and non-plication group, and plate preservation with plication group and plate preservation without plication group, respectively. Differences of SPL between before and after each steps were analyzed with factors including neourethra length, rest dorsal penile length, rest ventral penile length, preoperative SPL, and the degree of penile curvature after penile degloving, with multivariate linear regression analysis. RESULTS: All the four steps resulted in SPL difference. The SPL increased after penile degloving and plate transection (P0.05). And there was significant difference in the increased length of SPL between patients with and without plate transection (P0.05). And there was no significant difference in increased length between patients with and without dorsal plication (P>0.05). When patients with plate transection were excluded, dorsal plication resulted in no significant difference on postoperative SPL (P>0.05). The increased length of SPL after penile degloving, dorsal plication, or cutanofascial coverage was not related to the neourethra length, the rest dorsal penile length, the rest ventral penile length, the preoperative SPL, and the degree of penile curvature (P>0.05). However, the neourethra length and preoperative SPL were the influencing factors for the increased length of SPL after plate transection (P

Highlights: • Field investigations of major pollutants along the coast of China were carried out. • The distributions of pollutants are correlated with specific industry sectors. • The distribution characteristics of pollutants varied in different climatic zones. • The ecological risks are affected by both climate and physicochemical properties. Abstract Coastal ecosystem health is of vital importance to human well-being. Field investigations of major pollutants along the whole coast of China were carried out to explore associations between coastal development activities and pollutant inputs. Measurements of target pollutants such as PFAAs and PAHs uncovered notable levels in small estuary rivers. The Yangtze River was identified to deliver the highest loads of these pollutants to the seas as a divide for the spatial distribution of pollutant compositions. Soil concentrations of the volatile and semi-volatile pollutants showed a cold-trapping effect in pace with increasing latitudinal gradient. The coastal ecosystem is facing high ecological risks from metal pollution, especially copper (Cu) and zinc (Zn), while priority pollutants of high risks vary for different kinds of protected species, and the ecological risks were influenced by both climate and physicochemical properties of environmental matrices, which should be emphasized to protect and restore coastal ecosystem functioning.

Japanese encephalitis is the main cause of viral encephalitis in Asia. In a previous single-arm vaccine trial, an inactivated chromatographically purified Japanese encephalitis Vero cell vaccine (CVI-JE; JEVACTM) was safe and immunogenic in 152 Thai children aged 1–3 years receiving a 2-dose primary immunization and booster dose 1 year later. We conducted a 5-year follow-up assessment of the persistence of the immune response the 144 children remaining in this cohort after first booster dose. Immunity was assessed by 50% plaque reduction neutralization test annually for up to 5 years post-booster. Seroprotection rates (95%CI) decreased from 100% (97.1–100) at 1 year post-booster to 93% (85.0–98.3) at 5 years post-booster. No serious vaccine-related adverse events or Japanese encephalitis infections were reported. A 2-dose primary immunization and booster 1 year later with CVI-JE provided long-lasting immunity in the majority of children.

To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis.A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups.The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.

To summarize the experience of using robotic surgery to treat midline cysts (MLC) of the prostate in pediatric patients with hypospadias, and to introduce and evaluate the initial outcome of seminal passage reconstruction via robot-assisted laparoscopy during the removal of symptomatic MLCs.We included a case series of 17 symptomatic MLCs with hypospadias. All patients received both genetic and fertility evaluation. MLCs were removed via robot-assisted laparoscopy and the seminal passage was reconstructed in 7 patients.Five patients were assessed as fertile as adults, while the other 12 were assessed as infertile. All 17 patients received robot-assisted laparoscopic surgery to remove MLCs, and 7 patients received reconstruction of the seminal passage. Patients were followed-up for 5-24 months; there were no serious adverse events except for 1 patient who experienced a single occurrence of epididymitis 7 months after reconstruction of the seminal passage. There were no significant cystic remnants in any of the patients upon ultrasonography and/or urethrography after surgery. Urethroscopy and vasography were performed in 2 patients after reconstruction; in both cases, unobstructed seminal passages were indicated.Reconstruction of the seminal passage is practical when carried out by robot-assisted techniques. Initial results indicated that the reconstruction operations were able to restore patency in the seminal duct in some of the patients. Fertility is the goal of this technique, and long-term follow-up is needed.

IntroductionNeutrophil extracellular traps (NETs) act as a critical trigger of inflammation and coagulation. We hypothesized that NETs are associated with septic hypercoagulability.Materials and MethodsIn total, 82 patients admitted with sepsis in the Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled between February 2017 and April 2018. Clinical and hematological parameters and thrombotic or hemorrhagic events were recorded. Blood samples were obtained to assess biomarkers of NET formation, including neutrophil elastase 2 (ELA2) and citrullinated histone H3, and endothelial-derived biomarker syndecan-1. Autophagy levels and their regulation pathway were also examined to explore their interaction with NETs.ResultSepsis patients with disseminated intravascular coagulation (DIC) showed significantly higher levels of NET formation [ELA2, 1,247 (86–625) vs. 2,039 (1,544–2,534), p < 0.0001; H3, 140 (47–233) vs. 307 (199–415), p < 0.0001]. NET formation was independently associated with DIC risk [ELA2, OR 1.0028, 95% CI, 1.0010–1.0045; H3, OR 1.0104, 95% CI, 1.0032–1.0176] and mortality [ELA2, HR 1.0014, 95% CI, 1.0004–1.0024; H3, HR 1.0056, 95% CI, 1.0008–1.0115]. The area under the curve value for ELA2 in predicting DIC occurrence was 0.902 (95% CI, 0.816–0.957), and that of H3 was 0.870 (95% CI, 0.778–0.934). Furthermore, biomarkers of NET formation, endothelial cells, and autophagy exhibited a significant correlation [ELA2 and Syn (r = 0.5985, p < 0.0001), LC3B (r = −0.4224, p < 0.0001); H3 and Syn (r = 0.6383, p < 0.0001), LC3B (r = −0.3005, p = 0.0061)].ConclusionIncreased NET formation is significantly associated with sepsis-induced DIC incidence and mortality in sepsis patients, revealing a significant relationship with the autophagy pathway.Clinical Trial Registrationchictr.org.cn, identifier ChiCTR-ROC-17010750.

Adenosine, as a naturally occurring nucleoside, plays an important role in human health maintenance. In recent years, many studies have shown that adenosine has the effect of cancer inhibition, and some of its analogs have been successfully marketed as anticancer drugs. This report mainly describes the anti-colon cancer activities and mechanism of a novel halogenated adenosine analog named 5'-bromodeoxyadenosine (5'-BrDA). As a result, 5'-BrDA concentration-dependently inhibited colon cancer cells proliferation, induced autophagy without disruption of lysosomal stability, and promoted autophagy-independently cellular mitochondrial apoptosis by increasing the accumulation of reactive oxygen species. Furthermore, 5'-BrDA inhibited the tumor growth of colon cancer in CT26 inbred mice without affecting the body weight in vivo. Collectively, the above-mentioned mechanisms contributed to the anticancer activity of 5'-BrDA. It is rare to discover novel anticancer adenosine analogs during the past couple of decades. We believe that our work will enrich the understanding of adenosine analogs, also, pave the way for adenosine analogs product based anticancer drug development.

To observe the analgesic effect of lever positioning manipulation combined with pulsed electric field on patients with lumbar disc herniation and the influence on serum IL-1β and TNF-α.From January 2018 to March 2019, 58 patients with lumbar disc herniation were included in the study, which were randomly divided into observation group and control group by digital table method. Observation group of 29 cases, including 16 males and 13 females, aged (38.03±11.29) years old, were treated with lever positioning manipulation combined with pulsed electric field. The 29 cases in control group, including 17 males and 12 females, aged (38.21±9.16) years old, were treated with pulsed electric field. Both groups of patients were treated 3 times a week, once every other day, 3 times as a course of treatment. After 2 courses of treatment, the two groups of patients were scored before and after treatment by the numeric rating scales (NRS);at the same time, the serum levels of IL-1β and TNF-α were measured before and after treatment.The NRS scores of observation group and control group were 4.21±1.76, 4.66±1.61 before treatment, and 1.28±0.84, 2.10±1.35 after treatment, respectively. The NRS scores of the observation group after treatment was significantly lower than that of the control group (The lever positioning manipulation combined with pulsed electric field has a good analgesic effect on patients with lumbar disc herniation, and it has a significant impact on the patient's serum IL-1β and TNF-α concentration, which can be used as a clinical guide. However, the synergistic effect of lever positioning technique combined with pulsed electric field and guidelines for clinical treatment need further research.

Aberrant and exclusive expression of chromatin regulators in retinoblastoma (RB) in contrast to terminally differentiated normal retina presents a unique opportunity of selective targeting for RB. However, precise roles of these chromatin regulators in RB development and their potential as therapeutic targets have not been defined thoroughly. Here, we report that targeting of disruptor of telomeric silencing 1-like (DOT1L), a histone H3K79 methyltransferase, sensitizes RB cells to chemotherapeutic drugs by impairing the DNA damage response and thereby potentiating apoptosis while it is largely inefficacious as a single-agent therapy. Moreover, we identified high mobility group AT-hook 2 (HMGA2) as a novel DOT1L target gene in RB cells and found that its aberrant expression is dependent on DOT1L. As HMGA2 depletion reduced CHK1 phosphorylation during DNA damage response and augmented the drug sensitivity in RB cells, our results suggested that DOT1L targeting has a dual role in chemosensitization of RB cells by directly interfering with the immediate involvement of DOT1L in early DNA damage response upon genotoxic insults and also by downregulating the expression of HMGA2 as a rather late effect of DOT1L inhibition. Furthermore, we provide the first preclinical evidence demonstrating that combined therapy with a DOT1L inhibitor significantly improves the therapeutic efficacy of etoposide in murine orthotopic xenografts of RB by rendering the response to etoposide more potent and stable. Taken together, these results support the therapeutic benefits of DOT1L targeting in combination with other chemotherapeutic agents in RB, with mechanistic insights into how DOT1L targeting can improve the current chemotherapy in an RB cell-selective manner.

Endoplasmic reticulum (ER) stress and autophagy dysfunction contribute to the establishment and progression of diverse pathologies. Proteolytic activation of the transcription factor nSREBP1 is induced under ER stress; however, little is known about how SREBP1 and its nuclear active form nSREBP1 influence autophagy and unfolded protein response (UPR) activation in osteosarcoma cells. Our research focused on the effect of SREBP1/nSREBP1 upon apoptosis and autophagy during ER stress and the molecular mechanisms involved. Here, we showed that nSREBP1 binds to the promoter of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and then regulates ER stress, cell growth, cell apoptosis, and autophagy through the PERK signaling pathway. nSREBP1 increased PERK gene expression and phosphorylation. nSREBP1 was further demonstrated to activate ER stress response through stimulatory effects on PERK signaling. Overexpression of SREBP1 increased its cleavage and release of nSREBP1; therefore, the effect of SREBP1 is achieved through the enhancement of the expression of nSREBP1. Overexpression of SREBP1/nSREBP1 amplifies PERK-associated cell cycle stagnation with G1 phase arresting, S phase reducing, and G2-M phase delaying. LV-SREBP1/nSREBP1 can also bolster PERK's ER stress-associated pro-apoptotic effects. LV-SREBP1/nSREBP1 and LV-PERK can activate autophagy in ER stress response, along with the overexpression of SREBP1/nSREBP1 and PERK. This resulted in amplification of PERK-related changes to cell proliferation and ER stress-mediated apoptosis and autophagy, with the biological effect of nSREBP1 relying on PERK, which makes up one of the three branches of the UPR signaling pathway. This study reveals important roles for SREBP1/nSREBP1 in PERK signaling under ER stress. Furthermore, nSREBP1, the nuclear active form of SREBP1, is able to robustly augment the effects of PERK. Description of the link between PERK and SREBP1/nSREBP1 function offers an improved understanding of the ER stress response and insight into the biological function of SREBP1/nSREBP1.

BackgroundChlamydia trachomatis(CT) infection is one of the most pervasive sexually transmitted infections and has high prevalence in urogenital and extra-urogenital sites among men who have sex with men (MSM). This study investigated anatomical site-specific prevalence and genotypes of CT among MSM recruited from three geographic areas in China.MethodsWe collected urine specimens and anorectal, pharyngeal swab specimens from 379 MSM. CT infection was identified using polymerase chain reaction and CT genotyping was determined by sequences of the ompA gene.ResultsThe results indicated that the overall prevalence of CT infection was 18.2% (95% confidence intervals [CIs], 13.9–22.5%) and significantly different between the cities (p = 0.048). The infection was most common at the anorectal site (15.6, 95%CIs 11.6–19.5%) followed by urethral (3.2, 95%CIs 1.4–5.0%) and oropharyngeal sites (1.6, 95%CIs 0.3–2.9%). Genotypes D and G were the most common CT strains in this population but genotype D was significantly predominated in Nanjing while genotype G was in Wuhan. No genotype related to lymphogranuloma venereum was found. CT infection was significantly related to the infection ofNeisseria gonorrhoeae(adjusted odds ratio [aOR] 14.27, 95%CIs 6.02–33.83,p p = 0.03).ConclusionThe high CT infection prevalence, particularly in the anorectal site, among MSM suggests the necessity to development an integrated CT screening and treatment program specifically focusing on this high-risk population. Surveillance of CT infections should be improved by including both infection and genotype based surveys into the current surveillance programs in China.

RNF6, a RING-type ubiquitin ligase, has been identified as an oncogene in various cancers but its role in multiple myeloma (MM) remains elusive. In the present study we first showed that the expression levels of RNF6 in MM were significantly elevated compared with the bone marrow cells of healthy donors. Overexpression of RNF6 in LP1 and PRMI-8266 MM cell lines promoted cell proliferation, whereas knockdown of RNF6 led to apoptosis of MM cells. Furthermore, we revealed that RNF6, as a ubiquitin ligase, interacted with glucocorticoid receptor (GR) and induced its K63-linked polyubiquitination. Different from current knowledge, RNF6 increased GR stability at both endogenous and exogenous contexts. Such an action greatly promoted GR transcriptional activity, which was confirmed by luciferase assays and by the increased expression levels of prosurvival genes including Bcl-xL and Mcl-1, two typical downstream genes of the GR pathway. Consistent with these findings, ectopic expression of RNF6 in MM cells conferred resistance to dexamethasone, a typical anti-myeloma agent. In conclusion, we demonstrate that RNF6 promotes MM cell proliferation and survival by inducing atypical polyubiquitination to GR, and RNF6 could be a promising therapeutic target for the treatment of MM.

As one of the most frequently diagnosed cancers, esophageal squamous cell carcinoma (ESCC) remains the leading cause of malignancy‐related death worldwide. Many studies have focused on the potential role of cancer cells in educating B cells during cancer progression. Here, we aim to explore the role of circulating exosomes from ESCC in the generation of two main regulatory B (Breg) subsets, including interleukin‐10+ Bregs (B10) and programmed cell death (PD)‐1high Bregs. Firstly, we observed an elevated percentage of B10 cells in peripheral blood of ESCC patients compared with healthy controls. Then we isolated and characterized exosomes from the peripheral blood of ESCC patients and an ESCC cell line. Exosomes from ESCC patients and the ESCC cell line suppressed the proliferation of B cells and induced the augmentation of B10 and PD‐1high Breg cells. By comparing the long non‐coding RNA and mRNA expression profiles in exosomes from ESCC patients or healthy controls, we identified a series of differentially expressed genes. Finally, we undertook gene annotation and pathway enrichment analyses on differentially expressed genes to explore the potential mechanism underlying the modulatory role of cancer exosomes in B cells. Our findings contribute to the study on B cell‐mediated ESCC immunosuppression and shed light on the possible application of exosomes in anticancer therapies.

Owing to the low abundance of microRNAs (miRNAs) in living tumor cells, the development of intracellular cancer-relevant miRNA stimuli-activatable photosensitizers (PSs) for accurate imaging and efficient photodynamic therapy (PDT) of tumors in vivo is extremely challenging. Herein, we engineered a tumor targeting and intracellular trace miRNA-activatable nanophotosensitizer Y-motif/FA@HyNP on the basis of an endogenous ATP-powered strand-displacement cascade amplification strategy, which was prepared by assembly of a quencher BHQ2-labeled Y-motif DNA structure (containing ATP-binding aptamer and target miRNA-binding complementary sequence) on the surface of folate (FA) and amine-functionalized hybrid micellar nanoparticles. We showed that the fluorescence emissions at both 555 and 627 nm were effectively inhibited due to BHQ2 in Y-motif/FA@HyNPs, leading to negligible PDT efficacy. Once Y-motif/FA@HyNPs were selectively internalized into tumor cells via FA-receptor-mediated endocytosis, the intracellular trace target miRNA initiated the dissociation of the BHQ2-terminated sequences from Y-motif/FA@HyNPs by means of abundant endogenous ATP-powered strand-displacement reactions, causing remarkable fluorescence enhancement and cascade amplification PDT. The activated dual-color fluorescence emissions at 555 and 627 nm were feasible to achieve real-time, highly sensitive, and specific imaging of trace target miRNA in living tumor cells. With the guidance of excellent imaging in living mice, Y-motif/FA@HyNPs exhibited the precise and efficient PDT of tumors as well as insignificant side effects in vivo. This work revealed the great potential of using an integration of receptor-mediated cell uptake and target-triggered recycling cascade amplification strategy to design early cancer-relevant stimuli-activatable PSs for both fluorescence imaging and PDT ablation of tumors in vivo, which could effectively facilitate the timeliness and precision of early cancer diagnosis and therapy.

As a common malignancy in women, cervical squamous cell carcinoma is a major cause of cancer-related mortality globally. Recent studies have demonstrated that long non-coding RNA (lncRNA) can function as potential biomarkers in cancer prognosis; however, little is known about its role in cervical cancer. In this study, we downloaded the gene expression profiles along with the clinical data of patients with cervical squamous cell carcinoma from The Cancer Genome Atlas. By applying bioinformatics analysis including random forest selection and Least Absolute Shrinkage and Selection Operator (LASSO) cox regression model along with 10-fold cross-validation, we constructed a 26-lncRNAs risk model that can be used to predict the overall survival of cervical squamous cell carcinoma. After that, Kaplan-Meier analysis combined with log-rank p test was applied to assess the predictive accuracy of the 26-lncRNAs risk model. Further analysis showed that the prognostic value of 26-lncRNAs risk model was independent of other clinicopathological factors. At last, lncRNAs in the model were put into gene ontology biological process enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways analysis, which suggested that these lncRNAs might contribute to cancer-associated processes such as cell cycle and apoptosis. This study indicated that lncRNAs signature could be a useful marker to predict the prognosis of cervical squamous cell carcinoma.

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLA(Glu)) project onto both medial prefrontal cortex glutamate (mPFC(Glu)) and GABA (mPFC(GABA)) neurons that locally innervate mPFC(Glu) neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLA(Glu) inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLA(Glu)→mPFC(GABA→Glu) circuit that controls the checking symptoms of OCD.

Osteosarcoma is the most common primary solid malignancy of the bone, and its high mortality usually correlates with early metastasis. In this study, we developed a risk score model to help predict metastasis at the time of diagnosis. We downloaded and mined four expression profile datasets associated with osteosarcoma metastasis from the Gene Expression Omnibus. After data normalization, we performed LASSO logistic regression analysis together with 10‐fold cross validation using the GSE21257 dataset. A combination of eight genes (RAB1,CLEC3B,FCGBP,RNASE3,MDL1,ALOX5AP,VMO1 and ALPK3) were identified as being associated with osteosarcoma metastasis. These genes were put into a gene risk score model, and the prediction efficiency of the model was then validated using three independent datasets (GSE33383, GSE66673, and GSE49003) by plotting receiver operating characteristic curves. The expression levels of the eight genes in all datasets were shown as heatmaps, and gene ontology gene annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. These eight genes play a role in cancer‐related biological processes, such as apoptosis and biosynthetic processes. Our results may aid in elucidating the possible mechanisms of osteosarcoma metastasis, and may help to facilitate the individual management of patients with osteosarcoma after treatment.

Emerging evidence has indicated that microRNAs (miRNAs) play an important role in cervical cancer (CC). However, the role of miRNA (miR)‐665 in cervical cancer remains unclear. The aim of the present study was to investigate the potential functions of miR‐665 in CC and to identify the underlying mechanisms of action. Herein, we show that miR‐665 was downregulated in CC tissues and cell lines, which is negatively correlated with tumor size, distant metastasis, advanced TNM stage and poor prognosis. Functionally, miR‐665 inhibited cell proliferation, migration and invasion and resistance of cisplatin for CC cells, as well as tumor growth. We validated that transforming growth factor beta receptor 1 (TGFBR1) was a direct target of miR‐665 and mediated the ERK/SMAD pathway. In addition, we identified miR‐665 as the competing endogenous RNA for long noncoding (lnc)‐DANCR. These observations suggested that lnc‐DANCR‐mediated miR‐665 downregulation regulates the malignant phenotype of CC cells by targeting TGFBR1 through the ERK/SMAD pathway, which may present a pathway for novel therapeutic stratagems for CC therapy.

MicroRNA (miRNA), as one of the ideal target biomarker analytes, plays an essential role in biological processes; thus, the development of rapidly sensitive detection methods is imperative. Herein, we proposed a pump-free surface-enhanced Raman scatting (SERS) microfluidic chip for the rapid and ultrasensitive detection of miR-106b and miR-196b, laryngeal squamous cell carcinoma (LSCC)-related miRNAs. Ag-Au core-shell nanorods (Ag-AuNRs) were applied to prepare SERS tags by modifying Raman reporters and hairpin DNAs. The capture probes were synthesized by labeling hairpin DNAs onto the magnetic beads (MBs) surface. In the presence of targets, the catalytic hairpin assembly (CHA) reactions between SERS tags and capture probes could be triggered, causing the aggregation of Ag-AuNRs. The tiny magnets installed under the rectangular chamber could magnetically gather the CHA products, leading to the further aggregation of Ag-AuNRs. Thus, this strategy could achieve the double aggregation of Ag-AuNRs, resulting in the significant amplification of the SERS signal. The proposed strategy achieved simultaneous and sensitive detection of miR-106b and miR-196b, with limits of detection low to aM level. The whole detection process could be completed within 5 min. Moreover, this microfluidic chip exhibited excellent reproducibility, stability, and specificity. The high accuracy of this SERS microfluidic chip was proved by practical analysis in LSCC patients' serum. The results demonstrated that SERS could be a promising alternative clinical diagnosis tool and exhibited potential application for the dynamic monitoring of cancer staging.

Circular RNA 40S ribosomal protein S28 (circRPS28; hsa_circ_0049055) is upregulated in papillary thyroid carcinoma (PTC) patients. However, its role remained uncovered in the progression of PTC. Above all, expression of circRPS28 was determined in PTC samples by real-time quantitative PCR and circRPS28 was highly expressed in tumor tissues and cells. Besides, circRPS28 was predominantly distributed in the cytoplasm. Functional experiments were launched using colony formation assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2-deoxyuridine (EdU) assay, transwell assays, scratch wound assay, and flow cytometry. As a result, blocking circRPS28 restrained PTC cell viability, EdU positive cell rate, colony formation number, wounding healing rate, and numbers of migration and invasion cells, accompanied with apoptosis rate promotion. These effects paralleled with low B-cell lymphoma (Bcl)-2 level and high Bcl-2-associated X protein (Bax), matrix metalloproteinase-2 (MMP2), and MMP9 levels, as analyzed by western blotting. Overexpressing microRNA (miR)-345-5p exerted similar roles to circRPS28 silencing. Notably, dual-luciferase reporter assay and RNA immunoprecipitation confirmed the target relationship between circRPS28 and miR-345-5p, miR-345-5p and frizzled family receptor 8 (FZD8). Downregulating miR-345-5p abrogated effects of circRPS28 blockage in PTC cells, and restoring FZD8 counteracted miR-345-5p roles, either. Furthermore, xenograft tumor model was established in mice, and exhausting circRPS28 delayed the growth of PTC cells in vivo by regulating miR-345-5p and FZD8. In conclusion, we demonstrated that blocking circRPS28 and/or promoting miR-345-5p suppressed PTC cell growth and motility via regulating FZD8. This study might suggest a novel circRPS28/miR-345-5p/FZD8 competing endogenous RNA pathway in PTC.

An innovative surface-enhanced Raman spectroscopy and lateral flow assay (SERS-LFA) biosensor combined with aptamer recognition had been developed for the convenient, rapid, sensitive and accurate detection of thrombin and platelet-derived growth factor-BB (PDGF-BB) associated with prostate cancer simultaneously. During the biosensor operation, thrombin and PDGF-BB in the sample were recognized and combined by thiol-modified aptamers immobilized on Au-Ag hollow nanoparticles (Au-Ag HNPs) surface and biotinylated aptamers immobilized on the test lines of the biosensor. Thus, thrombin and PDGF-BB were simultaneously captured between detection aptamers and capture aptamers in a sandwich structure. Finite difference time domain simulation confirmed that 'hot spots' appeared at the gaps of Au-Ag HNPs dimer in the enhanced electromagnetic field compared to that of a single Au-Ag HNP, indicating that the aggregated Au-Ag HNPs owned a good SERS signal amplification effect. The detection limits of thrombin and PDGF-BB in human plasma were as low as 4.837 pg ml-1and 3.802 pg ml-1, respectively. Moreover, the accuracy of the biosensor which was applied to detect thrombin and PDGF-BB in prostate cancer plasma had been verified. This designed biosensor had broad application prospects in the clinical diagnosis of prostate cancer.

Increased anxiety in response to the COVID-19 pandemic has been widely noted. The purpose of this study was to test whether the prepandemic functional connectome predicted individual anxiety induced by the pandemic.Anxiety scores from healthy undergraduate students were collected during the severe and remission periods of the pandemic (first survey, February 22-28, 2020, N=589; second survey, April 24 to May 1, 2020, N=486). Brain imaging data and baseline (daily) anxiety ratings were acquired before the pandemic. The predictive performance of the functional connectome on individual anxiety was examined using machine learning and was validated in two external undergraduate student samples (N=149 and N=474). The clinical relevance of the findings was further explored by applying the connectome-based neuromarkers of pandemic-related anxiety to distinguish between individuals with specific mental disorders and matched healthy control subjects (generalized anxiety disorder, N=43; major depression, N=536; schizophrenia, N=72).Anxiety scores increased from the prepandemic baseline to the severe stage of the pandemic and remained high in the remission stage. The prepandemic functional connectome predicted pandemic-related anxiety and generalized to the external sample but showed poor performance for predicting daily anxiety. The connectome-based neuromarkers of pandemic-related anxiety further distinguished between participants with generalized anxiety and healthy control subjects but were not useful for diagnostic classification in major depression and schizophrenia.These findings demonstrate the feasibility of using the functional connectome to predict individual anxiety induced by major stressful events (e.g., the current global health crisis), which advances our understanding of the neurobiological basis of anxiety susceptibility and may have implications for developing targeted psychological and clinical interventions that promote the reduction of stress and anxiety.

Objective While the upregulation of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene expression has been reported in colon cancer, its role in tumorigenesis remains largely unknown. In this study, we aimed to investigate the involvement of CYP24A1 in Wnt pathway regulation via the nuclear factor kappa B (NF-κB) pathway. Methods The human colon cancer cell lines HCT-116 and Caco-2 were subjected to stimulation with interleukin-6 (IL-6) as well as tumor necrosis factor alpha (TNF-α), with subsequent treatment using the NF-κB pathway-specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). Furthermore, CYP24A1 expression was subjected to knockdown via the use of small interfering RNA (siRNA). Subsequently, NF-κB pathway activation was determined by an electrophoretic mobility shift assay, and the transcriptional activity of β-catenin was determined by a dual-luciferase reporter assay. A mouse ulcerative colitis (UC)-associated carcinogenesis model was established, wherein TNF-α and the NF-κB pathway were blocked by anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides, respectively. Then the tumor size and protein level of CYP24A1 were determined. Results IL-6 and TNF-α upregulated CYP24A1 expression and activated the NF-κB pathway in colon cancer cells. PDTC significantly inhibited this increase in CYP24A1 expression. Additionally, knockdown of CYP24A1 expression by siRNA could partially antagonize Wnt pathway activation. Upregulated CYP24A1 expression was observed in the colonic epithelial cells of UC-associated carcinoma mouse models. Anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides decreased the tumor size and suppressed CYP24A1 expression. Conclusion Taken together, this study suggests that inflammatory factors may increase CYP24A1 expression via NF-κB pathway activation, which in turn stimulates Wnt signaling.

Polyfluoroalkyl substances (PFASs) enter the environment through multi-media diffusion and long-distance migration during the long-term manufacture and use of products containing PFASs. This study analyzed 17 PFASs in surface water samples collected from the Wuliangsuhai watershed in the wet and dry seasons, and investigated the temporal and spatial distribution characteristics, potential sources, and ecological risks of PFASs in the study area. PFASs were detected in all surface water samples at concentrations ranging from 4.00 to 263.45 ng·L

To observe the clinical effect of lever positioning manipulation for the treatment of lumbar disc herniation and its effect on Cobb angle.From December 2017 to November 2018, 67 patients with lumbar disc herniation were included in the study. The patients were randomly divided into treatment group and control group by digital table method. There were 34 cases in the treatment group, including 20 males and 14 females, with an average age of (36.09±8.26) years old and a course of (13.79±15.50) months. Treatment group was treated with lever positioning manipulation. There were 33 cases in the control group, including 18 males and 15 females, with an average age of(36.48±7.81) years old and a course of (12.82±15.68) months. Control group was treated with lumbar slanting manipulation. Two groups were treated 3 times a week, once every other day, 6 times for a course of treatment, after 2 courses of treatment, the changes of Cobb angle before and after treatment were compared between two groups by imaging. The symptoms and signs were scored with reference to clinical evaluation standard;overall efficacy was evaluated with reference to "Diagnostic Efficacy Criteria of Traditional Chinese Medicine Syndrome" issued by the State Administration of Traditional Chinese Medicine for lumbar disc herniation.One patient in each group dropped out. The symptom and sign scores of treatment group and control group before treatment were 18.56± 4.81, 18.61±3.72, while after treatment were 9.41±5.19, 13.55±3.68;treatment group was significantly lower than control group after treatment (Both the lever positioning manipulation and the lumbar slanting manipulation methods are effective for the treatment of lumbar disc herniation, but clinical effect of lever positioning method on lumbar disc herniation is more significant, and the effect on Cobb angle is more obvious. It is worthy of promotion.

To determine whether brief ultrasound-guided treatment of hemodynamic shock and respiratory failure immediately before emergency noncardiac surgery reduced 30-day mortality.Parallel, nonblinded, randomized trial with 1:1 allocation to control and intervention groups.Twenty-eight major hospitals within China.Six-hundred sixty patients ≥14 years of age, scheduled for emergency noncardiac surgery with evidence of shock (heart rate120 beat/min, systolic blood pressure90 mmHg or requiring inotrope infusion), or respiratory failure (Pulse Oxygen Saturation92%, respiratory rate20 beat/min, or requiring mechanical ventilation).A brief (15 minutes) focused ultrasound of ventricular filling and function, lung, and peritoneal spaces, with predefined treatment recommendation based on the ultrasound was performed before surgery or standard care.The primary outcome was 30-day mortality. Secondary outcomes included changes in medical or surgical diagnosis and management due to ultrasound, intensive care unit, and hospital stay and cost, and Short Form-8 quality-of-life scores. Although there were frequent changes in diagnosis (82%) and management (49%) after the ultrasound, mortality at 30 days was not different between groups (50 [15.7%] v 53 [16.3%]; odds ratio 1.05, 0.69-1.6, p = 0.826). There were no differences in the secondary outcomes of the days spent in the hospital (mean 13.8 days, 95% confidence interval [CI] 12.1-15.6 v 14.4 d, 11.8-17.1, p = 0.718) or intensive care unit (mean 9.3 days, 95% CI 7.7-11.0 v 8.7 d, 7.2-10.2, p = 0.562), hospital cost (USD$14.5K, 12.2-16.7 v 13.7, 11.5-15.9, p = 0.611) or Short Form-8 scores at one year (mean 80.9, 95% CI 78.4-83.3 v 79.7, 76.9-82.5, p = 0.54) between participants allocated to the ultrasound and control groups.In critically ill patients with hemodynamic shock or respiratory failure, a focused ultrasound-guided management did not reduce 30-day mortality but led to frequent changes in diagnosis and patient management.

Objective: To investigate the differences in imaging characteristics and the diagnostic accuracy of 225 intraosseous jaw lesions on panoramic radiographs (PAN) versus cone beam computed tomography (CBCT). Methods: 225 sets of PAN and CBCT images with biopsy-proven histopathological diagnoses were retrospectively compared in terms of radiographic features and diagnostic accuracy. The imaging characteristics of PAN and CBCT were independently evaluated by two oral and maxillofacial radiologists who were required to answer 12 questions and provided up to three differential diagnoses with their confidence scores. Results: Odds ratios (ORs) were statistically significant for border cortication (OR = 1.521; p = .003) and border continuity (OR = 0.421; p = .001), involvement on neurovascular canals (OR = 2.424; p < .001), expansion (OR = 7.948; p < .001), cortical thinning (OR = 20.480; p < .001) as well as its destruction (OR = 25.022; p < .001) and root resorption (OR = 2.477; p < .001). Furthermore, imaging features in the posterior and mandibular regions showed better agreement than those in the anterior and maxillary regions, respectively. The diagnostic accuracy of the first differential diagnosis was higher on CBCT than on PAN (Observer 1:78.7 vs 64.4%; Observer 2: 78.7 vs 70.2% (p < .001)). The observers’ confidence scores were also higher at CBCT interpretation compared with PAN. Conclusions: CBCT demonstrated a greater number of imaging characteristics of intraosseous jaw lesions compared with PAN, especially in the anterior regions of both jaws and in the maxilla. Diagnostic accuracy is improved with CBCT compared to PAN, especially for lesions in the maxilla. Radiologists have greater confidence when using CBCT.

Creative thinking is a hallmark of human cognition, which enables us to generate novel and useful ideas. Nevertheless, its emergence within the macro-scale neurocognitive circuitry remains largely unknown. Using resting-state fMRI data from two large population samples (SWU: n = 931; HCP: n = 1001) and a novel “travelling pattern prediction analysis”, here we identified the modularized functional connectivity patterns linked to creative thinking ability, which concurrently explained individual variability across ordinary cognitive abilities such as episodic memory, working memory and relational processing. Further interrogation of this neural pattern with graph theoretical tools revealed both hub-like brain structures and globally-efficient information transfer paths that together may facilitate higher creative thinking ability through the convergence of distinct cognitive operations. Collectively, our results provide reliable evidence for the hypothesized emergence of creative thinking from core cognitive components through neural integration, and thus allude to a significant theoretical advancement in the study of creativity.

Transforming growth factor-β1 (TGF-β1) signaling pathway has been implicated in the fibroblast activation of hypertrophic scarring (HS). Previously, we proposed a new biotherapeutic strategy to combat HS by disrupting the intermolecular interaction of TGF-β1 with its cognate type-II receptor (TβR-II). Here, we further demonstrate that the binding site of TGF-β1 to TβR-II is not overlapped with the conformational wrist epitope and linear knuckle epitope that are traditionally recognized as the functional binding sites of bone morphogenetic protein-2 (BMP-2) to its type-II receptor (BMPR-II), which can thus be regarded as a new functional site we called elbow epitope. Structural, energetic, and dynamic investigations reveal that the elbow epitope consists of two sequentially discontinuous, spatially vicinal segments Loop30-34 and Turn90-95 ; they cannot work effectively to independently interact with TβR-II. Rational redesign of the epitope is performed using an integrated in silio-in vitro method based on crystal and modeled structure data. In the procedure, the two epitope segments are split from the interface of TGF-β1-TβR-II complex and then connected with each other in a head-to-tail manner by adding a flexible poly-(Gly)n linker between them, thus resulting in a series of combined peptides. We found that the peptide affinity reaches maximum at n = 2, which shares a consistent binding mode with the elbow epitope at native complex interface. The linker of either too long (n > 2) or too short (n < 2) cannot properly place the gap space between the two segments, thus impairing the binding compatibility of designed peptides with TβR-II active site.

Timing can be processed explicitly or implicitly. Temporal orienting is a typical implicit timing through which we can anticipate and prepare an optimized response to forthcoming events. It is, however, not yet clear whether mechanisms such as temporal-pulse accumulation and attentional gating (more attention, more accumulated temporal pulses) underly the internal representations of temporal orienting, as in explicit timing. To clarify this, a dual-task paradigm, consisting of a temporal orienting and an interference task, was adopted. Consistent with the temporal-pulse-accumulation and attentional-gating model, reaction times to the target detection of temporal orienting increased as the interference stimuli were temporally closer to the target, i.e., a location effect for temporal orienting. This effect is likely due to attention being diverted away from temporal orienting to monitor the occurrence of the interference stimuli for a longer time, resulting in greater temporal pulse loss and less accurate temporal orienting for conditions with later interference stimuli. The temporal-pulse-accumulation aspect in temporal orienting received further support by taking an explicit duration reproduction (containing a second temporal-pulse accumulation) as the interference task. On the one hand, temporal orienting became less accurate with increased temporal-pulse-accumulation overlaps between the dual tasks; on the other hand, two-way (one for temporal orienting and the other for duration reproduction), rather than one-way, location effects were observed, implying processing conflicts between the two temporal-pulse accumulations. Taken together, these results suggest that implicit and explicit timing may share common mechanisms upon internal temporal representations.

The feasibility and prognostic value of quantitative flow ratio (QFR) after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients have not been assessed. The aim of this study was to investigate the prognostic utility of post-PCI QFR to predict outcomes in STEMI and determine the influence of functional results, in both culprit and nonculprit lesions, after PCI. Patients undergoing PCI of culprit lesions and receiving staged procedures of nonculprit lesions after 7 days were enrolled from 2 centers and underwent post-PCI QFR. The primary outcome was the vessel-oriented composite endpoints (VOCEs), defined as vessel-related cardiovascular death, vessel-related myocardial infarction, and target vessel revascularization. Four hundred fifteen vessels (186 culprit lesions and 219 nonculprit lesions) in 186 patients were analyzed. Measured at staged PCI, the post-PCI QFR of culprit lesions was significantly lower than that of nonculprit lesions (0.92 ± 0.10 versus 0.95 ± 0.08, p

Negative-pressure wound therapy is widely used in burn populations. Traditionally, negative-pressure devices use persistent vacuum suction, requiring a longer hospital stay. In this study, we applied a novel negative-pressure wound dressing for burn wounds, which eliminates the hospital stay. The medical records of 39 patients with partial-/full-thickness burns treated by negative-pressure wound dressing were retrospectively analyzed. The average burn area, burn degree, healing duration, cost, and incidents during treatment were determined and compared with previous data for conventional therapies. In conclusion, for patients diagnosed with partial-thickness or full-thickness burns and a burn area 2, the negative-pressure wound dressing is a reliable option, especially for burnt children. Moreover, the negative-pressure wound dressing treatment was not only much cheaper than conventional therapies, but also eliminated hospital stay in patients with small-area deep burn wounds.

Purpose To assess the role of spatial frequency on binocular imbalance in binocular combination in adults with amblyopia. Methods Ten amblyopes (23 ± 4.9 [SD] years old; one deprivation, two mixed, seven anisometropia patients) and 10 age-matched normal adults (23 ± 2.3 years old) participated. The interocular contrast ratio (fellow eye/amblyopic eye, i.e., the balance point [BP]) that resulted in an equal contribution of both eyes in binocular combination was measured using a binocular orientation combination task at 0.5, 1, 2, and 4 cycles per degree (c/d). The extent of binocular imbalance was quantified as the absolute value of the BP on log scale (i.e., |logBP|). Results When the base contrast of the amblyopic eye was set at 100% (Experiment 1), the |logBP| was found to be significantly affected by stimulus spatial frequency (F(1.44, 26.01) = 51.6, P < 0.001, \({\rm{\eta }}_g^2\)= 0.40) and group (F(1, 18) = 66.97, P < 0.001, \({\rm{\eta }}_g^2\) = 0.74), the interaction between spatial frequency and group was also significant (F(1.44, 26.01) = 38.12, P < 0.001, \({\rm{\eta }}_g^2\)= 0.33). Such spatial frequency-dependent binocular imbalance remained present, even when the base contrast of the amblyopic eye was set at equal suprathreshold contrast levels across spatial frequencies (Experiment 2). Conclusions Binocular balance was more disrupted at higher spatial frequencies in binocular combination in amblyopia. This imbalance might not originate solely from the amblyopic eye's deficit in contrast sensitivity but is likely to be related to the difference in contrast sensitivity between the eyes.

Background Previous experimental and occupational health studies have shown the toxic effects of relatively high-level cadmium and lead on lipid metabolism. However, limited studies investigated the relationships between serum lipid levels and exposure to low-level lead and cadmium in adults. Objective To investigate the associations between lead and cadmium levels in blood and dyslipidemia in adults. Methods A retrospective cross-sectional study of 7,457 adults aged 20–79 years who were recruited in the National Health and Nutrition Examination Survey (NHANES, 2005–2016) was conducted. Multivariate linear and logistic regressions were used to examine the associations of blood lead and cadmium levels with serum lipid profiles and risk of dyslipidemia, respectively. Results The weighted geometric means [95% confidence intervals (CIs)] of lead and cadmium in blood were 1.23 (1.21, 1.25) μg/dL and 0.36 (0.35, 0.37) μg/L, respectively. Blood lead was significantly associated with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (Apo B) levels after adjusting for covariates. Compared with the adults in the lowest blood lead quartile (≤0.76 μg/dL), those in the highest lead quartile (>1.90 μg/dL) had higher risks of elevated TC (OR = 1.88, 95% CI: 1.59–2.22), non-HDL-C (OR = 1.59, 95% CI: 1.33–1.91), LDL-C (OR = 1.68, 95% CI: 1.41–1.99) and Apo B (OR = 2.00, 95% CI: 1.46–2.73). However, the single effect of cadmium exposure and the joint effect of lead and cadmium exposures on dyslipidemia were not observed. Conclusion Blood lead well below the current recommended level was positively associated with the risk of dyslipidemia in adults, while the low-level cadmium exposure currently observed in adults did not show any significant associations with lipid levels.