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Although electroacupuncture (EA) stimulation is a widely used therapy for chronic pain and comorbid psychiatric disorders, its long-term effects on chronic neuropathic pain-induced depression and the underlying mechanisms remain elusive. In the present study, we found that EA stimulation was able to restore adult neurogenesis in the ventral dentate gyrus (DG), by both increasing neuronal differentiation and restoring the normal morphology of newborn dendrites, in mice with spared nerve injury surgery. By ablating the Nestin+ neural stem cells (NSCs) via diphtheria toxin fragment A expression, we further proved that neurogenesis in the ventral DG was crucial to the long-term, but not the immediate antidepressant effect of EA, nor was it associated with nociception. Furthermore, we found that the restoration of neurogenesis was dependent on Tet1-mediated epigenetic modification upon EA treatment. Tet1 could bind to the promoter of the Prox1 gene, thus catalyzing its demethylation and facilitating its expression, which finally contributed to the restoration of neurogenesis and amelioration of depression-like behaviors induced by chronic neuropathic pain. Thus, we conclude that EA stimulation restores inhibited Tet1 expression in hippocampal NSCs of mice with chronic neuropathic pain, and increased Tet1 expression ameliorates hypermethylation of Prox1 and restores normal adult neurogenesis in the ventral DG, which contributes to the long-term antidepressant effect of EA.

Our previous study found that activation of adenosine A1 receptor (A

Recent achievements in large-scale pre-trained models like GPT-3 and PanGu-α showed amazing performances in many downstream tasks, which makes AI friendlier toward industrial users. Deep learning has been recognized as the most promising technology for pharmaceuticals, a powerful molecule pre-trained model could save researchers tons of time. In chemistry classes, the students learn two molecule representations, the molecular formula and the structure formula, and learn to translate them from one way to the other. Inspired by this, we developed a novel deep learning architecture using a graph-to-sequence asymmetric conditional variational autoencoders, called PanGu Drug Model, which can appropriately characterize the molecule from both representations and improve the performance of downstream drug discovery tasks. After pretrained with 1.7 billion small molecules, our proposed model achieved the state-of-the-art results in 20 drug discovery tasks, such as molecule property prediction (predict ADMET properties, compound-target interactions, drug-drug interactions and chemical reaction productivity), molecule generation and molecule optimization. A new drug screening library of 100 million drug-like small molecules with 99.68% novelty was generated by PanGu molecule generator, which could efficiently produce novel compounds with similar physiochemical properties to given distribution, this library could be used to supplement existing compound databases. In addition, PanGu molecule optimizer could optimize the chemical structures of starting molecule with improved molecular property of interest. An automatic multi-objective optimization web application implemented by PanGu Drug Model is available at http://www.pangu-drug.com/.

Many grandparents today are physically separated from their families. Given that maintaining close family relationships (with both adult children and grandchildren) is associated with increased physical, mental, and emotional health across generations, it is important to determine how families can maintain close relationships with grandparents when physically separated. Technology offers one potential support: the proliferation of video chat. Recent work suggests that the frequency of video chat and the variety of behaviors engaged in during video calls predicts family closeness and enjoyment of using this communication method, regardless of the physical distance between parties. However, the frequency of grandparent-grandchild video chat varies across families. Here, we explore how demographic, physical (e.g., distance), technological (e.g., number of devices and barriers), and social factors (e.g., children are distracted) predicted: (1) whether or not video chat was used by grandparent-grandchild dyads, and (2) the frequency of video chat in the families using the technology. This work suggests that geographical distance, having met in person, and the number of devices owned were positive predictors of grandparents and grandchildren having ever video chatted. However, the factors associated with the frequency of video chat were different in the parent and grandparent models and included grandparents’ comfort with technology and the type of device used by the parent and child. These findings not only have implications for supporting grandparent-grandchild relationships but also for all family members separated by distance, immigration, incarceration, health emergencies, and displacement.

Cisplatin is recommended as a first-line chemotherapeutic agent against advanced non-small cell lung cancer (NSCLC), but acquired resistance substantially limits its clinical efficacy. Recently, DNA methylation has been identified as an essential contributor to chemoresistance. However, the precise DNA methylation regulatory mechanism of cisplatin resistance remains unclear. Here, we found that nicotinamide nucleotide transhydrogenase (NNT) was silenced by DNA hypermethylation in cisplatin resistance A549 (A549/DDP) cells. Also, the DNA hypermethylation of NNT was positively correlated to poor prognosis in NSCLC patients. Overexpression of NNT in A549/DDP cells could reduce their cisplatin resistance, and also suppressed their tumor malignancy such as cell proliferation and clone formation. However, NNT enhanced sensitivity of A549/DDP cells to cisplatin had little to do with its function in mediating NADPH and ROS level, but was mainly because NNT could inhibit protective autophagy in A549/DDP cells. Further investigation revealed that NNT could decrease NAD

Minimal invasive approach has been increasingly used in total knee arthroplasty (TKA) and more is expected of early rehabilitation in terms of pain release and recovery of knee function. The approach type is one of the major factors that determines the early rehabilitation after TKA. The purpose of this study is to determine whether mini-subvastus approach (MSVA) is superior to the traditional medial parapatellar approach (MPA) in TKA.From 2018 to 2019, a randomized double-blinded prospective study was conducted on 58 patients who underwent simultaneous bilateral TKA. The subjects included eight men and 50 women, with an average age of 65 years. One side was randomized using MSVA and the other side using MPA. Visual analog scale (VAS), operative duration, recovery time to straight leg raising (SLR), range of motion (ROM), HSS score, release rate of lateral retinaculum, satisfaction rate were recorded and compared. Paired-samples T test were used for quantitative data and chi-square test for qualitative data.There was no statistical difference in the ratio of left and right sides, preoperative ROM, VAS, HSS score, muscular strength of lower limbs, KL grade, operative order, and operative duration between the two groups. The average ROM (118.91 ± 8.21 vs. 107.60 ± 7.99, t = 14.320, p = 0.0000) and HSS score (72.03 ± 4.55 vs. 61.22 ± 4.36, t = 13.095, p = 0.0000) on POD 3, VAS in rest and motion on POD 1 and 3, the recovery time to SLR (1.17 ± 0.38 vs. 3.09 ± 0.76, t = 19.902, p = 0.0000), and the satisfaction rate on POD 1 (96.55% vs. 74.14%, χCompared with MPA, MSVA can make ROM of knee and SLR recover earlier, reduce postoperative pain after TKA, improve the early postoperative satisfaction and reduce the lateral release rate. MSVA can be used as a favorable measure in the concept of enhanced recovery after surgery (ERAS).

The relationship between biodiversity and ecosystem functions (BEFs) has attracted great interest. Studies on BEF have so far focused on the average trend of ecosystem function as species diversity increases. A tantalizing but rarely addressed question is why large variations in ecosystem functions are often observed across systems with similar species diversity, likely obscuring observed BEFs. Here we use a multi-trophic food web model in combination with empirical data to examine the relationships between species richness and the variation in ecosystem functions (VEFs) including biomass, metabolism, decomposition, and primary and secondary production. We then probe the mechanisms underlying these relationships, focusing on the role of trophic interactions. While our results reinforce the previously documented positive BEF relationships, we found that ecosystem functions exhibit significant variation within each level of species richness and the magnitude of this variation displays a hump-shaped relationship with species richness. Our analyses demonstrate that VEFs is reduced when consumer diversity increases through elevated nonlinearity in trophic interactions, and/or when the diversity of basal species such as producers and decomposers decreases. This explanation is supported by a 34-year empirical food web time series from the Gulf of Riga ecosystem. Our work suggests that biodiversity loss may not only result in ecosystem function decline, but also reduce the predictability of functions by generating greater function variability among ecosystems. It thus helps to reconcile the debate on the generality of positive BEF relationships and to disentangle the drivers of ecosystem stability. The role of trophic interactions and the variation in their strengths mediated by functional responses in shaping ecosystem function variation warrants further investigations and better incorporation into biodiversity-ecosystem functioning research.

BACKGROUND Warfarin for the prevention of non-valvular atrial fibrillation related thromboembolic stroke in patients on maintenance haemodialysis is controversial. Despite the exclusion of haemodialysis patients in randomised control trials, the American Heart Association/American College of Cardiology has recommended warfarin in high-risk AF patients. AIM We retrospectively examined the utility of warfarin anticoagulation therapy in our prevalent haemodialysis patients over 10 years of follow-up. METHODS Eligible patients were retrospectively identified and stratified to two cohorts based on whether warfarin was prescribed. The outcomes of interest were ischaemic stroke, haemorrhagic stroke and death from any cause. Rate ratio and cox proportional hazard regression model were compare the differences in outcome between the two cohorts. The Kaplan-Meier method was used to analyse survival. RESULTS Three ischaemic strokes and four haemorrhagic strokes occurred in the unexposed group of 166 patients over 484.44 patient-years follow-up. One ischaemic stroke and no cases of haemorrhagic stroke occurred in the exposed warfarin group of 16 patients over 39.32 patient-years of follow-up. 87% of patients in both groups were indigenous. More than 90% of each cohort was had CHA2DS2VaSc score ≥2. 101 deaths occurred in the follow-up period, ninety in the unexposed group and eleven in the warfarin group. A non-statistically significant trend towards increasing mortality was observed in the warfarin group (Hazard ratio =1.63, p=0.13). CONCLUSION This retrospective study of prevalent haemodialysis patients with co-existing history of non-valvular AF failed to demonstrate sufficient evidence for the routine use of warfarin for prophylaxis of thromboembolic stroke. This article is protected by copyright. All rights reserved.

Robot-assisted surgery has been promoted worldwide in recent years. The development of a domestic orthopaedic robot and its clinical application are therefore of great significance. This study aimed to compare the early clinical and radiographic outcomes of domestic robot-assisted total knee arthroplasty (RA-TKA) with conventional manual total knee arthroplasty (CM-TKA).A total of 77 patients who underwent primary single-sided TKA from June to December 2020 were prospectively enrolled; resulting in the inclusion of 72 patients. The patients were randomly divided into the RA-TKA group (37 cases, with TKA being assisted by the Yuanhua Orthopaedic Robotic System) and the CM-TKA group (35 cases, with TKA being performed using conventional tools). Knee function was evaluated by the knee range of motion (ROM), the American Knee Society Score (KSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Postoperative radiographic results were evaluated by full-length weight-bearing X-rays of the lower limb and anteroposterior and lateral X-rays of the knee were obtained preoperatively and at 90 days postoperative. The operative duration, blood loss, postoperative knee function, radiographic outcomes, and incidence of complications were compared by Student's t-test, Mann-Whitney U test, or chi-square test. Serum levels of inflammatory markers before the operation and 1, 3, and 30 days after the operation were recorded and compared between the two groups.The operation was significantly longer in the RA-TKA group than in the CM-TKA group (154.3 vs 115.2 min, p 0.001). There was no significant difference in blood loss (933 vs 863 ml, p = 0.519) between the two groups. The knee ROM, KSS, and WOMAC were significantly improved in both groups 90 days after the operation compared with before the operation (p 0.05), but there were no significant differences between the two groups (p 0.05). The incidence of postoperative deep vein thrombosis was not statistically different between the two groups. In the radiographic findings at 90 days postoperatively we found the frequency of lateral tibial component (LTC) angle outliers was significantly lower in the RA-TKA group (3.0% vs 29.4%, p = 0.003). The neutrophil-to-lymphocyte ratio (NLR) was significantly lower in the RA-TKA group than in the CM-TKA group on day 1 after surgery (9.9 vs 12.7, p = 0.024).RA-TKA requires more time than CM-TKA, which may be related to the learning curve and intraoperative registration. The short-term postoperative knee functional outcomes had no differences between the two groups, and RA-TKA improved the accuracy of tibial component alignment. Further follow-up studies are required to investigate the long-term outcomes.

Chronic pain, such as neuropathic pain, causes anxiety and other negative emotions, which aggravates the pain sensation and increases the risk of chronic pain over time. Dopamine receptor D1 (DRD1) and dopamine receptor D2 (DRD2) in the basolateral amygdala (BLA) have been implicated in mediating anxiety-related behaviors, but their potential roles in the BLA in neuropathic pain-induced anxiety have not been examined. Electroacupuncture (EA) is commonly used to treat chronic pain and emotional disorders, but it is still unclear whether EA plays a role in analgesia and anxiety relief through DRD1 and DRD2 in the BLA. Here, we used western blotting to examine the expression of DRD1 and DRD2 and pharmacological regulation combined with behavioral testing to detect anxiety-like behaviors. We observed that injection of the DRD1 antagonist SCH23390 or the DRD2 agonist quinpirole into the BLA contributed to anxiety-like behaviors in naive mice. EA also activated DRD1 or inhibited DRD2 in the BLA to alleviate anxiety-like behaviors. To further demonstrate the role of DRD1 and DRD2 in the BLA in spared nerve injury (SNI) model-induced anxiety-like behaviors, we injected the DRD1 agonist SKF38393 or the DRD2 antagonist sulpiride into the BLA. We found that both activation of DRD1 and inhibition of DRD2 could alleviate SNI-induced anxiety-like behaviors, and EA had a similar effect of alleviating anxiety. Additionally, neither DRD1 nor DRD2 in the BLA affected SNI-induced mechanical allodynia, but EA did. Overall, our work provides new insights into the mechanisms of neuropathic pain-induced anxiety and a possible explanation for the effect of EA treatment on anxiety caused by chronic pain.

Objectives To investigate the value of quantitative parameters of Dual-layer spectral detector CT (SDCT) in the differentiation grade, T stage, and lymph node metastasis stage of colorectal adenocarcinoma (CRAC).Methods 86 eligible CRAC patients were included in this study. The conventional CT values, 40 keV values, 100 keV values, effective atomic number (Zeff) values, iodine concentration (IC) values, normalized iodine concentration (NIC) and spectral curve slope (λ) during the arterial phase (AP) and venous phase (VP) of CRAC were compared according to the differentiation grade, T stage, and lymph node metastasis stage.Results The measured values of the spectral quantitative parameters of the CRAC were consistent within the observer (ICC range 0.791–0.979). The 100kev-AP, RT-VP, 40keV-VP, 100keV-VP, Zeff-VP, IC-VP, λ-VP had significant differences among different grades of CRAC differentiation (P 0.05).Conclusion The quantitative parameters of SDCT had good diagnostic efficacy in differentiating differentiation grades of CRAC, however did not show the value for identifying T stage and lymph node metastasis stage.

Background The learning curve of single-port thoracoscopic lobectomy (SPTL) in lung cancer has been widely studied. However, the efficiency of different experience levels of thoracic surgeons in mastering the learning curve is unknown. Hence, we discuss this issue in depth by using several perioperative parameters and oncological outcomes. Methods A total of 120 consecutive cases of SPTL performed by a senior (STS group) and junior (JTS group) thoracic surgeons were retrospectively analyzed. Operation time, estimated blood loss, and duration of postoperative hospital stay were recorded for cumulative summation (CUSUM) learning curve analysis, while the 5-year survival rate was used for oncological evaluation. Results The CUSUM learning curve of the STS group was y = 0.000106x3 − 0.019x2 + 0.852x − 0.036, with a high R-value of 0.9517. When the number of cases exceeded 33, the slope changed from positive to negative. The CUSUM learning curve of the JTS group was y = 0.000266x3 − 0.04x2 + 1.429 × –0.335, with a high R-value of 0.9644. When the number of cases exceeded 25, the slope changed from positive to negative. The learning curve was divided into two phases (phases 1 and 2). The slope of the JTS group in phase 1 was greater than that of the STS group in phase 1 (p p > 0.05). In addition, the 5-year survival rate was not significantly different between the two groups (p = 0.72). Conclusion This is the first study to analyze the learning curve of thoracic surgeons with different experience levels in mastering SPTL. Moreover, it is also the first study to include multiple perioperative parameters and overall survival to study how quickly surgeons master the SPTL technique. The junior thoracic surgeon was found to have a shorter learning curve for SPTL.

The effects of an external electric field on the structure and stability of the nitrogen hydrate confined in a singlewalled carbon nanotube (CNT) were studied by using molecular dynamics (MD) simulations. It was found that the structure of the nitrogen hydrate, the occupancy and distribution of the nitrogen molecules inside the nanotube depend sensitively on the direction of the external electric field. A parallel electric field can destabilize the nitrogen hydrate and cause the release of nitrogen molecules from the ice nanotube of the hydrate. While a vertical electric field can redistribute the nitrogen molecules from the core to the shell of the hydrate. The occupancy of the nitrogen molecules of the hydrate follows a sigmoid-like function as the direction of the electric field changes. Our findings may aid in the development of methods to control gas release and encapsulation by using electric fields.

Periprosthetic joint infection (PJI) is the most devastating complication following total joint arthroplasty (TJA) and is posing a global healthcare challenge as the demand for TJA mounts. Two-stage exchange arthroplasty with the placement of antibiotic-loaded spacers has been shown to be efficacious against chronic PJI. This study aimed to review the key concepts, types, and outcome evaluations of articulating spacers in the two-stage exchange for PJI. Previous studies indicated that articulating spacers have been widely used due to better functional improvement and a comparable infection control rate relative to static spacers. Several types of articulating spacers are reportedly available, including hand-made spacers, spacers fashioned from molds, commercially preformed spacers, spacers with additional metal or polyethylene elements, new or autoclaved prosthesis, custom-made articulating spacers, and 3D printing-assisted spacers. However, limited evidence suggested no significant difference in clinical outcomes among the different subtypes of articulating spacers. Surgeons should be familiar with different treatment strategies when using various spacers to know which is the most appropriate.

RCF1 is a highly conserved DEAD-box helicase found in yeast, plants and mammals. Studies about the functions of RCF1 in plants are limited. Here we uncovered the functions of RCF1 inArabidopsis thalianaas a player in pri-miRNA processing and splicing, as well as in pre-mRNA splicing. A mutant with miRNA biogenesis defects was isolated and the defect was traced to a recessive point mutation inRCF1(rcf1-4). We show that RCF1 promotes D-body formation and facilitates the interaction between pri-miRNAs and HYL1. Finally, we show that intron-containing pri-miRNAs and pre-mRNAs exhibit a global splicing defect inrcf1-4. Together, this work uncovers roles for RCF1 in miRNA biogenesis and RNA splicing inArabidopsis.One-sentence summaryRCF1 promotes not only the processing of pri-miRNAs, but also the splicing of intron-containing pri-miRNAs, therefore promotes miRNA biogenesis.

HER2/EGFR signaling alters the responsiveness of breast cancer cells to TGF-β.

HER2/EGFR signaling induces Smad3 S208 phosphorylation through AKT

Table S1 lists shRNA sequences from Sigma. Table S2 lists antibodies used in this study. Table S3 lists chemical inhibitors used in this study. Table S4 lists cell lines used in this study. Table S5 lists RT-qPCR primers and ChIP-qPCR primers used in this study

S208 phosphorylation is important for Smad3 nuclear accumulation

HER2/EGFR signaling enhances Smad3 nuclear accumulation

HER2/EGFR signaling stimulates Smad3 S208 phosphorylation

Knockdown of Smad3 and Smad2 attenuates TGF-β-induced anti-proliferation of MDA-MB-231 cells in the presence of Lapatinib; Smad3(S208) phosphorylation is positively correlated with HER2 activation and AKT activity in human breast cancer tissues.

TGFβ signaling inhibits cell proliferation to block cancer initiation, yet it also enhances metastasis to promote malignancy during breast cancer development. The mechanisms underlying these differential effects are still unclear. Here, we report that HER2/EGFR signaling switches TGFβ function in breast cancer cells from antiproliferation to cancer promotion. Inhibition of HER2/EGFR activity attenuated TGFβ–induced epithelial–mesenchymal transition and migration but enhanced the antiproliferative activity of TGFβ. Activation of HER2/EGFR induced phosphorylation of Smad3 at Ser208 of the linker region through AKT, which promoted the nuclear accumulation of Smad3 and subsequent expression of the genes related to EMT and cell migration. In contrast, HER2/EGFR signaling had no effects on the nuclear localization of Smad2. Knockdown of Smad3, but not Smad2, blocked TGFβ–induced breast cancer cell migration. We observed a positive correlation between the nuclear localization of Smad3 and HER2 activation in advanced human breast cancers. Our results demonstrate a key role for HER2/EGFR in differential regulation of Smad3 activity to shift TGFβ function from antitumorigenic to protumorigenic during breast cancer development.Significance: TGFβ signaling can shift from inhibiting to promoting breast cancer development via HER2/EGFR AKT-mediated phosphorylation of Smad3 at S208, enhancing its nuclear accumulation and upregulation of EMT-related genes.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/21/6073/F1.large.jpg. Cancer Res; 78(21); 6073–85. ©2018 AACR.

Background Low back pain (LBP) from hip and spinal disorders has been one of the main reasons for visiting physicians in patients with developmental dysplasia of the hip (DDH). It is essential to identify the LBP improvement among all grades of DDH patients treated with total hip arthroplasty (THA) at 5-year follow-up. Methods The study included 407 hips of 306 patients (38 males, 268 females) who underwent THA between July 2007 and December 2016. There were 65 hips in Crowe I, 61 hips in Crowe II, 69 hips in Crowe III, and 212 hips in Crowe IV. One hundred and fourteen hips received subtrochanteric shortening. Patients included 101 bilateral THA (BTHA) and 205 unilateral THA (UTHA). The evaluation was performed through Back Pain Function Scale (BPFS), Harris hip score, Visual Analogue Scale (VAS), operative data and radiographic examinations. Results The BPFS in patients of unilateral Crowe III and IV relieved significantly more (p 0.05). However, the BPFS in patients with bilateral symmetry DDH hips relieved significantly less than other groups of DDH hips (p 0.05). Harris in hips of Crowe II improved significantly more (p 0.05). The VAS in hips of Crowe II and III improved significantly more (p 0.05). The unilateral THA surgical time, blood loss, blood transfusion, and osteotomy number and length in Crowe IV were significantly more (p 0.05). Conclusion THA is reliable to relieve LBP in DDH patients of unilateral Crowe III and IV; however, in patients with unilateral Crowe I, Crowe II, and bilateral DDH hips, the LBP improvements were limited. This should assist shared decision-making between orthopedic surgeons and patients. Level of evidence Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Cardiac aging is evident by a reduction in function which subsequently contributes to heart failure. The metabolic microenvironment has been identified as a hallmark of malignancy, but recent studies have shed light on its role in cardiovascular diseases (CVDs). Various metabolic pathways in cardiomyocytes and noncardiomyocytes determine cellular senescence in the aging heart. Metabolic alteration is a common process throughout cardiac degeneration. Importantly, the involvement of cellular senescence in cardiac injuries, including heart failure and myocardial ischemia and infarction, has been reported. However, metabolic complexity among human aging hearts hinders the development of strategies that targets metabolic susceptibility. Advances over the past decade have linked cellular senescence and function with their metabolic reprogramming pathway in cardiac aging, including autophagy, oxidative stress, epigenetic modifications, chronic inflammation, and myocyte systolic phenotype regulation. In addition, metabolic status is involved in crucial aspects of myocardial biology, from fibrosis to hypertrophy and chronic inflammation. However, further elucidation of the metabolism involvement in cardiac degeneration is still needed. Thus, deciphering the mechanisms underlying how metabolic reprogramming impacts cardiac aging is thought to contribute to the novel interventions to protect or even restore cardiac function in aging hearts. Here, we summarize emerging concepts about metabolic landscapes of cardiac aging, with specific focuses on why metabolic profile alters during cardiac degeneration and how we could utilize the current knowledge to improve the management of cardiac aging.

Background The risk of death in sepsis patients with acute respiratory distress syndrome (ARDS) was as high as 20–50%. Few studies focused on the risk identification of ARDS among sepsis patients. This study aimed to develop and validate a nomogram to predict the ARDS risk in sepsis patients based on the Medical Information Mart for Intensive Care IV database. Methods A total of 16,523 sepsis patients were included and randomly divided into the training and testing sets with a ratio of 7:3 in this retrospective cohort study. The outcomes were defined as the occurrence of ARDS for ICU patients with sepsis. Univariate and multivariate logistic regression analyses were used in the training set to identify the factors that were associated with ARDS risk, which were adopted to establish the nomogram. The receiver operating characteristic and calibration curves were used to assess the predictive performance of nomogram. Results Totally 2422 (20.66%) sepsis patients occurred ARDS, with the median follow-up time of 8.47 (5.20, 16.20) days. The results found that body mass index, respiratory rate, urine output, partial pressure of carbon dioxide, blood urea nitrogen, vasopressin, continuous renal replacement therapy, ventilation status, chronic pulmonary disease, malignant cancer, liver disease, septic shock and pancreatitis might be predictors. The area under the curve of developed model were 0.811 (95% CI 0.802–0.820) in the training set and 0.812 (95% CI 0.798–0.826) in the testing set. The calibration curve showed a good concordance between the predicted and observed ARDS among sepsis patients. Conclusion We developed a model incorporating thirteen clinical features to predict the ARDS risk in patients with sepsis. The model showed a good predictive ability by internal validation.

This paper considers a model for oncolytic virotherapy given by the doubly haptotactic cross-diffusion system \[ \left\{\begin{array}{@{}ll} u_t=D_u\Delta u-\xi_u\nabla\cdot(u\nabla v)+\mu_u u(1-u)-\rho uz,\\ v_t={-} (\alpha_u u+\alpha_w w)v,\\ w_t=D_w\Delta w-\xi_w\nabla\cdot(w\nabla v)- w+\rho uz,\\ z_t=D_z\Delta z-\delta_z z- \rho uz+\beta w, \end{array}\right. \]with positive parameters $D_u,D_w,D_z,\xi _u,\xi _w,\delta _z,\rho$, $\alpha _u,\alpha _w,\mu _u,\beta$. When posed under no-flux boundary conditions in a smoothly bounded domain $\Omega \subset {\mathbb {R}}^{2}$, and along with initial conditions involving suitably regular data, the global existence of classical solution to this system was asserted in Tao and Winkler (2020, J. Differ. Equ. 268, 4973–4997). Based on the suitable quasi-Lyapunov functional, it is shown that when the virus replication rate $\beta , the global classical solution $(u,v,w,z)$ is uniformly bounded and exponentially stabilizes to the constant equilibrium $(1, 0, 0, 0)$ in the topology $(L^{\infty }(\Omega ))^{4}$ as $t\rightarrow \infty$.

To report the long-term outcomes of total hip arthroplasty (THA) with fourth-generation ceramic-on-ceramic (CoC) bearing in patients with ankylosing spondylitis (AS).We retrospectively identified 180 primary THAs performed in 110 patients with AS, including 100 (90.9%) men and 10 women (9.1%), from 2009 to 2011.The mean age of the patients at surgery was 33 years (range, 16 to 65 years). Cementless prostheses with fourth-generation CoC bearings were used in all patients. Survivorship of the implants and postoperative complications were calculated. Functional improvement was assessed by the hip flexion-extension range of motion (ROM) and Harris hip score (HHS). A special noise assessment questionnaire was performed at the last follow-up. The cumulative incidence of noise was calculated by the Kaplan-Meier method with 95% confidence intervals (CIs). Clinical characteristics and functional outcomes were compared in the hips with noise to those without noise.The mean follow-up was 11 years (range, 10 to 12 years), and survivorship of the implants was 99.4% at the most recent follow-up. The complications included dislocation (one hip, 0.6%), periprosthetic joint infection (one hip, 0.6%), mild to moderate pain (five hips, 2.8%), heterotopic ossification (12 hips, 6.7%), and noise (52 hips, 28.9%). The flexion-extension ROM improved significantly with a median from 10° (range, 0 ~ 130°) to 100° (30 ~ 130°) after THA (p 0.001), and the HHS increased significantly from 41 ± 20 to 90 ± 8 (p 0.001). The cumulative incidence of noise at 0.5, 5, and 10 years was 6.1% (95% CI, 2.6 ~ 9.6), 16.7% (95% CI, 11.2 ~ 22.1), and 28.9% (95% CI, 22.2 ~ 35.5), respectively, and that of squeaking at 0.5, 5, and 10 years was 4.4% (95% CI, 1.4 ~ 7.4), 13.3% (95% CI, 8.4 ~ 18.3), and 23.9% (95% CI, 17.6 ~ 30.1), respectively. None of the patients with noise generation in the hip reported it affecting daily activities or causing dissatisfaction. No differences in age, sex, BMI, disease duration, bilateral THA, the frequency of bony ankylosis, the proportion of using a 36-mm-diameter femoral head, pre/postoperative flexion-extension ROM, or pre/postoperative HHS were found between hips with noise and those without noise (p 0.05).THAs with fourth-generation CoC bearings exhibit excellent long-term survival and clinical outcomes in patients with AS, with a very low dislocation rate. The incidence of noise associated with CoC bearings in THA performed in patients increases over time, but it does not affect postoperative hip function or daily activities.

Air pollution poses a major threat to global public health. Although there have been a few investigations into the relationships between organic pollutants and adverse outcomes, the responsible components and molecular mechanisms may be ignored. In this study, a suspect screening method combining comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF MS) with the Toxicity Forecaster (ToxCast) database was applied to analyze complex hydrophobic compounds in ambient air and prospectively figure out toxicologically significant compounds. Seventy-six ToxCast compounds were screened, including seven pollutants receiving less attention and five chemicals never published in the air previously. Given the concentrations, bioactivities, as well as absorption, distribution, metabolism, and excretion properties in vivo, 29 contaminants were assigned high priority since they had active biological effects in the vascular, lung, liver, kidney, prostate, and bone tissues. Phenotypic linkages of key pollutants to potential mechanistic pathways were explored by systems toxicology. A total of 267 chemical-effect pathways involving 29 toxicants and 31 molecular targets were mapped in bipartite network, in which 12 key pathogenic pathways were clarified, which not only provided evidence supporting the previous hypothesis but also provided new insights into the molecular targets. The results would facilitate the development of pollutant priority control, population intervention, and clinical therapeutic strategies so as to substantially reduce human health hazards induced by urban air.