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Background Since December 2019, coronavirus disease 2019 (COVID‐19) has emerged as an international pandemic. COVID‐19 patients with myocardial injury might need special attention. However, an understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury to COVID‐19 patients. Methods This retrospective, single‐center study finally included 304 hospitalized COVID‐19 cases confirmed by real‐time reverse‐transcriptase polymerase chain reaction from January 11 to March 25, 2020. Myocardial injury was determined by serum high‐sensitivity troponin I (Hs‐TnI). The primary endpoint was COVID‐19‐associated mortality. Results Of 304 COVID‐19 patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury, 27 patients without myocardial injury on admission). COVID‐19 patients with myocardial injury had more comorbidities (hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease); lower lymphocyte counts, higher C‐reactive protein (CRP; median, 84.9 vs. 28.5 mg/L; p, COVID patients with myocardial injury on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury (hazard ratio = 4.55; p

Lei Gao,1,2,&ast; Jian-Feng Zhang,3,&ast; John P Williams,4 Yi-Ning Yan,1 Xi-Lai Xiao,1 Wan-Rui Shi,5 Xiao-Yan Qian,1 Jian-Xiong An1– 3,6 1Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2School of Anesthesiology, Weifang Medical University, Weifang, Shangdong, People’s Republic of China; 3Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 5Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 6School of Medical Science & Engineering, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Xiong AnDepartment of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University, Beiyuan Road 3#, Beijing, 100012, People’s Republic of ChinaTel +86 13801281750Fax +86 59520233Email anjianxiong@yeah.netPurpose: It is unclear whether neuropathological structural changes in the peripheral nervous system and central nervous system can occur in the spared nerve injury model. In this study, we investigated the pathological changes in the nervous system in a model of neuropathic pain as well as the effects of electroacupuncture (EA) and pregabalin (PGB) administration as regards pain relief and tissue repair.Patients and Methods: Forty adult male SD rats were equally and randomly divided into 4 groups: spared nerve injury group (SNI, n = 10), SNI with electroacupuncture group (EA, n = 10), SNI with pregabalin group (PGB, n =10) and sham-operated group (Sham, n=10). EA and PGB were given from postoperative day (POD) 14 to 36. EA (2 Hz and 100 Hz alternating frequencies, intensities ranging from 1– 1.5– 2 mA) was applied to the left “zusanli” (ST36) and “Yanglingquan” (GB34) acupoints for 30 minutes. The mechanical withdrawal thresholds (MWTs) were tested with von Frey filaments. Moreover, the organizational and structural alterations of the bilateral prefrontal cortex, hippocampus, sciatic nerves and the thoracic, lumbar spinal cords and dorsal root ganglions (DRGs) were examined via light and electron microscopy.Results: MWTs of left hind paw demonstrated a remarkable decrease in the SNI model (P < 0.05). In the SNI model, ultrastructural changes including demyelination and damaged neurons were observed at all levels of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, EA improved MWTs and restored the normal structure of neurons. However, the effect was not found in the PGB treatment group.Conclusion: Chronic pain can induce extensive damage to the central and peripheral nervous systems. Meanwhile, EA and PGB can both alleviate chronic pain syndromes in rats, but EA also restores the normal cellular structures, while PGB is associated with no improvement.Keywords: neuropathic pain, structural changes, electroacupuncture, pregabalin

BACKGROUND Due to improvements in living standards, people are now paying more attention to their health. In China, more patients choose to go to large or well-known hospitals, which leads to constant crowding of outpatient clinics in these hospitals. AIM To establish precision valuation reservation registration aimed at shortening waiting time, improving patient experience and promoting the satisfaction of outpatients and medical staff. METHODS On the basis of the implementation of a conventional appointment system, more reasonable time intervals were set for different doctors by evaluating the actual capacity of each doctor to receive patients, and appointment times were made more accurate through intervention. The change in consultation waiting time of patients was then compared. Correlations between the consultation waiting time of patients and the satisfaction of patients or satisfaction of medical staff were analyzed. RESULTS After precision valuation reservation registration, the average consultation waiting time of patients reduced from 18.47 min to 10.11 min (t = 8.90, P < 0.001). The satisfaction score of patients increased from 91.33 to 96.27 (t = -8.62, P < 0.001), and the satisfaction score of medical staff increased from 90.51 to 96.04 (t = -10.50, P < 0.001). The consultation waiting time of patients was negatively correlated with their satisfaction scores (γ = -0.89, P < 0.001). The consultation waiting time of patients was also negatively correlated with medical staff satisfaction scores (γ = -0.96, P < 0.001). CONCLUSION Precision valuation reservation registration significantly shortened outpatient waiting times and improve the satisfaction of not only patients but also medical staff. This approach played an important role in improving outpatient services, provided a model that is supported by relevant evidence and could continuously improve the quality of management. Precision valuation reservation registration is worth promoting and applying in the clinic.

Aims Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. Method and results MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and type 2 innate lymphoid cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. Conclusion IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Translational perspective Accumulating evidence suggests that modulation of innate and adaptive immune responses is a promising therapeutic strategy for myocardial infarction. In this study, we demonstrate that IL-5 exerts cardioprotective effects on infarcted myocardium by promoting eosinophil accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Hence, regulation of cardiac IL-5 level or eosinophil count may become a therapeutic approach for post-myocardial infarction cardiac repair in humans.

Background Tuberculosis (TB) is a widespread infectious disease, with an incidence that is increasing worldwide. Cutaneous TB (CTB) occurs rarely, accounting for less than 1% of all TB cases. Due to the clinical presentation and diagnostic difficulties, CTB is often clinically neglected and misdiagnosed. Case summary A 32-year-old man underwent several debridement surgeries and skin flap transplantation after trauma. The wound remained unhealed, accompanied by sinus formation. According to empirical judgment, T-cell spot of TB test, and bacterial culture of pyogenic fluids, he was diagnosed with CTB due to infection with exogenous Mycobacterium tuberculosis. A comprehensive anti-TB regimen that included isoniazid, rifampicin, ethambutol, and pyrazinamide was applied. The sinus was filled with a hydrophilic fiber-containing silver dressing, and wound-protecting sponges were applied to part of the wound. The wound healed after 40 d. No ulceration was found within 2 mo after discharge; further follow-up will be conducted. Conclusion A non-healing wound may be caused by TB infection. Comprehensive treatment of CTB is effective.

Background: Numerous therapies have been developed for the treatment of chronic pelvic pain (CPP). Oxygen-ozone therapy is a new method for the treatment of CPP. Objectives: This article evaluated the feasibility of ultrasound-guided peritoneal perfusion with ozone in patients with CPP. Study Design: This is a bicenter retrospective study. Setting: The study was conducted at 2 pain centers of a university hospital. Methods: The medical records of patients with CPP (n = 60) from March 2016 until October 2018 were collected and reviewed. Group A contained 19 patients who were treated with a 1500 mcg dose of ozonated water (10 mcg/mL concentration and 150 mL volume), group B contained 23 patients using the same dose of ozonated water but a 15 mcg/mL concentration and 100 mL volume. Group C included 18 patients using a similar ozone dose but delivered in an oxygen-ozone mixture (15 mcg/mL concentration and 100 mL volume oxygen-ozone mixture). Visual Analog Scale (VAS) scores for pain of the 3 groups were compared at pretreatment, posttreatment, 1, 3, and 6 months posttreatment. The injection pain was evaluated using a 4-point verbal rating scale. Quality of life (QoL), anxiety, and depression were assessed at pretreatment and at 6 months posttreatment. Results: The VAS scores of the 3 groups decreased over time following treatment. Group A showed much higher pain scores compared with groups B and C at 1, 3, and 6 months posttreatment. However, the injection pain for groups B and C was higher than group A, but there was no difference seen between group B and C. At 6 months posttreatment, the QoL for all patients improved compared with pretreatment, whereas the anxiety and depression did not demonstrate differences. Limitations: The main limitations of this study are the retrospective study design, limited case number, and short follow-up period. Conclusions: Ultrasound-guided peritoneal perfusion with ozone is a feasible therapy for patients with CPP. Key words: Chronic pelvic pain, ozone, peritoneal perfusion

Objective Given that the presence of insurance may affect the risk of suicide mortality in cancer patients, we aimed to examine the association in a population-based study using the Surveillance, Epidemiologic, and End Results (SEER) database. Study design A retrospective analysis of data from the SEER database. Methods We conducted a retrospective study using the SEER database. Hazard ratios (HRs), adjusted HRs (aHRs), and 95% confidence intervals (95% CIs) of suicide death were calculated using Cox proportional hazard models to evaluate the risk of suicide mortality among the cohorts. Results Multivariable analysis revealed that cancer patients without insurance had an increased risk of suicide death compared with patients with private insurance (aHR, 1.37; 95% CI, 1.01–1.72), whereas no significant result was observed in patients with any Medicaid (aHR, 1.10; 95% CI, 0.93–1.30; P = 0.27). In addition, the stratified analysis indicated that the risk of suicide death in patients in the uninsured and Medicaid groups presented with localized stage of disease (aHR, 1.32; 95% CI, 1.02, 1.69), White (aHR, 1.34; 95% CI, 1.05, 1.71), and American Indian/Alaska Native and Asian/Pacific Islander (aHR, 1.89; 95% CI, 1.08, 3.30) were greater than insured patients. Conclusion Overall, our results indicated that insurance status was a statistically significant predictor of suicide death in patients with cancer. Healthcare providers should identify those patients at high risk of suicide and provide appropriate mental health and psychosocial oncology services in time.

Background Spinal cord injury (SCI) is the most serious complication of spinal injury, often leading to severe dysfunction of the limbs below the injured segment. Conventional therapy approaches are becoming less and less effective, and gene therapy is a new research direction by now. Methods The Sprague-Dawley rats were haphazardly assigned to two groups, namely sham group and SCI model group, and lncRNA H19 and miR-370-3p levels were investigated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Correlation between lncRNA H19 and miR-370-3p was ascertained by luciferase report assay and RT-qPCR. After transfection with si-H19, miR-370-3p inhibitor, negative controls (NC), or both, primary spinal neurons were subjected to the simulation of lipopolysaccharide (LPS) for inducing in vitro model of SCI. Cell viability, apoptotic rate, caspase-3 activity, Bax and Bcl-2 protein, ROS generation, TNF-α, IL-1β, and IL-6 protein, as well as IκBα and p65 phosphorylation ratio were evaluated adopting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), apoptosis, caspase-3 activity, ROS generation, and western blot assays, thereby searching for the specific action mechanism on LPS-induced spinal never injury. Results SCI resulted in lncRNA H19 higher expression and miR-370-3p lower expression. LPS simulation raised a series of cellular biological changes, such as decreased viability, promoted apoptosis, generated ROS, and released inflammatory factors. lncRNA H19 inhibition reversed above LPS-induced changes. Besides, as the downstream target of lncRNA H19, miR-370-3p was oppositely regulated by lncRNA H19. The above biological changes induced by lncRNA H19 inhibition were reversed by miR-370-3p upregulation. Moreover, lncRNA H19 inhibition could block NF-κB pathway through miR-370-3p upregulation. Conclusion Inhibition of lncRNA H19/miR-370-3p mitigated spinal neuron apoptosis in an in vitro model of SCI. This provided the possibility for clinical use of gene therapy.

Pseudomonas aeruginosa (PA) is a common gram-negative bacterium. Imipenem (IMP) is considered to be the most effective clinical drug for the treatment of PA infection. IMP-resistant ceftazidime-susceptible PA is relatively rare in clinical practice; so far, there have been no clinical reports regarding the treatment of IMP-resistant PA with piperacillin/tazobactam alone. This paper will report the case of a severe pneumonia patient with IMP-resistant ceftazidime-susceptible PA infection that was successfully treated with piperacillin/tazobactam monotherapy after initial therapy with biapenem (BIP) according to the drug sensitivity test. The patient was a 75-year-old female, her main symptom was drowsiness. She was admitted to hospital due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and pulmonary encephalopathy. After admission, endotracheal intubation was performed immediately, and the lavage fluid was sent to the laboratory for sputum culturing for several times. BIP was selected for the initial anti-infection regimen, and other symptomatic treatments were performed at the same time. On the day 8, the sputum culture drug sensitivity test results showed PA (sensitive to: piperacillin/tazobactam sodium, ceftazidime, aminoglycoside, and fluoroquinolones; resistant to IMP; and intermediate sensitivity to: cefoperazone-sulbactam and meropenem), so we adjusted the anti-infection regimen as piperacillin/tazobactam sodium. After that, the infection index of the patient declined steadily, and the patient was discharged from hospital after continuous treatment with piperacillin tazobactam until the 24th day. For severe pneumonia patients with IMP-resistant ceftazidime-susceptible PA infection, piperacillin/tazobactam is still an option specially when the MIC of piperacillin/tazobactam is very low.

Background: Growing evidence indicated the higher risk of suicide in cancer survivors compared with general population. Our aim is to systematically quantify the extent of suicide death and identify risk factors associated with the incidence of suicide in cancer patients. Methods: We conducted a meta-analysis of relevant studies published in English or Chinese before May 20, 2020. Suicide rate and the number of suicide death were extracted. Our main outcome was suicide rate per 100,000 person-years with 95% CIs using random-effects model. Results: The pooled incidence of suicide death was 39.72 per 100,000 person-years (95%CI, 33.91–46.52, I 2= 99.6%, P Limitations: Included studies came from high-income countries and our results might not represent the suicide rate among cancer patients in low- and middle-income countries. Conclusions: The incidence of suicide among cancer patients was high despite the declined trend recent years, which emphasized psychological health aspects of interventions and perfecting suicide prevention programs.

The outbreak of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a major health crisis and a worldwide pandemic. COVID‐19 is characterized by high infectivity, long incubation period, diverse clinical presentations, and strong transmission intensity. COVID‐19 can cause myocardial injury as well as other cardiovascular complications, particularly in senior patients with pre‐existing medical conditions. The current review summarizes the epidemiological characteristics, potential mechanisms, clinical manifestations, and recent progress in the management of COVID‐19 cardiovascular complications.

Some patients with diabetic foot ulcers (DFUs) may suffer from depression, but the latest information regarding the incidence of depression in patients with DFUs is limited. This review aimed to provide up-to-date information concerning the incidence of depression in patients with DFUs. We searched the literature in PubMed and Web of Science databases, limited to English publications. 11 eligible studies with a total of 2117 participants were included in this review. A random-effects model was applied due to high heterogeneity. The incidence of depression in patients with DFUs ranged from 26% (95% confidence interval [CI] = 19% to 33%) to 85% (95% CI = 78% to 92%), and was 47% (95% CI = 36% to 58%) after systematically summarizing. Subgroup analyses suggested that the incidence of depression were 49% (95%CI = 35% to 63%) in Europe, 37% (95% CI = 23% to 51%) in Asia, 62% (95% CI = 48% to 76%) in North America. Additionally, the incidence of depression were 40% (95% CI = 29% to 50%) in prospective studies, 55% (95% CI = 28% to 82%) in retrospective studies, 40% (95% CI = 29% to 50%) in cross-sectional studies. Furthermore, the incidence of depression were 43% (95% CI = 25% to 60%), 49% (95% CI = 35% to 63%), 68% (95% CI = 35% to 102%), 32% (95% CI = 26% to 38%), and 28% (95% CI = 18% to 38%) in patients with DFUs assessed by the Hospital Anxiety and Depression Scale, EuroQol 5-Dimension Questionnaire, Geriatric Depression Scale, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the Center for Epidemiologic Studies Depression Scale, respectively. The estimates were robust in the sensitivity analysis. According to the meta-regression analyses, diabetes mellitus duration ( t = 0.93, P = .422), publication years ( t = −0.72, P = .488), and age of subjects ( t = 0.01, P = .989) were not the sources of high heterogeneity. Our meta-analysis showed nearly half of patients with DFUs had depression problems.

The efficient separation of hexane isomers from the light naphtha fraction is a significant challenge in the petrochemical industry. 5A zeolite adsorbent is used commercially to sieve alkane isomers. In this study, 5A zeolites were synthesized using a low-cost natural clay mineral precursor, i.e. palygorskite (PAL), with the addition of crystallization directing agent (CDA). By varying the mass ratio of CDA/deionized water, 5A zeolites were obtained as CDA-5%, CDA-7.5%, and CDA-10%. All products were submicron particles with an average particle size of 400–800 nm. A sieving test of CDA-induced 5A zeolites was carried out on hexane adsorbates including n-hexane (nHEX), 2-methylpentane (2MP), and 3-methylpentane (3MP). According to vapor-phase batch adsorption experiments, a significant equilibrium amount (0.149 g/g) of nHEX and only 0.0321 g/g 2MP and 0.0416 g/g 3MP were adsorbed on the 5A zeolite product with CDA-5%. The dynamic adsorption performance of 5A zeolite (CDA-5%) was evaluated by breakthrough curves of binary mixtures of nHEX/2MP and nHEX/3MP. Palygorskite 5A (PAL 5A) zeolite achieved maximum dynamic adsorption capacities of nHEX (0.16 g/g in both cases) at 200°C and 1.2 MPa total pressure. This work provided an economic alternative for the synthesis of 5A zeolites using natural clay minerals instead of chemical raw materials.

Gastric cancer (GC) is one of the most common malignancies worldwide. The prognosis of GC is unsatisfied owning to widespread metastasis. P21-activated kinase 1 (PAK1), a member of serine/threonine kinases, is associated with the progression of multiple types of human cancers. Here, we demonstrated that CDK4/6 inhibitor reduced GC cell viability and decreased PAK1 expression. Consistently, PAK1 ablation increased GC cell sensitivity exposed to CDK4/6 inhibitor and promoted DNA damage. We also revealed PAK1 depletion notably affected PDK1-AKT pathway, and PDK1 overexpression totally abrogated the effect of PAK1 deletion on DNA damage in GC cells. Additionally, PDK1 overexpression also rescued the increased GC cell sensitivity towards CDK4/6 inhibitor and the cell cycle arrest caused by PAK1 depletion. Our findings, therefore, suggested that PAK1 silencing increased sensitivity to CDK4/6 inhibition in gastric cancer cells via PDK1-AKT pathway. We, therefore, thought PAK1 as a promising therapeutic target for the treatment of CDK4/6 inhibitor-resistant gastric cancer.

MicroRNAs are dysregulated in traumatic brain injury and are involved in neuronal cell behaviors. Previous studies identified miR-31 as a spinal cord injury-related microRNA, while its role in traumatic brain injury remains indistinct. Herein, we explored the participation of miR-31 in traumatic brain injury. Traumatic brain injury model was established after traumatic neuron injury. Neurocytes were transfected with miR-31 mimic or inhibitor. Cell counting kit-8, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and western blot were applied to examine cell viability, lactate dehydrogenase releasing, apoptosis, and apoptosis-related protein. The binding between miR-31 and hypoxia-inducible factor-1A was verified by luciferase assay. Quantitative reverse transcription-PCR was used to detect the regulation of traumatic neuron injury or hypoxia-inducible factor-1A overexpression on vascular endothelial growth factor A level. The effects of hypoxia-inducible factor-1A or vascular endothelial growth factor A on neuronal cell injury were examined. Additionally, phosphatidylinositol 3kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was also examined using western blot. Downregulation of miR-31 promoted traumatic neuron injury-induced neuronal cell injury, and its overexpression did the opposite. Hypoxia-inducible factor-1A acted as a downstream mRNA of miR-31 and its downregulation was involved in miR-31-regulated neuronal cell injury. Vascular endothelial growth factor A level was elevated by traumatic neuron injury or hypoxia-inducible factor-1A overexpression. Hypoxia-inducible factor-1A enhanced neuronal cell injury via promoting vascular endothelial growth factor A expression. Furthermore, miR-31/hypoxia-inducible factor-1A/vascular endothelial growth factor A regulated PI3K/AKT/mTOR pathway in neuronal cells. Our study demonstrated miR-31 inhibited neuronal cell apoptosis via regulating hypoxia-inducible factor-1A/vascular endothelial growth factor A axis.

Resveratrol has been reported as an ideal medicine in the treatment of colorectal cancer. Meanwhile, cadmium could affect the occurrence and development of tumors in various ways. Epithelial–mesenchymal transition is a major progress regulated with colorectal cancer (CRC). We aimed to determine the effect and mechanism of resveratrol on the Cd-promoted EMT in CRC cells. First, we investigated the migration and invasion of CRC cells with or without the treatment of different concentrations of Cd in vitro by the transwell assay. Second, Western blot and RT-qPCR assay were used to detect the expressions of EMT-related markers (ZEB1, vimentin, E-cadherin, and N-cadherin) in Cd-exposed CRC cells. Subsequently, after treating with different concentrations of resveratrol, the migration and invasion of Cd-exposed CRC cells were detected again, as well as the expressions of EMT-related markers. Moreover, m6A-related RNAs in Cd-exposed CRC cells after treating with resveratrol were immunoprecipitated and validated by Me-RIP and RT-qPCR. These indicated that Cd promoted the migration and invasion of CRC cells. In addition, Cd up-regulated the expressions of N-cadherin, vimentin, and ZEB1, while it down-regulated that of E-cadherin in CRC cells. Resveratrol could reverse the Cd-promoted migration, invasion, and EMT procession by regulating the expression of ZEB1.

SARS‐CoV‐2 is an emerging coronavirus that causes dysfunctions in multiple human cells and tissues. Studies have looked at the entry of SARS‐CoV‐2 into host cells mediated by the viral spike protein and human receptor ACE2. However, less is known about the cellular immune responses triggered by SARS‐CoV‐2 viral proteins. Here, we show that the nucleocapsid of SARS‐CoV‐2 inhibits host pyroptosis by blocking Gasdermin D (GSDMD) cleavage. SARS‐CoV‐2‐infected monocytes show enhanced cellular interleukin‐1β (IL‐1β) expression, but reduced IL‐1β secretion. While SARS‐CoV‐2 infection promotes activation of the NLRP3 inflammasome and caspase‐1, GSDMD cleavage and pyroptosis are inhibited in infected human monocytes. SARS‐CoV‐2 nucleocapsid protein associates with GSDMD in cells and inhibits GSDMD cleavage in vitro and in vivo. The nucleocapsid binds the GSDMD linker region and hinders GSDMD processing by caspase‐1. These insights into how SARS‐CoV‐2 antagonizes cellular inflammatory responses may open new avenues for treating COVID‐19 in the future., Despite caspase‐1 and NLRP3 inflammasome activation, pyroptotic cell death of SARS‐CoV2‐infected human monocytes is prevented by cleavage site masking in the key effector GSDMD by a viral protein.

Background: Poor time in therapeutic range (TTR) control is associated with an increased risk of stroke and bleeding in atrial fibrillation (AF) patients receiving warfarin. This study aimed to determine whether the physician–pharmacist collaborative clinic (PPCC) model could improve the anticoagulation quality as well as to create a nomogram for predicting anticoagulation quality in AF patients.Methods: This retrospective observational study enrolled AF patients who either initially received warfarin or returned to warfarin after withdrawal between January 1, 2016 and January 1, 2021, at our institution. The primary outcome was dynamic changes in TTRs (a TTR of ≥60% considered high anticoagulation quality). The secondary outcomes were thromboembolic and bleeding events during follow-up. We compared the dynamic changes in TTRs between the general clinic (GC) and PPCC groups in both the original and propensity score matching (PSM) cohorts. In addition, we explored the potential predictors of high anticoagulation quality and subsequently formulated a nomogram to predict anticoagulation quality.Results: A total of 265 patients with AF were included, comprising 57 patients in the PPCC group and 208 patients in the GC group. During a median follow-up period of 203 days, the PPCC group had a shorter time (76 vs. 199 days, p < 0.001) and more patients achieved a TTR ≥60% (73.7 vs. 47.1%, p = 0.002 by log-rank test) than the GC group. The results from the PSM cohort confirmed this finding. No significant differences in the incidences of thromboembolic events (5.3 vs. 5.3%, p = 1.000) and bleeding events (4.3 vs. 3.5%, p = 1.000) were observed between the two groups. Four variables were explored as predictors related to high anticoagulation quality: treatment within a PPCC, history of bleeding, history of bleeding, and the presence of more than four comorbidities. The nomogram revealed a moderate predictive ability (c-index: 0.718, 95% confidence interval (95%CI): 0.669–0.767) and a moderately fitted calibration curve.Conclusion: The PPCC model contributed to improved anticoagulation quality in AF patients receiving warfarin. The nomogram might be an effective tool to predict anticoagulation quality and could aid physicians and pharmacists in the selection of patients who will likely benefit from sustained and active intervention.

The application of indocyanine green (ICG) imaging in laparoscopic radical gastrectomy is in the preliminary stages of clinical practice, and its safety and efficacy remain controversial.To investigate the safety and efficacy of ICG near-infrared tracer-guided imaging during laparoscopic D2 lymphadenectomy in patients with gastric cancer.Patients with potentially resectable gastric adenocarcinoma (clinical tumor stage cT1-cT4a, N0/+, M0) were enrolled in a prospective randomized clinical trial at a tertiary referral teaching hospital between November 2018 and July 2019. Patients were randomly assigned to the ICG group or the non-ICG group. The number of retrieved lymph nodes, rate of lymph node noncompliance, and postoperative recovery data were compared between the groups in a modified intention-to-treat analysis. Statistical analysis was performed from August to September 2019.The ICG group underwent laparoscopic gastrectomy using near-infrared imaging after receiving an endoscopic peritumoral injection of ICG to the submucosa 1 day before surgery.Total number of retrieved lymph nodes.Of 266 participants randomized, 133 underwent ICG tracer-guided laparoscopic gastrectomy, and 133 underwent conventional laparoscopic gastrectomy. After postsurgical exclusions, 258 patients were included in the modified intention-to-treat analysis, which comprised 129 patients (86 men and 43 women; mean [SD] age, 57.8 [10.7] years) in the ICG group and 129 patients (87 men and 42 women; mean [SD] age, 60.1 [9.1] years) in the non-ICG group. The mean number of lymph nodes retrieved in the ICG group was significantly more than the mean number retrieved in the non-ICG group (mean [SD], 50.5 [15.9] lymph nodes vs 42.0 [10.3] lymph nodes, respectively; P .001). Significantly more perigastric and extraperigastric lymph nodes were retrieved in the ICG group than in the non-ICG group. In addition, the mean total number of lymph nodes retrieved in the ICG group within the scope of D2 lymphadenectomy was also significantly greater than the mean number retrieved in the non-ICG group (mean [SD], 49.6 [15.0] lymph nodes vs 41.7 [10.2] lymph nodes, respectively; P .001). The lymph node noncompliance rate of the ICG group (41 of 129 patients [31.8%]) was lower than that of the non-ICG group (74 of 129 patients [57.4%]; P .001). The postoperative recovery process was comparable, and no significant difference was found between the ICG and non-ICG groups in the incidence (20 of 129 patients [15.5%] vs 21 of 129 [16.3%], respectively; P = .86) or severity of complications within 30 days after surgery.Indocyanine green can noticeably improve the number of lymph node dissections and reduce lymph node noncompliance without increased complications in patients undergoing D2 lymphadenectomy. Indocyanine green fluorescence imaging can be performed for routine lymphatic mapping during laparoscopic gastrectomy, especially total gastrectomy.ClinicalTrials.gov Identifier: NCT03050879.

Background Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus. Objectives This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus. Study design This study used an experimental design in rats. Setting The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. Methods Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM). Results The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered. Limitations The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic). Conclusion The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions. Key words Thalamic pain, cobra venom, electroacupuncture, pregabalin, indented neuronal nuclei, damaged mitochondria, dissolved endoplasmic reticulum, golgi body.

Glaucoma is characterized by retinal ganglion cell (RGC) degeneration and is the second leading cause of blindness worldwide. However, current treatments such as eye drop or surgery have limitations and do not target the loss of RGC. Regenerative therapy using embryonic stem cells (ESCs) holds a promising option, but ethical concern hinders clinical applications on human subjects. In this study, we employed spermatogonial stem cells (SSCs) as an alternative source of ESCs for cell-based regenerative therapy in mouse glaucoma model. We generated functional RGCs from SSCs with a two-step protocol without applying viral transfection or chemical induction. SSCs were first dedifferentiated to embryonic stem-like cells (SSC-ESCs) that resemble ESCs in morphology, gene expression signatures, and stem cell properties. The SSC-ESCs then differentiated toward retinal lineages. We showed SSC-ESC-derived retinal cells expressed RGC-specific marker Brn3b and functioned as bona fide RGCs. To allow in vivo RGC tracing, Brn3b-EGFP reporter SSC-ESCs were generated and the derived RGCs were subsequently transplanted into the retina of glaucoma mouse models by intravitreal injection. We demonstrated that the transplanted RGCs could survive in host retina for at least 10 days after transplantation. SSC-ESC-derived RGCs can thus potentially be a novel alternative to replace the damaged RGCs in glaucomatous retina.

To detect the changes in the liver function in both male and female OVE26 mice from young to adults for better understanding of type 1 diabetes‐induced hepatic changes, OVE26 mice and wild‐type FVB mice were raised in the same environment without any intervention, and then killed at 4, 12, 24 and 36 weeks for examining liver's general properties, including pathogenic and molecular changes. The influence of diabetes on the bodyweight of male and female mice was different. Both male and female OVE26 mice did not obtain serious liver injury or non‐alcoholic fatty liver disease, manifested by mild elevation of plasma alanine transaminase, and less liver lipid content along with significantly suppressed lipid synthesis. Uncontrolled diabetes also did not cause hepatic glycogen accumulation in OVE26 mice after 4 weeks. Oxidative stress test showed no change in lipid peroxidation, but increased protein oxidation. Changed endoplasmic reticulum stress and apoptosis along with increased antioxidant capacity was observed in OVE26 mice. In conclusion, uncontrolled type 1 diabetes did not cause hepatic lipid deposition most likely because of reduced lipids synthesis in response to insulin deficiency. Enhanced antioxidant capacity might not only prevent the occurrence of severe acute liver injury but also the self‐renewal, leading to liver dysfunction.

Peroxisomes play a central role in lipid metabolism. We previously demonstrated that Pex11a deficiency impairs peroxisome abundance and fatty acid β‐oxidation and results in hepatic triglyceride accumulation. The role of Pex11a in dyslipidaemia and obesity is investigated here with Pex11a knockout mice (Pex11a−/−). Metabolic phenotypes including tissue weight, glucose tolerance, insulin sensitivity, cholesterol levels, fatty acid profile, oxygen consumption, physical activity were assessed in wild‐type (WT) and Pex11a−/− fed with a high‐fat diet. Molecular changes and peroxisome abundance in adipose tissue were evaluated through qRT‐PCR, Western blotting, and Immunofluorescence. Pex11a−/− showed increased fat mass, decreased skeletal muscle, higher cholesterol levels, and more severely impaired glucose and insulin tolerance. Pex11a−/− consumed less oxygen, indicating a decrease in fatty acid oxidation, which is consistent with the accumulation of very long‐ and long‐chain fatty acids. Adipose palmitic acid (C16:0) levels were elevated in Pex11a−/−, which may be because of dramatically increased fatty acid synthase mRNA and protein levels. Furthermore, Pex11a deficiency increased ventricle size and macrophage infiltration, which are related to the reduced physical activity. These data demonstrate that Pex11a deficiency impairs physical activity and energy expenditure, decreases fatty acid β‐oxidation, increases de novo lipogenesis and results in dyslipidaemia and obesity.

Background: Cervical pedicle screw fixation through posterior approach has shown greater cervical stability advantage. The cervical pedicle screw fixation technique through posterior approach is demanding. The key to the technique is the choice of point and angle of screw entrance. The angle of screw placement is variable. Morphometric measurements of the cervical pedicle are a prerequisite for individualized screw. CT imaging has become the most reliable and important means to obtain cervical pedicle's measurement data and morphology in vivo. This study explores the feasibility and application of precise in vivo measurements by multi-slice computed tomography (MSCT) for individualized cervical transpedicular screw placement at C3–C7 in Chinese healthy population. Materials and Methods: 80 adults who underwent cervical examination by enhanced and nonenhanced computed tomography angiography, respectively, were selected and submitted to bone algorithm reconstruction for slice thickness and interval of 0.75 mm to acquire clear images and detailed bone structures. Simulation of individualized screw placement was performed with a 4.0 mm diameter screw with the help of postprocessing workstation. Pedicle transverse angle (PTA) and sagittal angle (PSA) were measured using the single- and double-line methods (analog nailing, 4.0 mm in diameter) in 160 pairs of C3–C7 pedicles, setting positive and negative values for cranial direction and foot side PSAs, respectively. Comparison of the measured change scope in PTA and PSA between the two methods was carried out; the range was defined as the error range. Results: Significantly, different results (P < 0.05) were obtained between the single- and double-line methods in the error ranges of PTA and PSA in C3–C7 pedicles. Interestingly, the double-line method was better in simulating the actual needs of individualized nailing. The mean values of PTA and PSA were 42.9°, 45.5°, 42.4°, 37.1°, 29.0° and 8.4°, 5.0°, −4.0°, and −7.8°, −8.1°, respectively, with the double-line method. Conclusion: MSCT reconstruction techniques can determine the direction and required parameters for individualized screw placement. In addition, accurate in vivo measurements of PTA and PSA, particularly PSA, provide the orthopedic surgeon with theoretical guidance and reliable basis in screw placement.

Excess heavy metals increase the risk of various diseases. Electronic waste (e-waste) is a potential route to heavy metal exposure, and Taizhou is a large e-waste dismantling area in China. In this study, we acquire blood samples from residents living near an e-waste recycling area (exposed group) and other residents in a selected reference area (reference group) for a comparative study in Taizhou in December 2017. Seven heavy metals, including cobalt (Co), nickel (Ni), cadmium (Cd), tin (Sn), copper (Cu), zinc (Zn), and lead (Pb) are quantitatively determined in all blood samples. It is discovered that the levels of Co, Ni, Sn, and Pb in the exposed group are higher than those in the reference group. Additionally, two crucial biomarkers of coronary heart disease (CHD), i.e., troponin (Tn) and myeloperoxidase (MPO), and two biomarkers of oxidative stress, i.e., malondialdehyde (MDA) and 8-isoprostane (8-I), are measured. We discovered that the levels of these indicators in the exposed group are significantly higher than those in the reference group. Meanwhile, both the Spearman correlation and multiple linear regression analysis show that Ni is positively correlated with Tn, MPO, 8-I, and MDA. Hence, we hypothesize that exposure to e-waste increases the risk of CHD, and that Ni is an important contributor to the initiation of the disease.

Background People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia). Methods PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex. Results Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3–406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5–417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4–1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60–2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7–50.4)]. Conclusions The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.

Background China proposed the Zero Markup Drug Policy (ZMDP), which popularized in tertiary hospitals across the country in 2017, to control drug expenditures’ rapid growth further and reduce the public’s medical burden. This study aims to evaluate the impact of ZMDP on the drug cost of chronic disease outpatients in the tertiary hospital in Chongqing. Methods We collected and described the drug-cost data for outpatients with chronic diseases in a Chongqing’s tertiary hospital from 2015 to 2019. The instantaneous and long-term changes of the outpatient volume and average drug cost after the ZMDP were evaluated using interrupted time series (ITS). We also analyzed the policy’s impact under the stratification of gender, age, and basic medical insurance types. Results A total of 350,848 outpatients were collected from January 2015 to February 2019. After the ZMDP, the outpatient volume for diabetes, hypertension, and coronary heart disease (CHD) all showed a downward trend, with a decrease of 53.04 (P = 0.012), 142.19 (P P P = 0.029), 5.87 yuan (P P = 0.036) per month, respectively. By gender, the average drug cost of diabetes in males had the most considerable instantaneous change, reducing by 51.21 yuan (P = 0.017); the decline of CHD in women is the most obvious, with an average monthly decrease of 12.51 yuan (P P = 0.030). CHD in 46–65 years old showed the most significant reduction, with an average monthly decline of 11.70 yuan (P P = 0.010). BMIUE’s CHD showed the most apparent downward trend, with an average monthly decrease of 10.02 yuan (P = 0.010). Conclusion The ITS analysis is an effective method of health policy evaluation. The implementation of the ZMDP can reduce the drug cost for chronic disease outpatients in the tertiary hospital and their economic burden. Follow-up policies still require targeted price adjustments in the health service system to adjust the drug cost-effectively.

The aim of our study was to investigate the suicide rates among childhood cancer survivors and assess factors associated with higher suicide risk. A review of data from Surveillance, Epidemiology, and End Results (SEER) program from 1975 to 2016 was performed for this study. This program is based on the US population and is supported by the US National Cancer Institute (NCI). Survivors diagnosed with childhood cancer were recorded. There were 40 suicides among 567,233 person-years, giving a suicide rate of 7.1 per 100,000 person-years. Compared with cancer diagnosed between 10 and 14 years old, survivors with cancer diagnosed between 0 and 4 years old had lower suicide risk. Females had a lower risk of suicide than males. Compared with survivors of thyroid cancer, the aHRs were 0.16 for acute lymphocytic leukemia, 0.15 for nodal Hodgkin's lymphoma, 0.14 for brain cancers and 0.09 for kidney cancers. Most suicides occurred after 15 years old. Suicide was a problem for survivors, especially those with thyroid cancer. Beside treating patients holistically, early psychological interventions such as communicating effectively, providing social support and follow-up care related to psychological health are needed.

Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.

Objective The IL‐33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL‐33/ST2 axis in neutrophil‐dominant allergic airway inflammation. Methods House‐dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil‐dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL‐33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow‐derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. Results In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL‐33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL‐33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil‐dominant allergic airway inflammation in an HDM/LPS‐induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL‐33‐ or ST2‐deficient mice tended to produce higher levels of the neutrophilic chemokine KC. Conclusions These results demonstrated that the IL‐33/ST2 axis may play a protective role in neutrophil‐dominant allergic airway inflammation., Most research on the IL‐33/ST2 axis has been conducted in type 2 immunity‐mediated eosinophilic asthma, but less research has focused on neutrophilic asthma. In this study, we found that IL‐33/ST2 axis deficiency aggravated neutrophil‐dominant allergic airway inflammation induced by house‐dust mite and lipopolysaccharide coexposure, which may account for the more proinflammatory status of IL‐33/ST2 axis‐deficient macrophages and lung epithelial cells.

Background. Perioperative topical tranexamic acid as antifibrinolytic agent is often used for total joint replacement to reduce bleeding currently. Staphylococcus aureus was the most common isolates from perioperative infection of prosthetic joint. The influence of topical application with tranexamic acid on the incidence of acute prosthetic joint infection of Staphylococcus aureus has not been clarified. Methods. Mouse model of Staphylococcus aureus knee prosthesis infection was constructed. Tranexamic acid was intra-articular injected during the perioperative period. CFU counting from tissue and implant sample was evaluated 3 days and 7 days after inoculating of Staphylococcus aureus. Bacterial growth curve, biofilm formation, aggregation, and plasmin inhibition of Staphylococcus aureus were tested with tranexamic acid added to the synovial culture medium. Results. There were no significant differences of CFU counting from tissue and implant samples in knee prosthesis infection after a single local injection of tranexamic acid at the postoperative 3 or 7 days. The amount of bacterial colonization on the surface of implant increased after 3 days’ continuous local injection of tranexamic acid. Tranexamic acid has no effect on bacterial growth at the concentration (10 mg/ml) of clinical application, but it can inhibit bacterial aggregation and mildly inhibit biofilm formation. Plasmin can significantly inhibit biofilm formation which can be revised by adding tranexamic acid. Conclusion. Although continuous local injection of tranexamic acid can promote the biofilm formation of Staphylococcus aureus on the surface of articular implant, it has clinical safety for using one single local injection of tranexamic acid during the perioperative period.

Background: The management of patients receiving warfarin is complicated. This study evaluated the anticoagulation quality of warfarin, explored potential predictors associated with poor anticoagulation quality, and elucidated the role of clinical pharmacists in the management of warfarin treatment.Methods: We retrospectively collected data on patients who either initially received warfarin or returned to warfarin after withdrawal between January 1, 2015 and January 1, 2020. The primary outcome was time in therapeutic range (TTR), and a TTR of ≥60% was considered as good anticoagulation quality. The secondary outcomes included thromboembolic and bleeding events during the follow-up. We assessed the TTR of each participant and investigated the potential predictors of poor anticoagulation quality (TTR < 60%) using logistic regression analysis. Additionally, we compared the warfarin anticoagulant quality and the incidence of clinical adverse events between atrial fibrillation patients in physician–pharmacist collaborative clinics (PPCCs) and general clinics.Results: Totally, 378 patients were included. The mean TTR of patients was 42.6 ± 29.8%, with only 32% of patients having achieved good anticoagulation quality. During a mean follow-up period of 192 ± 92 days, we found no significant differences in the incidences of thromboembolic events (5.0% vs. 5.1%, p = 0.967) and bleeding events (1.7% vs. 4.7%, p = 0.241) between patients with good and those with poor anticoagulation quality. The presence of PPCCs (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.25–0.90, p = 0.022) was an independent protective factor of poor anticoagulation quality, while the presence of more than four comorbidities (OR: 1.98, 95% CI: 1.22–3.24, p = 0.006) and an average interval of international normalized ratio monitoring of >30 days (OR: 1.74, 95% CI: 1.10–2.76, p = 0.019) were independent risk factors of poor anticoagulation quality. Compared with atrial fibrillation patients in general clinics, patients in PPCCs were found to have a significantly increased mean TTR level (48.4% ± 25.7% vs. 38.0% ± 27.6%, p = 0.014).Conclusion: The anticoagulation quality of warfarin was relatively low at our institution. The presence of more than four comorbidities and an average interval of international normalized ratio monitoring of >30 days independently contributed to poor anticoagulation quality. Meanwhile, the use of PPCC model improved the anticoagulation quality of warfarin.

Background. Clinically, the traditional Chinese medicine compound Gujiansan has been widely used in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). The present study aimed to investigate the mechanisms underlying the therapeutic effect of Gujiansan. Methods. A rat model of SANFH was established by the injection of dexamethasone (DEX) at a high dosage of 25 mg/kg/d. Then, Gujiansan was intragastrically administered for 2 weeks, 4 weeks, and 8 weeks, and histological examination of the femoral head was performed. The expression levels of related mRNAs and proteins were analyzed by qRT-PCR, Western blotting, and immunohistochemistry, and the levels of bone biochemical markers and cytokines were detected with ELISA kits. Results. Gujiansan administration ameliorated SANFH and induced the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), LC3, and Beclin-1 in the rat model in a dose- and time-dependent manner, and Gujiansan promoted osteocalcin secretion at the femoral head. In addition, Gujiansan increased the levels of bone formation- and bone resorption-specific markers (osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase-5b (TRACP-5b), N-terminal telopeptides of type I collagen (NTX-1), and C-terminal telopeptide of type I collagen (CTX-1)) and decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and CRP) in a dose- and time-dependent manner. Conclusions. Gujiansan accelerates the formation of a new bone, promotes the absorption of the damaged bone, inhibits the inflammatory response, induces autophagy of the femoral head via the HIF-1α/BNIP3 pathway, and ultimately ameliorates SANFH.

BACKGROUND: The data of anti-FXa-IIa activity detection in Asian population is insufficient, and its potential role for drug adherence evaluation in patients with direct oral anticoagulants (DOACs) remains unclear. This study carried out multi-center anti-FXa-IIa activity detection in Asian, aiming to explore its applicability in Asian population and find its role in adherence evaluation. METHODS: We assessed patients’ self-reported adherence using the Morisky, Green, and Levine Adherence Scale (MGLS) from six hospitals. Plasma samples were collected for peak and trough concentration determination, and anti-FXa-IIa chromogenic assay was conducted using rivaroxaban/dabigatran calibrators and controls. Multivariate logistic regression models, covariate adjustment and spearman’s two-tailed test were conducted in the data analysis. This study had been registered in clinical trials (NCT03666962). RESULTS: In total, 271 patients taking rivaroxaban (n=149) or dabigatran (n=122) were enrolled. Among the 271 patients assessed by MGLS questionnaire, 188 persons (69.4%) showed high adherence, 77 persons (28.4%) was in intermediate adherence group, and only 6 patients (2.2%) had low adherence. Patients are more adherent dosed once daily of rivaroxaban compared to twice daily of dabigatran: 75.6% vs. 63.6%. Anti-FXa-IIa activity had good linear correlation with routine coagulation indexes (P0.05). CONCLUSIONS: This study confirms that anti-FXa-IIa activity detection based on target drug calibrations can be used as an effective index for pharmacodynamic evaluation in Asian population, but had limited value in drug adherence evaluation for DOACs. As the limited samples, these findings could serve as a hypothesis-generating effort, and should be validated in further studies with larger sample sizes.

Notwithstanding previous studies have proved the anti-apoptotic effect of Bcl-2 associated athanogene3 (BAG3) in myocardium, the structural domains PXXP and BAG responsible for its protection are not reformed. Since BAG3 in cardiomyocytes is a new target for inhibiting apoptosis induced by hypoxia/reoxygenation (H/R) stress, we demonstrated that over-expression of BAG3 reduced the injury induced by H/R in either neonatal or adult rat cardiomyocytes (NRCMs and ARCMs, respectively) and PXXP and BAG domains play an important role in cellular protection in H/R stress. Apoptosis in cardiomyocytes induced by hypoxia-reperfusion was evaluated with propidium iodide (PI) staining, cleaved caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining in cultured NRCMS. Either increasing expression of BAG3 or its mutants was performed to manipulate the level of BAG3. Co-immunoprecipitation (Co-IP) was used to demonstrate the complex that BAG3 is binding to HSC70 and JNK. PXXP and BAG domains of BAG3 played an essential role in BAG3 attenuating cardiomyocytes apoptosis induced by H/R through the JNK signalling pathway. The cellular protection of BAG3 with its structural domain PXXP or BAG is associated with the binding with HSC70 and JNK. These results showed that the protective effect of BAG3 on apoptosis induced by H/R stress is closely related to its structural domains PXXP and BAG. The mechanism may provide a new therapeutic strategy for the patients suffering from ischemic cardiomyopathy and may be a critical role of its PXXP and BAG3 domains.

OBJECTIVE To quantitatively examine the relationship between social support and suicidal ideation (SI) among patients with cancer and identify the moderators that influence the magnitude of this association. METHODS Publications were searched in PubMed, PsycINFO, EMBASE, Cochrane Library and Chinese National Knowledge Infrastructure from database inception to May, 2020. Correlation coefficients (r) were chosen as the effect size with a random model to evaluate the overall effect size between social support and SI in patients with cancer. To assess statistical heterogeneity, we examined potential moderator variables on the social support and SI. RESULTS A total of 881 studies were identified in initial search, and twelve studies were eligible. A negative, small but significant correlation (r = -0.22, 95% CIs: -0.30,-0.14, p

Background Post-spinal anesthesia hypotension during cesarean delivery is caused by decreased systemic vascular resistance due to the blockage of the autonomic nerves, which is further worsened by inferior vena cava (IVC) compression by the gravid uterus. This study aimed to assess whether peak velocity and diameter of the IVC below the xiphoid or right common femoral vein (RCFV) in the inguinal region, as measured on ultrasound, could reflect the degree of IVC compression and further identify parturients at risk of post-spinal hypotension. Methods Fifty-six parturients who underwent elective cesarean section with spinal anesthesia were included in this study; peak velocities and anteroposterior diameters of the IVC and peak velocities and transverse diameters of the RCFV were measured using ultrasound before anesthesia. The primary outcome was the ultrasound measurements of IVC and RCFV acquired before spinal anesthesia and their association with post-spinal hypotension. Hypotension was defined as a drop in systolic arterial pressure by > 20% from the baseline. Multinomial logistic regression analysis was used to identify the association between the measurements of IVC, RCFV, and post-spinal hypotension during cesarean delivery. Receiver operating characteristic curves were used to test the abilities of the identified parameters to predict post-spinal hypotension; the areas under the curve and optimum cut-off values for the predictive parameters were calculated. Results A longer transverse diameter of the RCFV was associated with the occurrence of post-spinal hypotension (odds ratio = 2.022, 95% confidence interval [CI] 1.261–3.243). The area under the receiver operating characteristics curve for the prediction of post-spinal hypotension was 0.759 (95% CI 0.628–0.890, P = 0.001). A transverse diameter of > 12.2 mm of the RCFV could predict post-spinal hypotension during cesarean delivery. Conclusions A longer transverse diameter of RCFV was associated with hypotension and could predict parturients at a major risk of hypotension before anesthesia. Trial registration This study was registered at http://www.chictr.org.cn on 16, May, 2018. No. ChiCTR1800016163.

BackgroundAdvanced maternal aging has become a worldwide public health issue that contributes to female fertility decline and significant risk to embryo development. Despite transcriptional and epigenetic alterations reported in oocyte maturation and development, the dynamics of gene expression and DNA dynamics associated with aging remain elusive. Here we generated simultaneous transcriptome and methylome profiles of mouse oocytes during aging and maturation at single-cell and single-base resolution to examine key biological processes and identify the key targets for novel treatment options.ResultsWe report the dynamics in transcriptome and DNA methylome in mouse oocytes during maternal aging and oocyte maturation. Age-associated gene expression changes showed mitochondrial dysfunction in GV oocytes and defects of chromosome segregation and spindle assembly in MII oocytes. EIF2 signaling protein synthesis pathway was also impaired during aged oocyte maturation. Moreover, distinctive DNA methylation patterns were demonstrated during maternal aging in GV and MII oocytes. A positive correlation between gene expression and methylation in gene body was characterized. Furthermore, we identified several promising biomarkers, including IL-7, to assess oocyte quality, which are potential therapeutic targets for improve oocyte maturation. More importantly, we built the first mouse oocyte maturation and age prediction model using transcriptome data and validated its feasibility in published data.ConclusionsThis work provides a better understanding of molecular and cellular mechanisms during mouse oocyte aging, points a new direction of oocyte quality assessment, and paves the way for developing novel treatments to improve oocyte maturation and quality in the future.