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Wen-Guang Zhang,1 Jia-Wei Liu,2 Su-Yun Yang,3 Qiao-Qian Wang,4 Chen-Xing Liu,2 Yao Li2 1Department of Nursing, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 2School of Nursing, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 3Department of Nuclear Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 4Department of Hypertension, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of ChinaCorrespondence: Su-Yun YangDepartment of Nuclear Medicine, The First Hospital of Shanxi Medical University, Room 601, Unit 8, Building 1, No. 8 Wenyuan Lane, Yingze District, Taiyuan, 030000, People’s Republic of ChinaTel +8613603512029Email syy_dr09sun@163.comObjective: This study aimed to evaluate the effect of closed-loop management on nursing disruption risk.Methods: Using a quasi-experimental research method, convenient sampling was used to extract 20 nurses working at our hospital as the research objects. The control group members were selected from January to March 2018 via the traditional method, and the experimental group members were selected from April to June 2018 via the closed-loop management method. At three months before and after the implementation of the management model, a self-designed quantitative test form and satisfaction questionnaire were used to analyze the frequency of nursing disruption events, the accuracy rate of doctors’ advice, the average drug delivery time of the static distribution center, the implementation rate of personal digital assistant (PDA) code scanning, and the report rate of risk-outcome nursing disruption events.Results: After the implementation of the management model, the frequency of nursing disruptions and average drug delivery time of the static distribution center were significantly lower than before, and the differences were statistically significant (p < 0.05). Moreover, the accuracy rate of doctors’ advice, the implementation rate of PDA code scanning, and the reporting rate of risk-outcome nursing disruption events were significantly higher than before, and these differences were statistically significant as well (p < 0.05).Conclusion: The application of a closed-loop management model could significantly reduce the occurrence and optimize the outcomes of nursing disruption events and improve the work processes of medical care.Keywords: closed-loop management, nursing interruption, risk control, personal digital assistant, PDA, management mode

The newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.

The objective of this systematic review is to evaluate the safety ad feasibility of the totally implantable vascular access devices (TIVADs) flushed more than 4 weeks. We searched the following electronic databases from the date their build-up to February 2020: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL. The final selection resulted in 14 trials fulfilling the inclusion criteria and being included in our review. A pooled frequency of port-related late complications with longer flushing intervals (>4 weeks) was 8.0%, and the pooled frequency of occlusions, infections, and mechanical complications was 5.0%, 2.0%, and 3.0%, respectively. Then, we compared the frequency of port-related complications between standard and longer flushing intervals. There were no differences between the group’s changes in the frequency of total late complications, occlusions, infections, and mechanical complications. This systematic review and meta-analysis demonstrates that longer flushing intervals for ports are safe. However, more prospective, power appropriated randomized trials are needed to explore the specific flushing time for ports.

Background Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disorder induced by antiphospholipid antibodies, which occurs exceedingly rarely in pediatric population and even more rarely reported in HIV positive children. Case summary A case of 11 years old boy had a sudden onset of swelling in his left lower leg along with pain which were worsening gradually. Initially, topical ointment was applied for 1 month which were ineffective in reducing pain and swelling. Instead, the symptoms were aggravated and suddenly spread to the proximal thigh, accompanied by dyskinesia of left lower leg. Both color doppler ultrasonography and vascular CT scan of left lower leg revealed deep venous thrombosis. His serum anti-phospholipid antibodies (aPLs) were tested positive. He was a known case of HIV virological failure with substantial HIV viral load (VL) despite receiving regular antiretroviral therapy (ART). His symptoms improved after giving aggressive antithrombotic and high dose corticosteroid treatments. Conclusion When pediatric patients develop thrombotic disease, APS also needs to be ruled out. The autoantibodies levels should be routinely tested to look for recurrent thrombosis in children with HIV/AIDS.

Background: Survival outcome after developing brain metastasis is poor and there is an unmet need to identify factors that can promote brain metastasis. Granulocyte-colony stimulating factor (G-CSF) is given to support neutrophil recovery after myelosuppressive chemotherapy to some patients. However, there is emerging evidence that neutrophils can promote metastasis, including through the formation of neutrophil extracellular traps (NETs), scaffolds of chromatin with enzymes expelled from neutrophils to the extracellular space. In animal models, G-CSFs can induce NETs to promote liver and lung metastasis. The primary objective of this study was to test the association between G-CSF use and the later incidence of brain metastasis. Methods: Patients with de novo Stage IV breast cancer, without known brain metastasis at the time of initial diagnosis, were identified from electronic medical records covering the period from 1/1/2013 to 12/31/2020 at Northwell Health. Univariate and multivariate logistic regression models were used to test the association between variables of interest, including G-CSF use, and brain metastasis. Results: A total of 78 patients were included in the final analysis. Among those 78 patients, 24 patients (30.8%) had received G-CSF along with chemotherapy at least once. In logistic regression models, G-CSF use was not a significant factor to predict brain metastasis (OR 1.89 [95%CI 1.89-5.33]; P=0.23). Interestingly, in multivariate logistic models, pulmonary embolism (PE)/deep venous thrombosis (DVT) was a significant predictive factor of brain metastasis (OR 6.74 [95%CI 1.82-25.01]; P=0.004) (38.5% vs 21.5%). Conclusions: The use of G-CSF was not associated with increased risk of brain metastasis in patients with de novo Stage IV breast cancer. Interestingly, PE/DVT, which can be associated with elevated NETs, was associated with brain metastasis. Further studies are warranted to determine whether DVT/PE with or without elevated NETs levels in the blood, is predictive of developing brain metastasis in patients with de novo Stage IV breast cancer.

The aim of this study was to compare the short-term outcomes between laparoscopic liver resection (LLR) and open liver resection (OLR) in elderly patients with hepatic tumors.From January 2013 to December 2019, a retrospective study was conducted for a total of 143 patients with over 70 years of age, who underwent liver resection for hepatic tumors. Forty-five patients who received biliary reconstruction at the same time were excluded. According to surgical approaches, 98 patients were classified into LLR and OLR groups. All postoperative complications were classified according to the Clavien-Dindo grading system and the Comprehensive Complication Index (CCI).Incidence of the postoperative complications was not statistically different between LLR and OLR groups. The CCI was significantly lower in the LLR group, with a median of 8.556, and a median of 19.698 in the OLR group (LLR is safe and feasible as a treatment for hepatic tumor in elderly patients with potentially less postoperative complications compared to OLR.

Summary Nurses’ work-related fatigue has been recognized as a threat to nurse health and patient safety. The aim of this study was to assess the prevalence of fatigue among first-line nurses combating with COVID-19 in Wuhan, China, and to analyze its influencing factors on fatigue. A multi-center, descriptive, cross-sectional design with a convenience sample was used. The statistical population consisted of the first-line nurses in 7 tertiary general hospitals from March 3, 2020 to March 10, 2020 in Wuhan of China. A total of 2667 samples from 2768 contacted participants completed the investgation, with a response rate of 96.35%. Social-demographic questionnaire, work-related questionnaire, Fatigue Scale-14, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Chinese Perceived Stress Scale were used to conduct online survey. The descriptive statistic of nurses’ social-demographic characteristics was conducted, and the related variables of work, anxiety, depression, perceived stress and fatigue were analyzed by t-tests, nonparametric test and Pearson’s correlation analysis. The significant factors which resulted in nurses’ fatigue were further analyzed by multiple linear regression analysis. The median score for the first-line nurses’ fatigue in Wuhan was 4 (2, 8). The median score of physical and mental fatigue of them was 3 (1, 6) and 1 (0, 3) respectively. According to the scoring criteria, 35.06% nurses (n=935) of all participants were in the fatigue status, their median score of fatigue was 10 (8, 11), and the median score of physical and mental fatigue of them was 7 (5, 8) and 3 (2, 4) respectively. Multiple linear regression analysis revealed the participants in the risk groups of anxiety, depression and perceived stress had higher scores on physical and mental fatigue and the statistically significant positive correlation was observed between the variables and nurses’ fatigue, the frequency of exercise and nurses’ fatigue had a statistically significant negative correlation, and average daily working hours had a significantly positive correlation with nurses’ fatigue, and the frequency of weekly night shift had a low positive correlation with nurses’ fatigue (P

Mesenchymal stem cells (MSCs) based therapies are a major field of regenerative medicine. However, the success of MSC therapy relies on the efficiency of its delivery and retention, differentiation, and secreting paracrine factors at the target sites. Recent studies show that superparamagnetic iron oxide nanoparticles (SPIONs) modulate the regenerative effects of MSCs. After interacting with the cell membrane of MSCs, SPIONs can enter the cells via the endocytic pathway. The physicochemical properties of nanoparticles, including size, surface charge (zeta-potential), and surface ligand, influence their interactions with MSC, such as cellular uptake, cytotoxicity, homing factors, and regenerative related factors (VEGF, TGF-β1). Therefore, in-depth knowledge of the physicochemical properties of SPIONs might be a promising lead in regenerative and anti-inflammation research using SPIONs mediated MSCs. In this review, recent research on SPIONs with MSCs and the various designs of SPIONs are examined and summarized. GRAPHIC ABSTRACT: A graphical abstract describes important parameters in the design of superparamagnetic iron oxide nanoparticles, affecting mesenchymal stem cells. These physicochemical properties are closely related to the mesenchymal stem cells to achieve improved cellular responses such as homing factors and cell uptake. [Image: see text]

Epigallocatechin-3-gallate (EGCG), a green tea–derived polyphenol, exhibits antitumor activities. An EGCG nanoemulsion (nano-EGCG) was prepared to improve the stability and reduce the side effects of EGCG for treatment of human lung cancer cells, and the antitumor effects were studied. The possible molecular mechanism underlying its antitumor effects on cultured human lung cancer cells was also elucidated. The antitumor effects of EGCG and nano-EGCG were determined using methylthiazolyldiphenyl-tetrazolium bromide (MTT), colony formation, migration, and invasion assays. In addition, changes in the AMP-activated protein kinase (AMPK) signaling pathway were investigated using Western blot analyses. AMPK inhibitors were used to determine the roles of the AMPK signaling pathway involved in the molecular mechanism of the nano-EGCG. Our results showed that both EGCG and nano-EGCG inhibited the growth of H1299 lung cancer cells, with half-maximal inhibitory concentrations of 36.03 and 4.71 μM, respectively. Additionally, nano-EGCG effectively suppressed lung cancer cell colony formation, migration, and invasion in a dose-dependent manner. Nano-EGCG may inhibit lung cancer cell invasion through matrix metalloproteinase (MMP)-2- and MMP-9-independent mechanisms. Furthermore, the expression of several key regulatory proteins in the AMPK signaling pathway was modulated by nano-EGCG. Nano-EGCG may inhibit lung cancer cell proliferation, colony formation, migration, and invasion through the activation of AMPK signaling pathways. This novel mechanism of nano-EGCG suggests its application in lung cancer prevention and treatment. Our results provide an experimental foundation for further research on its potential activities and effects in vivo.

OBJECTIVES To characterize the clinical course and outcome of children with status asthmaticus (SA) admitted to a pediatric intensive care unit (PICU) METHODS: All patients with SA who were admitted to a PICU from January 2003 to December 2018 were reviewed. Polymerase chain reaction (PCR) studies on nasopharyngeal aspirate for respiratory pathogens were performed from 2014 to 2018. RESULTS Sixty-seven SA admissions constituted 2.4% of total PICU admissions (n = 2788). Fifteen (22.4%) children required noninvasive ventilation (NIV), while 7 children (10%) required invasive mechanical ventilation. Nonadherence to prior asthma therapy was common. PCR was positive for enterorvirus/rhinovirus in 84% (16 out of 19) and for any virus in 95% of nasopharyngeal aspirate (NPA) samples of patients between 2014 and 2018. Over the 16-year period, increased utilization of ipratropium bromide, magnesium sulfate and NIV was noted (P

BACKGROUND Fecal metabolites are associated with gut visceral sensitivity, mucosal immune function and intestinal barrier function, all of which have critical roles in the pathogenesis of irritable bowel syndrome (IBS). However, the metabolic profile and pathophysiology of IBS are still unclear. We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea (IBS-D). AIM To investigate the fecal metabolite composition and the role of metabolites in IBS-D pathophysiology. METHODS Thirty IBS-D patients and 15 age- and sex-matched healthy controls (HCs) underwent clinical and psychological assessments, including the IBS Symptom Severity System (IBS-SSS), an Italian modified version of the Bowel Disease Questionnaire, the Bristol Stool Form Scale (BSFS), the Hospital Anxiety and Depression Scale, and the Visceral Sensitivity Index. Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator. Fecal metabolites, including amino acids and organic acids, were measured by targeted metabolomics approaches. Correlation analyses between these parameters were performed. RESULTS The patients presented with increased stool water content, more psychological symptoms and increased visceral hypersensitivity compared with the controls. In fecal metabolites, His [IBS-D: 0.0642 (0.0388, 0.1484), HC: 0.2636 (0.0780, 0.3966), P = 0.012], Ala [IBS-D: 0.5095 (0.2826, 0.9183), HC: 1.0118 (0.6135, 1.4335), P = 0.041], Tyr [IBS-D: 0.1024 (0.0173, 0.4527), HC: 0.5665 (0.2436, 1.3447), P = 0.018], Phe [IBS-D: 0.1511 (0.0775, 0.3248), HC: 0.3967 (0.1388, 0.7550), P = 0.028], and Trp [IBS-D: 0.0323 (0.0001, 0.0826), HC: 0.0834 (0.0170, 0.1759), P = 0.046] were decreased in IBS-D patients, but isohexanoate [IBS-D: 0.0127 (0.0060, 0.0246), HC: 0.0070 (0.0023, 0.0106), P = 0.028] was significantly increased. Only Tyr was mildly correlated with BSFS scores in all subjects (r = -0.347, P = 0.019). A possible potential biomarker panel was identified to correlate with IBS-SSS score (R2Adjusted = 0.693, P < 0.001). In this regression model, the levels of Tyr, Val, hexanoate, fumarate, and pyruvate were significantly associated with the symptom severity of IBS-D. Furthermore, visceral sensation, including abdominal pain and visceral hypersensitivity, was correlated with isovalerate, valerate and isohexanoate. CONCLUSION Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.

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

Di(2-ethylhexyl) phthalate (DEHP) belongs to environmental endocrine disrupting chemicals (EEDCs) and can be rapidly hydrolyzed into the ultimate toxicant mono-2-ethylhexyl phthalate (MEHP). In this study, we used 5-aminofluorescein modified MEHP (MEHP-AF) as a fluorescence tracer to explore the toxicokinetics, including toxicokinetic parameters, absorption and transport across the intestinal mucosal barrier, distribution and pathological changes of organs. While the dose was as lower than 10 mg/kg by intragastric administration, the toxicokinetic parameters obtained by fluorescence microplate method were similar to those with the literatures by chromatography. MEHP-AF can be rapidly absorbed through the intestinal mucosal barrier in rats. In situ organ distribution in mice showed that MEHP-AF was mainly concentrated in the liver, kidney and testis. Our results suggested that the fluorescence tracing technique had the advantages with easy processing, less time-consuming, higher sensitivity for the quantitative determination, In addition, this technology also avoids the interference of exogenous or endogenous DEHP and MEHP in the experimental system. It also can be utilized to the visualization detection of MEHP in situ localization in the absorption organ and the toxic target organ. The results show that this may be a more feasible MEHP toxicological research method.

PURPOSE: To identify distinguishing CT radiomic features of pancreatic ductal adenocarcinoma (PDAC) and to investigate whether radiomic analysis with machine learning can distinguish between patients who have PDAC and those who do not. MATERIALS AND METHODS: This retrospective study included contrast material–enhanced CT images in 436 patients with PDAC and 479 healthy controls from 2012 to 2018 from Taiwan that were randomly divided for training and testing. Another 100 patients with PDAC (enriched for small PDACs) and 100 controls from Taiwan were identified for testing (from 2004 to 2011). An additional 182 patients with PDAC and 82 healthy controls from the United States were randomly divided for training and testing. Images were processed into patches. An XGBoost (https://xgboost.ai/) model was trained to classify patches as cancerous or noncancerous. Patients were classified as either having or not having PDAC on the basis of the proportion of patches classified as cancerous. For both patch-based and patient-based classification, the models were characterized as either a local model (trained on Taiwanese data only) or a generalized model (trained on both Taiwanese and U.S. data). Sensitivity, specificity, and accuracy were calculated for patch- and patient-based analysis for the models. RESULTS: The median tumor size was 2.8 cm (interquartile range, 2.0–4.0 cm) in the 536 Taiwanese patients with PDAC (mean age, 65 years ± 12 [standard deviation]; 289 men). Compared with normal pancreas, PDACs had lower values for radiomic features reflecting intensity and higher values for radiomic features reflecting heterogeneity. The performance metrics for the developed generalized model when tested on the Taiwanese and U.S. test data sets, respectively, were as follows: sensitivity, 94.7% (177 of 187) and 80.6% (29 of 36); specificity, 95.4% (187 of 196) and 100% (16 of 16); accuracy, 95.0% (364 of 383) and 86.5% (45 of 52); and area under the curve, 0.98 and 0.91. CONCLUSION: Radiomic analysis with machine learning enabled accurate detection of PDAC at CT and could identify patients with PDAC. Keywords: CT, Computer Aided Diagnosis (CAD), Pancreas, Computer Applications-Detection/Diagnosis Supplemental material is available for this article. © RSNA, 2021 An earlier incorrect version of this article appeared online. This article was corrected on July 30, 2021.

Objective: Seasonal influenza associated neurological complications had high mortality and morbidity rates in children. In this study, we aimed to investigate the clinical characteristics and mortality risk factors in children with influenza-associated encephalopathy. Methods: Retrospectively analyze the clinical data, laboratory tests, and imaging examinations of 68 children diagnosed with influenza-associated encephalopathy from January 2016 to December 2019 at Guangzhou Women and Children’s Medical Center, and the cases were divided into survival and non-survival groups by disease outcome and analyzed between two groups Results: Among the 68 children with influenza-associated encephalopathy, 40 were male, and 28 were female, aged from 3 months to 13 years, of which 66.18% (45/68) were under 5 years old. Pathogenetic tests showed that influenza virus type A accounted for 63.24% (43/68), and influenza virus type B accounted for 36.76% (25/68). Typical brain MRI changes in childhood influenza-associated encephalopathy were bilateral symmetrical lesions of the thalamus, basal ganglia, brainstem, and cerebellum. 68 patients had a mortality rate of 20.59% (14/68), with a significantly higher proportion of fever peak >39°C, Acute Disturbance Of Consciousness (ADOC), and cardiac arrest in the non-survival group than in the survival group (P

Background Cytoreductive surgery (CRS) coupled with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of treatment for many cancers with peritoneal metastasis. Mitomycin-C (MMC), the most common chemotherapy utilized with HIPEC, is associated with neutropenia but the degree of hematologic toxicity is unclear when splenectomy is included as part of CRS with MMC. Case report We present an interesting case of pancytopenia following treatment with HIPEC using MMC and comment on the possible role of splenectomy in exacerbating its cytotoxic effects. Conclusion Our unique case highlights potential hematologic toxicity following MMC-HIPEC and splenectomy. It suggests that spleen removal may enhance toxicity profiles of chemotherapy such as MMC. Because MMC is the preferred agent of choice used in CRS-HIPEC, future studies should investigate optimal MMC dosing and patient selection when splenectomy is performed to balance survival benefit with hematologic toxicities.

Lymph node mapping is important in cancer immunotherapy because the morphology of lymph nodes is one of the crucial evaluation criteria of immune responses. We developed new theragnostic glycol-chitosan-coated gold nanoparticles (GC-AuNPs), which highlighted lymph nodes in ultrasound-guided photoacoustic (US/PA) imaging. Moreover, the ovalbumin epitope was conjugated GC-AuNPs (OVA-GC-AuNPs) for delivering tumor antigen to lymph node resident macrophage. In vitro studies proved the vigorous endocytosis activity of J774A.1 macrophage and consequent strong photoacoustic signals from them. The macrophages also presented a tumor antigen when OVA-GC-AuNPs were used for cellular uptake. After the lingual injection of GC-AuNPs into healthy mice, cervical lymph nodes were visible in a US/PA imaging system with high contrast. Three-dimensional analysis of lymph nodes revealed that the accumulation of GC-AuNPs in the lymph node increased as the post-injection time passed. Histological analysis showed GC-AuNPs or OVA-GC-AuNPs located in subcapsular and medullar sinuses where macrophages are abundant. Our new theragnostic GC-AuNPs present a superior performance in US/PA imaging of lymph nodes without targeting moieties or complex surface modification. Simultaneously, GC-AuNPs were able to deliver tumor antigens to cause macrophages to present the OVA epitope at targeted lymph nodes, which would be valuable for cancer immunotherapy.

Background: This study assessed the effect of a single bolus administration of lidocaine on the prevention of tourniquet-induced hypertension (TIH) and compared the effect of lidocaine to that of ketamine in patients undergoing general anesthesia.Methods: This randomized, controlled, double-blind study included 75 patients who underwent lower limb surgery using a tourniquet. The patients were administered lidocaine (1.5 mg/kg, n = 25), ketamine (0.2 mg/kg, n = 25) or placebo (n = 25). The study drugs were administered intravenously 10 min before tourniquet inflation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before tourniquet inflation, after tourniquet inflation for 60 min at 10 min intervals, and immediately after tourniquet deflation. The incidence of TIH, defined as an increase of 30% or more in SBP or DBP during tourniquet inflation, was also recorded.Results: SBP, DBP, and HR increased significantly over time in the control group compared to those in the lidocaine and ketamine groups for 60 min after tourniquet inflation (P < 0.001, P < 0.001, and P = 0.007, respectively). The incidence of TIH was significantly lower in the lidocaine (n = 4, 16%) and ketamine (n = 3, 12%) group than in the control group (n = 14, 56%) (P = 0.001). Conclusion: Single-bolus lidocaine effectively attenuated blood pressure increase due to tourniquet inflation, with an effect comparable to that of bolus ketamine.

Background Transcatheter aortic valve replacement (TAVR) has become the choice for the treatment of severe aortic stenosis(AS) patients at high surgical risk in clinical practice. This meta-analysis aimed to further investigate the effect of the relative hemodynamics and postoperative LV remodeling by TAVR and surgical aortic valve replacement(SAVR). Methods Relevant studies were identified via systematic searches of PubMed, Google Scholar, and the Cochrane database. Relevant data were pooled as weighted mean difference (WMD) or odds risk(OR), with their 95% confidence intervals (CI). A random-effect model or fixed effect model was utilized according to the results of the heterogeneity test. Results The results indicated that peak aortic pressure gradient (WMD=-3.86, 95%CI(-6.63,-1.09), P = 0.006) and left ventricular ejection fraction (LVEF%) (WMD=-0.66, 95%CI(-1.31,-0.22), P = 0.045) were lower in the TAVR group compared with the SAVR group, but there was no significant difference between TAVR group and SAVR group in effective orifice area(EOA)(WMD = 0.05, 95%CI(-0.19,0.28), P = 0.697), left ventricular mass(LVM)(WMD = 5.24, 95%CI(-10.33, 20.80), P = 0.509). Compared with SAVR group, the incidence of prosthesis-patient mismatch(PPM) was significantly lower in the TAVR group(OR = 0.37, 95% CI(0.23, 0.61), P

Pancreatic ductal adenocarcinoma (PDAC) accounts for about 3% of all cancers in the United States and about 7% of all cancer deaths. Despite the lower prevalence relative to other solid tumors, it is one of the leading causes of cancer-related death in the US. PDAC is highly resistant to chemotherapy as well as radiation therapy. Current standard-of-care chemotherapeutic regimens provide transient disease control but eventually tumors develop chemoresistance. Tumors that are deficient in DNA damage repair mechanisms such as BRCA mutants respond better to platinum-based chemotherapies. However, these tumor cells can utilize the poly adenosine diphosphate (ADP)-ribose polymerase (PARP) as a salvage DNA repair pathway to prolong survival. Hence, in the presence of BRCA mutations, the inhibition of the PARP pathway can lead to tumor cell death. This provides the rationale for using PARP inhibitors in patients with BRCA mutated PDAC. The phase III POLO trial showed a near doubling of progression-free survival (PFS) compared with placebo in advanced PDAC when a PARP inhibitor, olaparib, was used as maintenance therapy. As a result, the US Food and Drug Administration (FDA) approved olaparib as a maintenance treatment for germline BRCA mutated advanced PDAC that has not progressed on platinum-based chemotherapy. The success of olaparib in treating advanced PDAC opened the new field for utilizing PARP inhibitors in patients with DNA damage repair (DDR) gene defects. Currently, many clinical trials with various PARP inhibitors are ongoing either as monotherapy or in combination with other agents. In addition to germline/somatic BRCA mutations, some trials are enrolling patients with defects in other DDR genes such as ATM, PALB2, and CHEK2. With many ongoing PARP inhibitor trials, it is hopeful that the management of PDAC will continuously evolve and eventually lead to improved patient outcomes.

This review aimed at assessing current guidelines' methodological quality systematically for pancreatic cancer's diagnosis and to reveal the heterogeneity of the recommendations among the evaluated guidelines. A systematic search was conducted to find the latest guidelines for pancreatic cancer's diagnosis. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to assess the qualified guidelines' feature. We extracted the main recommendations for the diagnosis of pancreatic cancer from the guidelines and performed a heterogeneity evaluation. The highest-level evidence that supported these recommendations was further extracted and analysed. Nine guidelines for the diagnosis of pancreatic cancer were included in this study. Four of the guidelines had an overall score of more than 60% and thus are recommended for clinical use. Further analysis of the heterogeneity of the main recommendations for the diagnosis of pancreatic cancer in the guidelines revealed that the recommendations vary greatly among the different guidelines. The main reasons for the great differences include the neglect of symptoms and signs, great differences in the items involved in recommendations for the diagnosis of pancreatic cancer, inconsistent recommendations for some indicators (carbohydrate antigen 19-9 and ERCP), the unreasonable citation of evidence, and the failure of some recommendations to provide evidence supporting the recommendations. For most recommendations, there was a low level of evidence and a dearth of high-quality study evidence. Recommendations for pancreatic cancer diagnosis have been significantly inconsistent over the past five years. The quality of the guidelines for diagnosing pancreatic cancer also varies. The improvement by the guideline creators of the factors that contribute to the differences mentioned above will be a shortcut to update the guidelines for the diagnosis of pancreatic cancer.

Context Gemcitabine is the backbone of systemic treatment of locally advanced and metastatic intrahepatic cholangiocarcinoma. In recent literature, gemcitabine has been linked to various pulmonary side effects. Case Report We report a case of an 82-year-old male who developed acute pulmonary hypertension after receiving one cycle of gemcitabine for metastatic cholangiocarcinoma. His symptoms began with fatigue associated with shortness of breath and cough that worsened despite dose reduction. He developed new onset bilateral pulmonary effusions and an echocardiogram revealed findings consistent with pulmonary hypertension. A computed tomography (CT) angiogram was negative for pulmonary thromboembolism. Although he was promptly treated with diuretics and steroids, the patient could not tolerate any further therapy. Conclusion Gemcitabine-induced pulmonary hypertension is rare and can be challenging to diagnose, as it remains a diagnosis of exclusion. However, physicians should be vigilant of new pulmonary symptoms, as delayed treatment can cause significant patient morbidity and mortality.

Background Patients with advanced hepatocellular carcinoma (HCC) have a poor oncologic outcome. In this study, we evaluated the role and limitation of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in advanced HCC patients with Child-Pugh class A and the efficacy of liver resection subsequent to downstaging after neoadjuvant HAIC. Methods In the present retrospective study, 103 patients with advanced HCC, who underwent neoadjuvant HAIC from April 2003 to March 2015 were analyzed. Response to HAIC was evaluated by dividing time period into after 3 cycles and after 6 cycles, each defined as early and late period. Liver resection after neoadjuvant HAIC was offered in patients who were considered as possible candidates for curative resection with tumor-free margin as well as sufficient future liver remnant volume. Results The median survival time (MST) in all patients was 14 ± 1.7 months. Response rate and disease control rate were 36.3% (37) and 81.4% (83) in early period, respectively, and 26.4% (14) and 47.2% (25), in late period, respectively (P = 0.028). Twelve patients (11.7%) underwent liver resection after neoadjuvant HAIC and the MST was 37 ± 6.6 months. One-, 3-, and 5-year recurrence-free survival after liver resection were 58.3%, 36.5%, and 24.3% respectively. Liver resection was identified as the only independent prognostic factor that associated with overall survival in multivariate analysis (P = 0.002) Conclusion HAIC could be further alternative for the treatment of advanced HCC in patients with good liver function. If liver resection is possible after neoadjuvant HAIC, liver resection would provide better outcomes than HAIC alone.

Stem cells possess a promising potential in the clinical field. The application and effective delivery of stem cells to the desired target organ or site of injury plays an important role. This review describes strategies on understanding the effective delivery of stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION) using an external magnet to enhance stem cell migration in vivo and in vitro. Fourteen total publications among 174 articles were selected. Stem cell type, SPION characteristics, labeling time, and magnetic force in vivo are considered important factors affecting the effective delivery of stem cells to the homing site. Most papers reported that the efficiency was increased when magnet is applied compared to those without. Ten studies analyzed the homing competency of SPION-labeled MSCs in vitro by observing the migration of the cell toward the external magnet. In cell-based experiments, the mechanism of magnetic attraction, the kind of nanoparticles, and various stem cells were studied well. Meta-analysis has shown the mean size of nanoparticles and degree of recovery or regeneration of damaged target organs upon in vivo studies. This strategy may provide a guideline for designing studies involving stem cell homing and further expand stem cell.

BACKGROUND The tumor microenvironment in lung cancer plays an important role in tumor progression and metastasis. Bone marrow-derived mesenchymal stem cells (MSCs) co-cultured with A549 lung cancer cells show changes in morphology, increase cell proliferation, and cell migration. This study aimed to investigate the effects of Astragalus polysaccharide (APS), a traditional Chinese herbal medicine, on the changes induced in bone marrow-derived MSCs by A549 lung cancer cells in vitro. MATERIAL AND METHODS Bone marrow-derived MSCs were co-cultured with A549 cells (Co-BMSCs). Co-cultured bone marrow-derived MSCs and A549 cells treated with 50 μg/ml of APS (Co-BMSCs + APS) were compared with untreated Co-BMSCs. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay. Flow cytometry evaluated the cell cycle. Microarray assays for mRNA expression and Western blot for protein expression were used. RESULTS Compared with untreated Co-BMSCs, APS treatment of Co-BMSCs improved cell morphology, reduced cell proliferation, and inhibited cell cycle arrest. The mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-kappaB) pathway, TP53, caspase-3, acetylated H4K5, acetylated H4K8, and acetylated H3K9 were involved in the regulatory process. CONCLUSIONS APS treatment reduced cell proliferation and morphological changes in bone marrow-derived MSCs that were co-cultured with A549 lung cancer cells in vitro.

Background Community-acquired pneumonia, especially severe community-acquired pneumonia (SCAP), remains the leading cause of death in the world. Despite advances in antimicrobial therapy, the mortality rates due to SCAP have not decreased significantly since antibiotics became routinely available. Traditional Chinese medicine (TCM) has been used for treating pneumonia for thousands of years. It is popular and widely practiced in Asia. In recent decades, evidence from both clinicians and patients suggests that TCM has some beneficial effect on SCAP. Thus, this study aims to compare the efficacy of a combination of a conventional drug and TCM to the conventional drug alone, to provide a scientific basis for clinical decisions. Methods/design A prospective, multi-center, single-blinded, double-dummy, and randomized controlled clinical trial is being conducted to test the therapeutic effects of a combination of conventional medicine and TCM versus conventional medicine in the treatment of SCAP. A total of 198 patients will be enrolled in this study, with 99 in each treatment group (combination group or conventional medicine group). The TCM will be administered twice daily for 28 days. All patients will be followed for 3 months. The primary outcome measure is treatment failure, which is defined as clinical deterioration. Secondary outcome measures are time to clinical stability, length of hospital stay, in-hospital mortality, SOFA questionnaire, quality of life and cost of treatment. Discussion It is hypothesized that the combination of a conventional drug and TCM will reduce treatment failure, time to clinical stability, length hospital of stays, and in-hospital mortality, and improve the quality of life of SCAP patients. Trial registration ClinicalTrials.gov, NCT03185923. Registered on 20 June 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3005-9) contains supplementary material, which is available to authorized users.

The purpose of this study was to investigate the cardiac-differentiation potential of induced pluripotent stem cells (iPSCs) generated from human umbilical cord-derived mesenchymal cells. Spontaneous beating colonies were observed at day 7 after the sequential addition of CHIR99021 and IWP-4. The combined use of CHIR99021 and IWP-4 downregulated the expression of pluripotency markers while upregulating cardiac transcription factors and cardiomyocyte-specific markers. The derived cardiomyocytes demonstrated typical sarcomeric structures and action-potential features; most importantly, the derived cells exhibited responsiveness to β-adrenergic and muscarinic stimulations. The analyses of molecular, structural, and functional properties revealed that the derived cardiomyocytes were similar to cardiomyocytes derived from BJ foreskin fibroblast cells. In summary, our results demonstrate that functional cardiomyocytes can be generated from human umbilical cord-derived cells. The methodology described here has potential as a means for the production of functional cardiomyocytes from discarded human umbilical cord tissue.

PURPOSE This study investigated the effectiveness of meaning-centered psychotherapy (MCP), which is known to be a helpful psychotherapeutic intervention in distressing conditions, for patients with pancreatobiliary cancer. MATERIALS AND METHODS We recruited 37 patients with pancreatobiliary cancer from three university general hospitals and assessed their psychological characteristics. Patients who reported clinically significant emotional distress were recommended to undergo MCP. Patients who consented to MCP were provided four sessions of the therapy. Patient psychological characteristics were assessed again 2 months after MCP. For statistical comparison, outcome variables included anxiety, depression, mental adjustment to cancer, and quality of life (QoL), as well as the degree of stress and physical symptoms. RESULTS Sixteen patients completed the MCP and the final assessment 2 months later. In the initial assessment, the patients receiving MCP showed higher levels of anxiety and depression than those not receiving MCP, and QoL was also lower in terms of role function, emotional function, social function, and global QoL. At the 2-month follow-up, the MCP group showed a significant improvement in anxiety (p=0.007), depression (p=0.010), and anxious preoccupation (p

Ming Lei,1 Guang-Yuan Yu,2 Yong-Gang Zhao,3 Ji-Ping Wang,1 Su-Yun Feng1 1Center of Hair Transplantation, Department of Burn and Plastic Surgery, The Fourth Medical Center of the General Hospital of PLA, Beijing, People’s Republic of China; 2Department of Dermatology, The Fourth Medical Center of the General Hospital of PLA, Beijing, People’s Republic of China; 3First Department of Surgery, Beijing Armed Police Corps Hospital, Beijing, People’s Republic of ChinaCorrespondence: Ji-Ping WangCenter of Hair Transplantation, Department of Burn and Plastic Surgery, The Fourth Medical Center of the General Hospital of PLA, No. 51 of Fucheng Road, Haidian District, Beijing, 100048, People’s Republic of ChinaTel +86 10-66867304Email wangjp693587@163.comObjective: This study aims to establish the concept of invalid extraction rates in follicular unit extraction and evaluate its clinical value.Methods: The present study involved 30 patients with alopecia. Three young surgeons (nominated A, B, and C) each performed follicular unit extraction on a randomly selected portion of the donor site of each patient for ten minutes. The outcomes were separately recorded and calculated, and converted to an invalid extraction rate for each surgeon using the formula, “invalid extraction rate = 1 − successfully extracted follicular units/actually extracted units × 100%.”Results: The follicular unit invalid extraction efficiency of each surgeon gradually declined. The average efficiency level of surgeon B was evaluated as excellent, while the levels of surgeons A and C were evaluated as good.Conclusion: With experience, surgeons can speed up the process of follicular unit extraction and gradually increase performance quality through both extraction speed and success rate.Keywords: follicular unit extraction, operating level, evaluation

Background There is little evidence indicating that anatomical resection (AR) is associated with improved survival in patients with solitary hepatocellular carcinoma (HCC) who were preoperatively evaluated by positron emission tomography (PET). The aim of our study was to compare the oncologic outcomes of AR in PET-positive versus PET-negative patients with HCC. Methods From January 2007 to September 2015, 259 patients with preoperative PET underwent hepatectomy as the primary treatment for solitary HCC. Patients were divided into four groups according to PET uptake and hepatectomy type [AR or non-anatomical resection (NAR)]: Group 1 (PET-negative and AR, n=62); Group 2 (PET-negative and NAR, n= 46); Group 3 (PET-positive and AR, n=100); Group 4 (PET-positive and NAR, n=51). Results PET positivity was associated with higher protein induced by vitamin K antagonist-II (P=0.025), lager tumor size (P=0.05), microvascular invasion (MVI) (P=0.012), and portal vein invasion (P=0.031). In Kaplan-Meier analysis for RFS, Group 1 showed remarkable difference from Group 3 and Group 4 (P=0.045, P=0.023, respectively). In the PET-positive subgroup with HCC under 3 cm, AR was associated with better RFS than NAR (P=0.016). Conclusions A combination of AR and PET negativity showed good prognosis in long-term outcomes. Finally, AR can decrease the risk of tumor recurrence in patients with a solitary PET-positive HCC less than 3 cm.

Background Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. Results The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. Conclusions It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.

The purpose of this study was to systematically evaluate guidelines for surgery in patients with severe pancreatitis and to identify gaps limiting evidence-based medicine practice. A systematic search of databases and related websites was conducted to identify surgical guidelines for patients with severe pancreatitis. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The similarities among key recommendations were compared, and the evidence supporting them was extracted and analysed. Seven surgical guidelines for patients with severe pancreatitis were included. Only two guidelines, those of the World Society of Emergency Surgery (WSES) and the European Society of Gastrointestinal Endoscopy (ESGE), scored more than 60% for overall quality and were worthy of clinical recommendation. We found that the quality of the severe acute pancreatitis surgical guidelines have much room for improvement, especially in the field of application, the participation of stakeholders and editorial independence. The heterogeneity and causes of surgical recommendations were further analysed, and the latest evidence was retrieved. It was found that the surgical guidelines for severe pancreatitis lacked high-quality evidence, some of the recommendations were controversial, and evidence citation was unreasonable. The quality of surgical guidelines for patients with severe pancreatitis varies widely. In the past 5 years, the key recommendations of the surgical guidelines for severe pancreatitis have been somewhat consistent and controversial, and improvement in these existing problems and controversies will be an effective way for developers to upgrade the surgical guidelines for severe pancreatitis.

Di-2-ethylhexyl phosphate (DEHP) and its main toxic metabolite mono-2-ethylhexyl phthalate (MEHP) are the typical endocrine disrupting chemicals (EDCs) and widely affect human health. Our previous research reported that synthetic nonionic dietary emulsifier polysorbate 80 (P80, E433) had the promotional effect on the oral absorption of DEHP in rats. The aim of this study was to explore its mechanism of promoting oral absorption, focusing on the mucus barrier and mucosal barrier of the small intestine. A small molecule fluorescent probe 5-aminofluorescein-MEHP (MEHP-AF) was used as a tracker of MEHP in vivo and in vitro. First of all, we verified that P80 promoted the bioavailability of MEHP-AF in the long-term and low-dose exposure of MEHP-AF with P80 as a result of increasing the intestinal absorption of MEHP-AF. Afterwards, experimental results from Western blot, qPCR, immunohistochemistry, and immunofluorescence showed that P80 decreased the expression of proteins (mucus protein mucin-2, tight junction proteins claudin-1 and occludin) related to mucus barrier and mucosal barrier in the intestine, changed the integrity of intestinal epithelial cell, and increased the permeability of intestinal epithelial mucosa. These results indicated that P80 promoted the oral absorption of MEHP-AF by altering the intestinal mucus barrier and mucosal barrier. These findings are of great importance for assessing the safety risks of some food emulsifiers and clarifying the absorption mechanism of chemical pollutants in food, especially for EDCs.

Plantaginis Semen (PS) is well recognized in traditional Chinese medicine (TCM) and health products. Crude PS (CPS) and salt-processed CPS (SPS) are the two most commonly used decoction pieces of PS, and are included in the 2020 edition of Chinese Pharmacopoeia. Although they all have multiple effects, the mechanisms for treating diseases are different and remain unclear, the processing mechanism of SPS is also indeterminate, which hinders their clinical application to a certain extent. In order to solve these problems and further develop PS in the clinical application. Here, we used saline-loaded model rats for experiments, and utilized an integrated approach consisting of pharmacological methods and metabolomics, which could assess the diuretic impact of CPS and SPS ethanol extracts on saline-loaded rats and elucidate the underlying mechanism. The results showed that CPS and SPS both produced increased urine volume excretion and urine electrolyte excretion, but the levels of aldosterone (ALD) and aquaporin 2 (AQP2) were decreased. And 30 differential metabolites such as linoleic acid, lysoPC(O-18:0), sphingosine-1-phosphate, lysoPC(18:0) were found, mainly involving three metabolic pathways. In conclusion, CPS and SPS both have a diuretic effect, and that of SPS is better. This work investigated the possible diuretic mechanisms of CPS and SPS which may also be the mechanism of PS for anti-hypertension. In addition, a holistic approach provided novel and helpful insights into the underlying processing mechanisms of TCM.

A novel SARS-related coronavirus (SARS-CoV-2) has recently emerged as a serious pathogen that causes high morbidity and substantial mortality. However, the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood. Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.