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Objectives The present study investigated immune disorders and CCR7 expression in primary immune thrombocytopenia (ITP) patients and analyzed their changes and clinical significance before and after treatments. Methods Flow cytometry was used to detect the proportion of different immune cell subsets in the peripheral blood of 42 patients with ITP and 20 normal controls at different time points. Treatments included first-line drugs, such as glucocorticoids and intravenous immunoglobulin, and second-line therapy, such as interleukin-11 and Thrombopoietin receptor agonists (TPO-RA). Results An elevated CD4/CD8 ratio and a decreased NK cells and CD4+CD25+CD127 low regulatory T cells (Tregs) were found in pretreatment ITP patients compared to healthy controls. The newly diagnosed group had a higher CD4/CD8 ratio and more NK cells than in the relapsed group. Tregs of the remission group were higher than those of the recurrence group. The CD4+CCR7+, CD8+CCR7+, CCR7+ subset of B cells and NK cells showed higher increases in the newly diagnosed and the relapsed group compared to controls and remission group.CD4+CCR7+ and CD8+CCR7+ subset in the relapsed group were slightly higher than the newly diagnosed. The CCR7+ subsets of CD4+ T cells, CD8+ T cells, NK cells and B cells were lower in the remission group compared to the relapsed group. Higher level of the CD8+CCR7+ subset and lower NK cells were found in the remission group compared to the controls. The ratio between the CD4+CCR7+ subset and CD8+CCR7+ subset was lower in the ITP patients than in normal controls. There was a negative correlation between the CD8+CCR7+ subset and platelet count in the ITP patients. Conclusion ITP patients with CCR7 had immune disorders and high heterogeneity, and CCR7 was found to be involved in the pathogenesis of ITP. Further studies are needed to investigate the effective treatment for ITP by targeted regulation of CCR7.

Background Telemedicine helps to provide the safe management of stroke patients in the emergency department (ED) and has been used worldwide. However, we had limited experience of telestroke in Taiwan. We aimed to identify the quality of telestroke and compare it with the original face-to-face consultation model. Methods Among 178 consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (IVtPA) from January 1, 2018, to December 31, 2019, we compared two different consultation methods: face-to-face consultation and telestroke consultation. We collected data on demographics, the National Institutes of Health Stroke Scale (NIHSS) scores, Modified Rankin Scale (mRS) scores, time measurements (onset-to-arrival time, onset-to-telestroke activation time, and time of IVtPA administration (Door-to-Needle; DTN)). Results The mean age to receive a telestroke consultation was 66.6 years, 36% were female, and the median NIHSS score was 9. The median time from patient arrival to telestroke consult activation was 40 min, and the median DTN time was 11 min longer than for face-to-face consults (62 min versus 51 min, p = .01). Telestroke consultation, similar to a face-to-face consultation, resulted in safe IVtPA eligibility assessments and administration with post-thrombolysis ICH in 4% overall (4% telestroke, 3% face-to-face consultation; p = .851). The 90-day outcomes were not different for mRS score, dichotomized 0–2 (60% telestroke 59% face-to-face consultation; p = .961), or for mortality (16% telestroke, 9% face-to-face consultation; p = .292). Conclusion In the ED, consultation via the telestroke program provides equal quality to the original face-to-face consultation model to manage ischemic stroke.

Background Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects. Methods The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors. Results There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT. Conclusion For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN.

Wei-Ying Diao,1,&ast; Cheng-Long Ding,1,&ast; Bo-Yang Yuan,2 Zan Li,3 Na Sun,4 Jia-Bin Huang5 1Department of Pathology, The First Affiliated Hospital of Jiamusi University, Jimusi City, Heilongjiang Province, 154002, People’s Republic of China; 2Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Jiamusi University, Jimusi City, Heilongjiang Province, 154002, People’s Republic of China; 3Department of Analytical Chemistry Teaching and Research, Jiamusi University, Jiamusi City, Heilongjiang Province, 154002, People’s Republic of China; 4Graduate Department, Jiamusi University, Jiamusi, Heilongjiang Province, 154002, People’s Republic of China; 5Department of Geratology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang Province, 154002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia-Bin Huang Email jiadupinglu54972@163.comIntroduction: We aim to investigate the relationship between HER2 gene phenotype and clinical characteristics, distribution and prognosis of non-small cell lung cancer (NSCLC) patients.Methods: A total of 249 NSCLC patients admitted to the oncology department of our hospital from January 2015 to January 2018 were retrospectively analyzed. The clinicopathological information, CT signs, clinical efficacy and long-term prognosis were collected and compared.Results: A total of 249 NSCLC patients underwent HER2 gene testing, 21 of them (8.43%) complied with HER2 alterations [HER2 (+)], and there were significant differences in tumor stages among patients with different HER2 phenotypes (P< 0.05). Among 21 NSCLC patients with HER2 (+), HER2 gene mutation was found in 17 patients (81%), and HER2 gene amplification in 4 patients (19%). Among the HER2 mutations, 12 cases (57%) were 20 exon mutations, and 5 cases (19%) were other mutations. Analysis of CT signs showed that border lobulation/burr, necrosis sign and pleural depression were correlated with HER2 gene mutation (P< 0.05). The incidence of EGRF mutation in HER (+) patients was significantly lower than that in HER (-) patients (P< 0.05), but there was no significant difference in the incidence of ALK gene mutation among different HER phenotypes (P> 0.05). The disease control rate of HER2 (+) patients was significantly lower than that of HER2 (-) patients, and the 12-month progression-free survival rate and survival rate of HER2 (+) patients were significantly higher than those of HER2 (-) patients (P< 0.05). There was no significant difference in the incidence of ADR among HER2 patients with different phenotypes, but the incidence of ADR (adverse drug reaction) in HER2 (+) patients with Grade 3 or 4 was significantly higher than that in the control group (P< 0.05).Discussion: The incidence of HER2 gene mutations in NSCLC patients is relatively low, but it is far commoner in patients with stage IIIB∼IV, among which exon 20 mutations are the most prevalent. In CT signs, the lesion lobulated sign/spiculated sign, necrosis signs, and pleural depression signs are related to HER2 gene mutations. In addition, HER2 gene mutations play a crucial role in the clinical prognosis and treatment safety of patients.Keywords: non-small cell lung cancer, HER2 genotype, CT signs, afatinib

Objective The objective of this work was to develop a peptide production process of the exact molecular weight propitious to topical application for cosmetics and to investigate the effects of enzymolysis-derived peptide on UVB-induced photoaging rat skin. Methods The chum salmon fish skins were hydrolyzed by alkaline protease and neutral protease and spray-dried at different conditions, and three kinds of molecular weight peptide (MFSOP) were obtained. A total of 66 ICR rats (female, 20 ± 1 g) were randomly divided into eleven groups, including the normal, model, and experimental groups. The three kinds of MFSOP were dissolved at different dosages (5‰, 2.5%, and 5%) and then applied on the ICR hairless back skins prior to exposing UVB irradiation of 3000mJ/cm2 to them 4 h later. After 8 weeks, the rats were killed and the hair-shaved skins were tested for skin moisture, hyaluronic acid, hydroxyproline, antioxidant activity, and RNA expression. Results Three kinds of MFSOP were obtained, with the average molecular weights of 495.16, 1194.00, and 2032.46 Dalton, respectively. The MFSOPs, especially the MFSOP of average molecular weight of 1194.00 Dalton, played an important role in the recovery of the UVB-injured skin tissue in lock in moisture, in antioxidant activity and in promotion in collagen and elastin protein to some extent. Conclusion MFSOPs, especially MFSOP of average molecular weight of 1194.00 Dalton, derived from enzymolysis are potential materials to apply in cosmetics for the UVB9-induced anti-photoaging activity (lock in moisture, antioxidant activity, and promotion in collagen and elastin protein).

In chronic obesity, hepatocytes become insulin resistant and exert important effects on systemic metabolism. Here we show that in early onset obesity (4 weeks high-fat diet), hepatocytes secrete exosomes that enhance insulin sensitivity both in vitro and in vivo. These beneficial effects were due to exosomal microRNA miR-3075, which is enriched in these hepatocyte exosomes. FA2H is a direct target of miR-3075 and small interfering RNA depletion of FA2H in adipocytes, myocytes and primary hepatocytes leads to increased insulin sensitivity. In chronic obesity (16–18 weeks of a high-fat diet), hepatocyte exosomes promote a state of insulin resistance. These chronic obese hepatocyte exosomes do not directly cause impaired insulin signalling in vitro but do promote proinflammatory activation of macrophages. Taken together, these studies show that in early onset obesity, hepatocytes produce exosomes that express high levels of the insulin-sensitizing miR-3075. In chronic obesity, this compensatory effect is lost and hepatocyte-derived exosomes from chronic obese mice promote insulin resistance. Ji and Luo et al. show that miR-3075 in hepatocyte-derived exosomes from mice at early stages of obesity improves insulin sensitivity in chronically obese mice, while hepatocyte exosomes from chronically obese mice induce insulin resistance.

Traumatic spinal cord injury (SCI) is a devastating condition marked by permanent motor, sensory, and autonomic dysfunction, in which the inflammatory response serves an important and preventable role. High mobility group box-1 (HMGB1) is a potent regulator of inflammation in numerous acute and chronic inflammatory conditions.; however, the role of HMGB1 in SCI remains unclear. The present study aimed to characterize the temporal dynamics of HMGB1 release after SCI, to investigate the role of spinal microglia activation in mediating the effects of HMGB1 on SCI, and to explore the therapeutic potential of intrathecal anti-HMGB1 polyclonal antibody on alleviating SCI. The present study demonstrated that HMGB1 expression was increased immediately after traumatic injury of a primary spinal neuron culture. It was found that neutralizing HMGB1 significantly ameliorated SCI pathogenesis and hind limb paralysis. Moreover, the levels of a number of pro-inflammatory cytokines in the SCI lesion were reduced when local HMGB1 was blocked by anti-HMGB1 antibody. In addition, the injured neuron-derived conditioned medium increased TNF-α secretion and the NF-κB pathway in the BV2 microglia cell line via HMGB1. Collectively, these results indicated that HMGB1 served an important role in SCI inflammation and suggested the therapeutic potential of an anti-HMGB1 antibody for SCI.

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, the detection and prognosis of which are still unsatisfactory. Thus, it is essential to explore the factors that may identify ESCC and evaluate the prognosis of ESCC patients. ResultsBoth protein and mRNA expression levels of BIRC5 are upregulated in ESCC group rather than non-ESCC group (standardized mean difference > 0). BIRC5 mRNA expression is related to the age, tumor location, lymph node stage and clinical stage of ESCC patients (p < 0.05). BIRC5 expression makes it feasible to distinguish ESCC from non-ESCC (area under the curve > 0.9), and its high expression is related to poor prognosis of ESCC patients (restrictive survival time difference = -0.036, p < 0.05). BIRC5 may play an important role in ESCC by influencing the cell cycle pathway, and CDK1, MAD2L and CDC20 may be the hub genes of this pathway. The transcription factors-MAZ and TFPD1 -are likely to regulate the transcription of BIRC5, which may be one of the factors for the high expression of BIRC5 in ESCC. ConclusionsThe current study shows that upregulation of BIRC5 may have essential clinical value in ESCC, and contributes to the understanding of the pathogenesis of ESCC.

Mesothelin (MSLN) is an attractive candidate of targeted therapy for several cancers, and hence there are increasing needs to develop MSLN-targeting strategies for cancer therapeutics. Antibody–drug conjugates (ADCs) targeting MSLN have been demonstrated to be a viable strategy in treating MSLN-positive cancers. However, developing antibodies as targeting modules in ADCs for toxic payload delivery to the tumor site but not to normal tissues is not a straightforward task with many potential hurdles. In this work, we established a high throughput engineering platform to develop and optimize anti-MSLN ADCs by characterizing more than 300 scFv CDR-variants and more than 50 IgG CDR-variants of a parent anti-MSLN antibody as candidates for ADCs. The results indicate that only a small portion of the complementarity determining region (CDR) residues are indispensable in the MSLN-specific targeting. Also, the enhancement of the hydrophilicity of the rest of the CDR residues could drastically increase the overall solubility of the optimized anti-MSLN antibodies, and thus substantially improve the efficacies of the ADCs in treating human gastric and pancreatic tumor xenograft models in mice. We demonstrated that the in vivo treatments with the optimized ADCs resulted in almost complete eradication of the xenograft tumors at the treatment endpoints, without detectable off-target toxicity because of the ADCs’ high specificity targeting the cell surface tumor-associated MSLN. The technological platform can be applied to optimize the antibody sequences for more effective targeting modules of ADCs, even when the candidate antibodies are not necessarily feasible for the ADC development due to the antibodies’ inferior solubility or affinity/specificity to the target antigen.

Objectives To evaluate the utility of the splenial angle (SA), an axial angular index of lateral ventriculomegaly measured on diffusion tensor MRI color fractional anisotropy maps, in differentiating NPH from Alzheimer’s disease (AD), Parkinson’s disease (PD), and healthy controls (HC), and post-shunt changes in NPH, compared to Evans’ index and callosal angle. Methods Evans’ index, callosal angle, and SA were measured on brain MRI of 76 subjects comprising equal numbers of age- and sex-matched subjects from each cohort of NPH, AD, PD, and HC by two raters. Receiver operating characteristics (ROC) and multivariable analysis were used to assess the screening performance of each measure in differentiating and predicting NPH from non-NPH groups respectively. Temporal changes in the measures on 1-year follow-up MRI in 11 NPH patients (with or without ventriculoperitoneal shunting) were also assessed. Results Inter-rater and intra-rater reliability were excellent for all measurements (intraclass correlation coefficients > 0.9). Pairwise comparison showed that SA was statistically different between NPH and AD/PD/HC subjects (p < 0.0001). SA performed the best in predicting NPH, with an area under the ROC curve of > 0.98, and was the only measure left in the final model of the multivariable analysis. Significant (p < 0.01) change in SA was seen at follow-up MRI of NPH patients who were shunted compared to those who were not. Conclusions The SA is readily measured on axial DTI color FA maps compared to the callosal angle and shows superior performance differentiating NPH from neurodegenerative disorders and sensitivity to ventricular changes in NPH after surgical intervention. Key Points • The splenial angle is a novel simple angular radiological index proposed for idiopathic normal pressure hydrocephalus, measured in the ubiquitous axial plane on DTI color fractional anisotropy maps. • The splenial angle quantitates the compression and stretching of the posterior callosal commissural fibers alongside the distended lateral ventricles in idiopathic normal pressure hydrocephalus (NPH) using tools readily accessible in clinical practice and shows excellent test-retest reliability. • Splenial angle outperforms Evans’ index and callosal angle in predicting NPH from healthy, Parkinson’s disease, and Alzheimer’s disease subjects on ROC analysis with an area under the curve of > 0.98 and is sensitive to morphological ventricular changes in NPH patients after ventricular shunting.

Background & Aims Liver CRIg+ (complement receptor of the immunoglobulin superfamily) macrophages play a critical role in filtering bacteria and their products from circulation. Translocation of microbiota-derived products from an impaired gut barrier contributes to the development of obesity-associated tissue inflammation and insulin resistance. However, the critical role of CRIg+ macrophages in clearing microbiota-derived products from the bloodstream in the context of obesity is largely unknown. Methods We performed studies with CRIg–/–, C3–/–, cGAS–/–, and their wild-type littermate mice. The CRIg+ macrophage population and bacterial DNA abundance were examined in both mouse and human liver by either flow cytometric or immunohistochemistry analysis. Gut microbial DNA–containing extracellular vesicles (mEVs) were adoptively transferred into CRIg–/–, C3–/–, or wild-type mice, and tissue inflammation and insulin sensitivity were measured in these mice. After coculture with gut mEVs, cellular insulin responses and cGAS/STING-mediated inflammatory responses were evaluated. Results Gut mEVs can reach metabolic tissues in obesity. Liver CRIg+ macrophages efficiently clear mEVs from the bloodstream through a C3-dependent opsonization mechanism, whereas obesity elicits a marked reduction in the CRIg+ macrophage population. Depletion of CRIg+ cells results in the spread of mEVs into distant metabolic tissues, subsequently exacerbating tissue inflammation and metabolic disorders. Additionally, in vitro treatment of obese mEVs directly triggers inflammation and insulin resistance of insulin target cells. Depletion of microbial DNA blunts the pathogenic effects of intestinal EVs. Furthermore, the cGAS/STING pathway is crucial for microbial DNA–mediated inflammatory responses. Conclusions Deficiency of CRIg+ macrophages and leakage of intestinal EVs containing microbial DNA contribute to the development of obesity-associated tissue inflammation and metabolic diseases.

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = −0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan–Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study., Graphical Abtstract

This study proposes a magnetic resonance imaging (MRI) virtual reality system and uses a pulse oximeter measuring device to reduce patient’s anxiety. The research investigates the radiation of the patient’s heart rate when using the virtual reality system and degree of the individual’s perception of anxiety. In the end, a questionnaire survey is conducted to understand the patient’s views of this system.This study uses Beckett Anxiety Scale to measure the degree of patient’s anxiety. The experimental results show that the patient’s anxiety level decreased from moderate anxiety to mild anxiety and the performance of heartbeat rate is very different between before and after using VR system. According to the results of the questionnaire, how easy the system is will affect the willing of the patient to use the system. Besides, the opinion of others will affect the patient’s feeling of the useful of the system.

The screening and treatment of laryngeal squamous cell carcinoma (LSCC) still perplexes clinicians, making it necessary to explore new markers. To this end, this research examined the underlying molecular mechanism of LSCC based on high-throughput datasets (n = 249) from multiple databases. It also identified transcription factors (TFs) independently associated with LSCC prognosis. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, differential expression genes of LSCC were deemed relevant to the extracellular matrix and its related structures or pathways, suggesting that the extracellular matrix plays an important role in LSCC. At the same time, several hub genes that may also have important roles in LSCC were identified via protein–protein interaction analysis, including CDC45, TPX2, AURKA, KIF2C, NUF, MUC1, MUC7, MUC4, MUC15, and MUC21. Eight unreported LSCC prognostic TFs – BCAT1, CHD4, FOXA2, GATA6, HNF1A, HOXB13, MAFF, and TCF4 – were screened via Kaplan–Meier curves. Cox analysis determined for the first time that HOXB13 expression and gender were independently associated with LSCC prognosis. Compared to control tissues, elevated expression of HOXB13 was found in LSCC tissues (standardized mean difference = 0.44, 95% confidence interval [0.13–0.76]). HOXB13 expression also makes it feasible to screen LSCC from non-LSCC (area under the curve = 0.77), and HOXB13 may play an essential role in LSCC by regulating HOXB7. In conclusion, HOXB13 may be a novel marker for LSCC clinical screening and treatment.

Synaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRNA expression and protein levels in HCC tissues based on large-scale data and in-house immunohistochemistry (IHC). The clinical significance and risk factors for SYNJ2-related HCC cases were identified. A nomogram of prognosis was created and its performance was validated by concordance index (C-index) and shown in calibration plots. Based on the identified differentially coexpressed genes (DCGs) of SYNJ2, enriched annotations and potential pathways were predicted, and the protein interacting networks were mapped. Upregulated SYNJ2 in 3,728 HCC and 3,203 non-HCC tissues were verified and in-house IHC showed higher protein levels of SYNJ2 in HCC tissues. Pathologic T stage was identified as a risk factor. Upregulated mRNA levels and mutated SYNJ2 might cause a poorer outcome. The C-index of the nomogram model constructed by SYNJ2 level, age, gender, TNM classification, grade, and stage was evaluated as 0.643 (95%CI = 0.619–0.668) with well-calibrated plots. A total of 2,533 DCGs were extracted and mainly functioned together with SYNJ2 in metabolic pathways. Possible transcriptional axis of CTCF/POLR2A-SYNJ2/INPP5B (transcription factor-target) in metabolic pathways was discovered based on ChIP-seq datasets. In summary, transcriptional regulatory axis CTCF/POLR2A-SYNJ2 might influence SYNJ2 expression levels. Increased SYNJ2 expression level could be utilized for predicting HCC prognosis and potentially accelerates the occurrence and development of HCC via metabolic perturbations pathways., Graphical abstract

Sulfamethoxazole (SMX) is a veterinary antibiotic that is not efficiently removed from wastewater by routine treatment and therefore can be detected widely in the environment. Here, we investigated whether microbial anaerobic transformation can contribute to the removal of SMX in constructed systems. We enriched SMX-transforming mixed cultures from sediment of a constructed wetland and from digester sludge of a wastewater treatment plant. Transformation of SMX was observed in both sulfate-reducing and methanogenic cultures, whereas nitrate-reducing cultures showed no SMX transformation. In sulfate-reducing cultures, up to 90% of an initial SMX concentration of 100-250 μM was removed within 6 weeks of incubation, and the experiments demonstrated that the transformation was microbially catalyzed. The transformation products in sulfate-reducing cultures were identified as the reduced and isomerized forms of the isoxazole SMX moiety. The transformation products did not spontaneously reoxidize to SMX after oxygen exposure, and their antibacterial activity was significantly decreased compared to SMX. Population analyses in sequential transfers of the sulfate-reducing cultures revealed a community shift toward the genus Desulfovibrio. We therefore tested a deposited strain of Desulfovibrio vulgaris Hildenborough for its capacity to transform SMX and observed the same transformation products and similar transformation rates as in the enrichment cultures. Our work suggests that an initial anaerobic step in wastewater treatment can reduce the concentration of SMX in effluents and could contribute to decreased SMX concentrations in the environment.

The COVID-19 outbreak was declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Since then, the virus has spread to affect more countries worldwide. During this period, our nuclear medicine department at Singapore General Hospital segregated our staff and patients by time, by space, or both, to minimize contact and prevent spread of the virus. Necessary changes to our clinical practices and stricter infection control measures were also enforced. We share our personal experience in managing a nuclear medicine department during this epidemic.

Pulmonary embolism (PE) care has traditionally been fragmented. The newly introduced Pulmonary Embolism Response Team (PERT) model provides streamlined care based on expedient, multi-disciplinary decision-making. This study aimed to quantify the impact of PERT, as part of a hospital-wide PE treatment protocol, on clinical outcomes.Consecutive adult patients with acute PE diagnosed via computed tomography pulmonary angiogram (CTPA) were included. The PERT and treatment protocol were introduced in January 2015. Patient characteristics, therapies, quality measures of CTPA reporting, and clinical outcomes of PE patients treated for 2 years before and after implementation of these changes were evaluated. Primary endpoints were median length of stay in intensive care (ICU) and survival to discharge.A total of 321 consecutive PE patients were enrolled, of which 154 (treated in 2013-2014) and 167 (2015-2016) patients formed the historical control and study groups, respectively. Implementation of the algorithm was associated with less variance in anticoagulation and improved reporting of right heart strain parameters on CTPA. The ICU stay was reduced from a median of 5 to 2 days (p 0.01). Eligible massive PE patients receiving reperfusion increased from 30% to 92% (p = 0.01), with mean delay from diagnosis to reperfusion decreasing from 763 to 181 minutes (p 0.01). Bleeding complications were not increased, but overall survival to discharge remained unchanged.Introducing a PERT and treatment protocol reduced ICU stay, enhanced quality measures, and improved access of massive PE patients to reperfusion therapies, without increasing bleeding complications or health care costs.

Introduction The number of treatment options for myeloma and indolent lymphoma are expanding at an exponential rate, with few direct head-to-head comparisons on which to base efficacy measures. We sought to understand how patients, their caregivers and physicians weigh treatment characteristics in order to come to a decision on which treatment option to pursue. Methods Patients, their caregivers and physicians were recruited and interviewed until data saturation was reached. A qualitative, thematic analysis was done to identify themes important to each stakeholder. Results We found that, while all three groups valued efficacy the most, the consideration of other secondary characteristics of the treatment, such as cost, toxicity and logistical issues all differed subtly between the different groups. Patients valued minimising cost and toxicity, even at small trade-offs in efficacy. Caregivers and physicians valued efficacy foremost. Conclusion Acknowledging and managing these differences is paramount because they influence shared decision-making and may affect patient outcomes in the short term, as well as their more general well-being in the long term.

The antidiabetic effect of different doses of water extract (WE) and ethanol extract (EE) was tested on a high-fat diet and streptozotocin (STZ) induced diabetic rats. Parameters were evaluated with normal control (NC), diabetes mellitus control (DM), and metformin (M) groups. In the experiment, nine groups were used with eight rats in each group and three doses of each WE and EE were used, with low, medium, and high doses. The results revealed that the DM group lost a significant amount of weight, whereas the NC group's weight increased throughout the experiment. After treatment with Fomitopsis pinicola, the EE group's weight increased gradually. Liver, kidney, and pancreas weight decreased after STZ injection and returned to normal in EE treated groups. Fasting blood glucose (FBG) levels were observed to be significantly lower after F. pinicola treatment. Serum insulin levels were also restored to normal after mushroom extracts supplementation. Specifically, STZ-induced hyperglycemia was inhibited by high dose EE administration. The biochemical analysis revealed that high-dose EE treatment increased HDL-C and decreased TC, TG, and LDL-C. Results demonstrated that high-dose EE administration protected the organ tissues from oxidative stress by normalizing the antioxidant levels, and CAT, SOD, and GSH-Px suppressed the lethal effect of MDA. The study concluded that F. pinicola EE at the dose 300 mg/kg has a more hypoglycemic, hyperinsulinemic, antioxidant, and antihyperlipidemic effect than NC, DM, and M, and regulates hyperglycemia by increasing insulin secretion.

Background Modulations on gut microbiota by traditional Chinese medicines (TCMs) and their active components are emerging as potential therapeutic agents on diabetes. Litsea glutinosa is a TCM used in clinic to treat diabetes with alkaloids as the active constituents, and the Laurolitsine is the richest one. Purpose Based on that, this study was designed to identify the potential capability of Laurolitsine on alleviating Type 2 diabetes and the changes of the composition of intestinal flora related to this disease. Methods In present study, Laurolitsine was administered to diabetic mice (db/db) by daily oral gavage at doses of 50, 100 and 200 mg/kg/day for 4 weeks. The body weight, fasting blood glucose, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT), lipid metabolism of serum and liver and liver function were measured to assess the anti-hyperglycemic and anti-hyperlipidemic effects of Laurolitsine. The liver pathological changes were observed by HE staining. Meanwhile, the effects of Laurolitsine on the changes of the composition of gut microbiota in mice were investigated via metagenomic analysis. Results Experimental results show that different doses of Laurolitsine have varying degrees of hypoglycemic and hypolipidemic effects. Among them, the treatment effect of 200mg·Kg-1 is the most obvious. In addition, Laurolitsine changes the structure of intestinal microflora significantly at various taxonomical levels in the diabetic db/db mice. Conclusions These results demonstrate that Laurolitsine may regulate glucose and lipid metabolism and improve diabetes through modulating intestinal microflora of Parabacteroides and Mucispirillum, which may be acknowledged as the iconic bacteria of diabetes.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or p = 0.12) or age (≥60 or p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Introduction: Cardiovascular disease emerged as the top cause of deaths and disability in Singapore in 2018, contributing extensively to the local healthcare burden. Primary prevention identifies at-risk individuals for the swift implementation of prevention or corrective measures. This has been traditionally done using the Singapore-adapted Framingham Risk Score (SG FRS). However, its most recent recalibration was done more than a decade ago. Recent changes in patient demographics and risk factors have undermined the accuracy of SG FRS, and the rising popularity of wearable health metrics have given rise to new data types with the potential to improve risk prediction. Methods: In healthy Singaporeans enrolled in the SingHEART study (in the absence of any clinical outcomes), we investigated potential improvements in the SG FRS to predict myocardial infarction risk based on high/low classifications of the Agatston score (surrogate outcome). Logistic regression, receiver operating characteristic and net reclassification index (NRI) analyses were conducted. Results: We demonstrated a significant improvement in the area under curve (AUC) of the SG FRS (AUC=0.641) after recalibration and incorporation of additional variables (fasting glucose and wearable-derived activity levels) (AUC=0.774) (p

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains tough and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

BACKGROUND Bioactive protein hydrolysates and peptides are believed to help counteract and ameliorate physical fatigue. Fermented soybean protein peptides (FSPPs) were prepared by protease hydrolysis and microbial fermentation. The present study aimed to evaluate the anti-fatigue properties of FSPPs. RESULTS The forced swimming time in the FSPP group was 35.78% longer than the control group, the oxygen-resistant survival time of the FSPP group was significantly prolonged and the prolongation rate was 31.00%. In addition, FSPPs decreased the lactic acid (LD), blood urea nitrogen (BUN) and creatine kinase (CK) concentration by 27.47%, 25.93% and 21.70%, respectively, after treatment, while increasing the levels of liver glycogen and muscle glycogen by 93.35% and 67.31%, respectively. FSPPs can significantly increase gut microbiota diversity and regulate the species richness of gut microbiota. The results of real-time polymerase chain reaction (RT-PCR) and western blotting showed that FSPPs activate p-AMPK/PGC1-α and PI3K/Akt/mTOR signaling pathways. CONCLUSION These results indicate that treatment with FSPPs induces anti-fatigue effects, which may be due to the mediating muscle protein synthesis and participation in skeletal muscle hypertrophy, providing energy for muscle cells. FSPPs may have potential applications in the food industry as functional material additives. © 2021 Society of Chemical Industry.

Objective: We investigated whether there were sex differences in adverse reactions to an inactivated SARS-CoV-2 vaccine among medical staff in China.Methods: From 24 February to 7 March 2021 an online cross-sectional survey was conducted with a self-administered COVID-19 vaccine questionnaire among medical staff in Taizhou, China. In total, 1397 interviewees (1,107 women and 290 men) participated in the survey.Results: In our study, 178 (16.1%) women and 23 (7.9%) men reported adverse reactions following their first vaccination, and 169 (15.3%) women and 35 (12.1%) men reported adverse reactions following their second vaccination. After adjusting for confounding factors, adverse reactions to other vaccines, worry about adverse reactions, knowledge of the inactivated vaccine being used in the hospital, taking the vaccine for one's family proactively and receiving an influenza vaccination were significantly related to adverse reactions to both injections in women. In contrast, in men, concerns about adverse reactions independently increased the risk of adverse reactions following either vaccination, and a history of adverse reactions to other vaccines also increased the risk of adverse reactions to both injections.Conclusions: Sex differences in the frequency of reported adverse reactions to an inactivated SARS-CoV-2 vaccine and potential factors were demonstrated in a sample of medical staff.

Introduction Chemotherapy is a dynamic, complex process involving cross-functional healthcare teams and comprises dosing, scheduling, safety checks, compounding and administration. Coupled with team silos, legacy systems, escalating workload and cost, efficient chemotherapy delivery is increasingly challenging, resulting in negative staff and patient experience. A design thinking methodology focused on end-users is ideal for addressing complex problems with no clear best practices. Aim We hypothesized that a multidisciplinary team using a data-driven, design thinking approach to redesign chemotherapy workflows can reduce time to treatment, improve operational efficiency and staff and patient experience. Methods A process mapping exercise was undertaken to understand the chemotherapy process. Patients and staff from different job groups were shadowed. The problem statement was "60% of patients are waiting more than an hour from their appointment time to start treatment". The following examples of "how might we" questions were used for the ideation phase: 1. How might we increase advanced chemotherapy preparations (premakes) for patients? 2. How might we ensure only premakes are listed in the mornings? Separately, we also designed an anonymized database to track chemotherapy delivery and care provision outcomes by writing an algorithm to link data extracted from appointment, queue management and chemotherapy systems. New workflows were drafted, iterated, and implemented from 1 May 2020 with the following major changes: 1. No same day blood tests and chemotherapy, with physicians reminded to complete chemotherapy orders by 3pm the day before to allow advance compounding. 2. All chemotherapy regimens were consolidated into a directory containing properties like infusion duration, premake eligibility (based on drug stability and cost) and other scheduling characteristics. This was made searchable via an Excel (Microsoft, USA) algorithm, which also recommended ideal booking slots for the scheduling team. Premakes were prioritized for morning (0830 - 1030) slots. 3. Outcome targets were agreed on and tracked daily. These were made accessible to all staff via a dashboard. The workgroup met weekly to discuss targets, barriers and iterate workflows. Daily, intra-group communication was facilitated by TigerConnect (TigerConnect, USA). We included consecutive outpatients treated at our institution from 1 Jan - 27 Jul 2020. Patients were split into two groups: a historical control group (1 Jan - 30 Apr) and a post-intervention study group (1 May - 27 Jul). The primary outcome measure was the difference between appointment time and time treatment started. Secondary outcome measures included (a) proportion of premade chemotherapy; (b) number of patients starting treatment within an hour of appointment time; and (c) number of patients finishing treatment after 6pm. Continuous data are reported as median (25th-75th centile) and analysed with the Mann-Whitney U test, while categorical data were assessed with the chi-square test. Analysis was done with SPSS v22 (IBM, USA). Results Results are summarized in Table 1. From 1 Jan - 27 July 2020, 14314 treatments were completed. Of these, 5946 (41.5%) were in the 0830 - 1030 slots prioritized for premade chemotherapy. 18.8% of patients arrived after their appointment time. The proportion of premade chemotherapy increased to 70.8% from 30.6% (p The median time to start treatment decreased from 83 (51-128) minutes in the control to 49 (27-87) minutes in the study group (p The proportion of patients with morning appointments starting treatment within 1 hour of their appointment time increased to 58.4% from 31.7% (p Conclusion We have shown that a multidisciplinary group using a data-driven, design thinking approach to address team silos, reorganize and track work processes can improve the time taken to start treatment. Changes were made at no added cost to the healthcare system and using accessible software. Potential cost savings in terms of less overtime claims for staff have yet to be factored in. Addressing patient punctuality and registration and triage processes will help further decrease time to treatment. Disclosures No relevant conflicts of interest to declare.

Background Clinical trials have demonstrated that initiating oral anti-diabetic drugs (OADs) significantly reduce glycated hemoglobin (HbA1c) levels. However, variability in lifestyle modifications and OAD adherence impact on their actual effect on glycemic control. Furthermore, evidence on dose adjustments and discontinuation of OAD on HbA1c is lacking. This study aims to use real-world data to determine the effect of OAD initiation, up-titration, down-titration, and discontinuation on HbA1c levels, among Asian patients managed in primary care. Methods A retrospective cohort study over a 5-year period, from Jan 2015 to Dec 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of type 2 diabetes mellitus (T2DM) managed by a network of primary care clinics in Singapore. Nine OADs from five different classes (biguanides, sulphonyurea, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter-2 [SGLT-2] inhibitors, and alpha-glucosidase inhibitors) were evaluated. Patients were grouped into “No OAD”, “Non-titrators,” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the various OAD titrations were identified. Subsequently, a descriptive analysis of HbA1c values before and after each titration was performed to compute a mean difference for each unique titration identified. Results Among the cohort of 57,910 patients, 43,338 of them had at least one OAD titration, with a total of 76,990 pairs of HbA1c values associated with an OAD titration. There were a total of 206 unique OAD titrations. Overall, initiation of OADs resulted in a reduction of HbA1c by 3 to 12 mmol/mol (0.3 to 1.1%), respectively. These results were slightly lower than those reported in clinical trials of 6 to 14 mmol/mol (0.5 to 1.25%). The change of HbA1c levels due to up-titration, down-titration, and discontinuation were −1 to −8 mmol/mol (−0.1 to −0.7%), +1 to 7 mmol/mol (+0.1 to +0.6%), and +2 to 11 mmol/mol (+0.2 to +1.0%), respectively. The HbA1c lowering effect of initiating newer OADs, namely DPP-4 inhibitors and SGLT-2 inhibitors was 8 to 11 mmol/mol (0.7 to 0.9%) and 7 to 11 mmol/mol (0.6 to 1.0%), respectively. Conclusion The real-world data on Asians with T2DM in this study show that the magnitudes of OAD initiation and dose titration are marginally lower than the results from clinical trials. During shared decision-making in selecting treatment options, the results enable physicians to communicate realistic expectation of the effect of oral medications on the glycemic control of their patients in primary care.

This study examined the ameliorative effects of rice protein hydrolysate (RPH) on UVB irradiation-induced photodamage in Hartley guinea pigs, particularly its influence on antioxidant indicators, moisture content, hydroxyproline (HYP) content and skin histopathology. The molecular mechanisms of RPH characteristic peptides Leu-Leu-Lys (LLK), Leu-Pro-Lys (LPK), and pyroGlu-Lys (pEK) were explored, and the results showed that RPH improved antioxidant capacity, prevented the loss of both water and HYP, and provided effective protection to the skin tissue. LPK and pEK increased the expression of type I collagen by regulating the AP-1/MMP-1 (pEK) and TGF-β/Smad (LPK) signaling pathways, with the LPK exhibiting the most significant effect. These findings indicate that RPH and its characteristic peptides can play vital roles in skin protection and, thus, this study provides a theoretical basis for RPH to become a novel, functional cosmetic ingredient.

Patient similarity analytics has emerged as an essential tool to identify cohorts of patients who have similar clinical characteristics to some specific patient of interest. In this study, we propose a patient similarity measure called D3K that incorporates domain knowledge and data-driven insights. Using the electronic health records (EHRs) of 169,434 patients with either diabetes, hypertension or dyslipidaemia (DHL), we construct patient feature vectors containing demographics, vital signs, laboratory test results, and prescribed medications. We discretize the variables of interest into various bins based on domain knowledge and make the patient similarity computation to be aligned with clinical guidelines. Key findings from this study are: (1) D3K outperforms baseline approaches in all seven sub-cohorts, (2) our domain knowledge-based binning strategy outperformed the traditional percentile-based binning in all seven sub-cohorts, (3) there is substantial agreement between D3K and physicians (κ = 0.746), indicating that D3K can be applied to facilitate shared decision making. This is the first study to use patient similarity analytics on a cardiometabolic syndrome-related dataset sourced from medical institutions in Singapore. We consider patient similarity among patient cohorts with the same medical conditions to develop localized models for personalized decision support to improve the outcomes of a target patient.