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This study was to optimize the exercise preconditioning (EP) intensity in protecting from exhaustive exercise-induced cardiac injury (EECI). A total of 98 male Sprague-Dawley rats were divided into 7 groups (n ​= ​14): the control group (C), the exhaustive exercise group (EE) and the EP ​+ ​EE groups, which include the V10 (53.0%̇O2max), V15 (58.4%̇O2max), V20 (67.0%̇O2max), V26 (74.0%̇O2max) and V30 (80.0%̇O2max) groups. Except the C group, the other groups were subjected to treadmill running. The serum contents of N terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTn-I) were detected by the enzyme-linked immunosorbent assay method, ECG was recorded, heart function was detected by pressure volume catheter and the activities of mitochondrial electron transfer pathway (ET pathway) complexes I, Ⅱ and IV were measured by high-resolution respiration instrument. Compared to the EE group, the EP groups have shown decrease of NT-proBNP and cTn-I, improvement of mitochondrial respiratory function and cardiac function. Compared to other EP groups, the V26 group has shown significant decrease of myocardial enzymes and improvement of mitochondrial function. The correlation analysis showed the EP effect was proportional to EP intensity in the range of 53.0%̇O2max-74.0%̇O2max. High intensity and long duration of exhaustive exercise caused cardiac injury and EP could decrease serum level of NT-proBNP and cTn-I, improve electrical derangement and the left ventricular function, and raise the activities of ET pathway complexes I, Ⅱ and IV. The protection of EP on EECI was improved as the EP intensity was increased from 53.0%̇O2max to 74.0%̇O2max and when EP intensity was 74.0%̇O2max, the effect was the most obvious among all the setting EP groups.

IntroductionThe aim of the study was to explore the clinical efficacy and safety of intravenous thrombolysis and bridging artery thrombectomy for hyperacute ischemic stroke with unknown onset time.Material and methodsOne hundred and twenty-eight patients with hyperacute cerebral infarction and without a clear time of onset were randomly divided into intravenous thrombolysis (n = 66) and bridging artery thrombectomy groups (n = 62).ResultsIn the intravenous thrombolysis group, 37 patients’ vessels had recanalization, 32 patients’ 24-hour National Institute of Health Stroke Scale (NIHSS) score improved, and 42 patients’ 90-day modified Rankin Scale (mRS) score was good. In the bridging artery thrombectomy group, 62 patients’ vessels had recanalization, 28 patients’ 24-hour NIHSS score improved, and 38 patients’ 90-day mRS score was good.ConclusionsThe benefits and adverse events between intravenous thrombolysis and bridging artery thrombectomy for ischemic stroke with unknown time of onset are similar.

Cancer is one of the leading causes of death in the world. It is very important to find drugs with high efficiency, low toxicity, and low side effects for the treatment of cancer. Flavonoids and their derivatives with broad biological functions have been recognized as anti-tumor chemicals. 8-Formylophiopogonanone B (8-FOB), a naturally existed homoisoflavonoids with rarely known biological functions, needs pharmacological evaluation. In order to explore the possible anti-tumor action of 8-FOB, we used six types of tumor cells to evaluate in vitro effects of this agent on cell viability and tested the effects on clone formation ability, scratching wound-healing, and apoptosis. In an attempt to elucidate the mechanism of pharmacological action, we examined 8-FOB-induced intracellular oxidative stress and -disrupted mitochondrial function. Results suggested that 8-FOB could suppress tumor cell viability, inhibit cell migration and invasion, induce apoptosis, and elicit intracellular ROS production. Among these six types of tumor cells, the nasopharyngeal carcinoma CNE-1 cells were the most sensitive cancer cells to 8-FOB treatment. Intracellular ROS production played a pivotal role in the anti-tumor action of 8-FOB. Our present study is the first to document that 8-FOB has anti-tumor activity in vitro and increases intracellular ROS production, which might be responsible for its anti-tumor action. The anti-tumor pharmacological effect of 8-FOB is worthy of further investigation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious infection caused by the new coronavirus severe acute respiratory syndrome coronavirus 2. The disease was first identified in December 2019 and has caused significant morbidity and mortality worldwide. AIM: To explore the clinical characteristics and treatments for COVID-19 in the Qinghai-Tibetan Plateau Area in China. METHODS: We retrospectively analyzed the blood cell counts (neutrophils and lymphocytes), blood gas analysis, and thoracic computed tomography changes of patients from Qinghai Province before, during, and after treatment (January 23, 2020 to February 21, 2020). In addition, we summarized and analyzed the information of critical patients. All data were analyzed using SPSS 17.0 (SPSS Inc., Chicago, IL, United States). The quantitative and count variables are represented as the mean ± SD and n (%), respectively. RESULTS: The main symptoms and signs of patients with COVID-19 were fever, dry cough, cough with phlegm, difficulty breathing, and respiratory distress with a respiration rate ≥ 30 times/min, finger oxygen saturation ≤ 93% in the resting state, and oxygenation index less than 200 but greater than 100 (after altitude correction). Eighteen patients with COVID-19, of whom three were critical, and the others were in a mild condition, were included. The main manifestations included fever, dry cough, and fatigue. Three patients developed difficulty breathing and had a fever. They were eventually cured and discharged. Adjuvant examinations showed one case with reduced white cell count (6%) (< 4 × 109/L), six with reduced count of lymphocytes (33%) (< 0.8 × 109/L), and one with abnormal blood glucose level. All 18 patients were discharged, and no death occurred. CONCLUSION: Our findings provide critical insight into assessing the clinical diagnosis and treatment for COVID-19 in the Tibetan plateau area.

Background: Jian-Pi-Yi-Shen (JPYS), the traditional Chinese medicine (TCM) decoction has been commonly used to treat chronic kidney disease (CKD) and its complications such as anemia. JPYS has been previously found to induce erythropoietin (EPO) production in HEK293T cells and CKD rats. However, the mechanism of JPYS in treating anemia of CKD rats has remained largely unknown. Here, we further extend our effort to investigate the translational control of hypoxia inducible factor (HIF)-α protein via ERK signaling and the effect on iron recycling related protein expression by JPYS, thus revealing the mechanism of JPYS in correcting anemia in CKD. Methods: Experimental CKD rats with anemia were induced by 5/6 nephrectomy. Rats were administrated orally with high dose (6.0 g/kg/d) and low dose ( 1.5 g/kg/d ) of JPYS for 90 days. Serum hepcidin level was determined to evaluate iron homeostasis. Protein expressions of HIF-2α, erythropoietin (EPO), ferritin and ferroportin (FPN), as well as the phosphorylation level of extracellular signal regulated kinase 1/2 (RK1/2) were detected by Western blot. Results: Our data showed that JPYS treatment significantly ameliorated kidney function by reducing increased levels of blood urea nitrogen (BUN), serum creatinine (Scr) and the urine protein (UPRO). Periodic acid-Schiff (PAS) and Masson staining observation showed that the renal pathological damage was restored in JPYS-treated CKD rats. In parallel, JPYS markedly improved CKD anemia through up-regulation of red blood cell (RBC), hemoglobin (HGB) and haematocrit (HCT). JPYS stimulated EPO and HIF-2α protein expression in both kidney and liver of CKD rats. Furthermore, JPYS induced the phosphorylation of ERK1/2 protein. In addition, JPYS regulated protein expressions of ferritin and FPN in both liver and spleen of CKD rats, as well as serum level of hepcidin. Conclusions: JPYS induces the expression of EPO through ERK-mediated HIF-2α protein accumulation, and regulates systemic iron recycling, supporting its role in promoting erythropoiesis and improvement of anemia in CKD.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced a worldwide pandemic. The main clinical manifestations of COVID-19 patients have been fever, cough, dyspnea, and other respiratory symptoms. However, some patients’ initial symptoms have been nausea, vomiting, diarrhea and other gastrointestinal symptoms, and SARS-CoV-2 RNA could be found in their stool samples. Studies have shown that the gastrointestinal tract highly-expressed angiotensin-converting enzyme 2 is used by SARS-CoV-2 to enter cells. Therefore, exploring the damage caused by SARS-CoV-2 to the gastrointestinal tract and whether it could replicate in the gastrointestinal tract and transmit through fecal-oral route has significance for the diagnosis, treatment and prevention of COVID-19. We combined the current clinical data about COVID-19 patients with gastrointestinal symptoms as well as its pathogenic mechanism and prevention methods herein to review the relationship between the disease and gastrointestinal symptoms.

Targeting cyclin-dependent kinases (CDKs) is a promising method of therapy cancer. Unfortunately, the efficacy of CDK inhibitors in hepatocellular carcinoma (HCC) is limited, due in part to incomplete understanding of cell cycle progression and a lack of specific biomarkers to adequately identify which patients may be responsive to CDK inhibitors. In the present study, we report that MAPRE1, a gene involved in cell cycle and microtubule regulation, is significantly increased in HCC tissue, promotes HCC cell proliferation, enhances in vitro tumorigenesis, and associates with poor prognosis of HCC. We demonstrate that MAPRE1 binds with CDK2, resulting in the hyper- phosphorylation of the CDK2 Thr161 residue in HCC cells. Our findings reveal that targeting MAPRE1 might be an effective therapeutic strategy in HCC, and suggest that MAPRE1 expression might provide a promising biomarker to stratify patients with HCC who may benefit from treatment with CDK inhibitors. This article is protected by copyright. All rights reserved.

Background:. Urbanization in China is rapidly proceeding, but rural-to-urban migration and its association with overweight and obesity is not well studied. This study aimed to explore the age at arrival, duration of migration, and the corresponding association with overweight/obesity in Yi migrants in China. Methods:. A cross-sectional study was conducted in rural and urban areas in 2015 in Sichuan province, China. Demographic characteristics, lifestyle factors, and anthropometry were collected. General linear regression models were used to assess the effect of duration of migration (1–10, 11–20, 21–30, and >30 years) on body mass index (BMI). Multi-variable logistic regression was used to examine the association between duration of migration and overweight/obesity (BMI ≥ 25 kg/m2). Results:. A total of 3056 Yi people (1894 Yi farmers and 1162 Yi migrants) aged 20 to 80 years were enrolled. After adjusting for age, sex, and other potential confounders, Yi migrants had 1.71 kg/m2 (95% confidence interval [CI]: 1.36–2.06) higher BMI and a 2.13-fold (95% CI: 1.71–2.65) higher risk of overweight/obesity than Yi farmers. In Yi migrants, stratified by age at arrival, no significant association between duration of migration and overweight/obesity was observed in those who were 0 to 20 years old at arrival. In comparison, in migrants >20 years old at arrival, compared with the reference group (1–10 years), long-term migration (>30 years) was found to be associated with overweight/obesity after adjustment (odds ratio: 1.85, 95% CI: 1.04–3.29). Conclusions:. Yi migrants were observed to have greater risk of overweight/obesity than Yi farmers. In Yi migrants, the risk of overweight/obesity increased according to the duration of migration, especially in those who were older upon their arrival.

OBJECTIVE: To investigate whether salidroside (Sal) protected the rat heart from exhaustive exercise-induced injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. METHODS: Forty-eight male Sprague-Dawley rats were divided into four groups (n = 12 rats per group): the control, the exhaustive swimming (ES) group, the low-dose Sal plus acute exhaustive swimming (SLE) group, and the high-dose Sal plus acute exhaustive swimming (SHE) group. In the SLE and SHE groups, 15 and 30 mg/kg Sal were administered, respectively, once a day. The rats in the control and ES groups were administered the same amount of physiological saline, respectively, once a day. On the 14th day, the rats in the ES, SLE and SHE groups underwent exhaustive swimming training once. Then cardiac function parameters and electrocardiograms were recorded. Biomarkers of myocardial injury in the serum and oxidative stress factors in the myocardial tissue were evaluated using ELISA tests. The levels of Nrf2, nuclear Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) messenger RNA and proteins were assessed in the myocardium using q-PCR and Western blotting, respectively. RESULTS: Compared to the control group, the ES group showed remarkable increases in serum brain natriuretic peptide (BNP), cardiac troponin I (cTnI) and reactive oxygen species levels, but significant decreases in catalase and glutathione levels (p < 0.05). Compared to the ES group, the Sal treatment decreased serum BNP and cTnI levels and alleviated the changes in levels of oxidative stress-related factors. After treatment with Sal, nuclear and intracellular levels of Nrf2 protein were increased in the myocardial cells, while the level of Keap1 protein was decreased (p < 0.05). CONCLUSION: Sal protected the heart from exhaustive exerciseinduced injury, and it may improve cardiac function and cardiac bioelectricity in exhausted rats by inducing Nrf2 expression.

Objective. To investigate whether exercise preconditioning (EP) protects the rat heart from exhaustive exercise- (EE-) induced injury by inducing the PI3K-Akt signaling pathway. Methods. 84 male Sprague-Dawley rats were randomly divided into 6 groups (n = 14 rats per group): control group (Con), exhaustive exercise group (EE), exercise preconditioning group (EP), exercise preconditioning + exhaustive exercise group (EP + EE), LY294002 (PI3K inhibitor) + exercise preconditioning + exhaustive exercise group (LY + EP + EE), and LY294002 group (LY). The Con and LY did not exercise. The remaining groups were subjected to treadmill running. The structure of myocardial tissue and serum biomarkers of myocardial injury were observed. Hemodynamic parameters were recorded with a pressure-volume catheter. TUNEL assay was used to detect the apoptosis of cardiac myocytes, and the level of mitochondrial membrane permeability transforming pore (mPTP) in myocardium was evaluated using ELISA. Pathway and apoptosis-related proteins in myocardium were assessed using western blotting. Results. Compared to the Con group, the EE group showed remarkable myocardial injury, such as cardiac dysfunction and myocardial apoptosis. Compared to the EE group, the injuries in the EP + EE group were improved. EP increased the PI3K-Akt signaling pathway and regulated Bcl-2 family to decrease the mPTP openness level. However, the cardioprotective effects of EP were attenuated when pretreated with the LY294002. Conclusions. EP protected the heart from EE-induced injury, and it may improve the cardiac function and reduce the cardiomyocyte apoptosis by activating the PI3K-Akt signaling pathway.

This study included data from 81 consecutively enrolled patients with hematological diseases who had been treated with unrelated umbilical cord blood transplantation (UCBT) between September 2014 and April 2019. All patients received intense conditioning regimens with combined fludarabine and high-dose cyclophosphamide (FC) before undergoing UCBT. Sixty-seven patients received a single UCBT, and 14 patients received a double UCBT. Fifty patients were pretreated with the fludarabine, busulfan, and cyclophosphamide (FBC) protocol, while 31 patients were treated with FC before transplantation. Graft-versus-host disease (GVHD) was prevented with cyclosporine A and mycophenolate mofetil administration. According to low-resolution, human leukocyte antigen (HLA) donor-recipient matching at six sites, 53 patients had 5-6 matches, while 28 patients had 4 matches. Seventy-eight patients (96.3%) achieved complete engraftment in this study. Thirty-six patients developed acute GVHD (aGVHD). The cumulative incidence of grade I-II aGVHD at day 100 posthematopoietic stem cell transplantation was 29.6%, and the cumulative incidence of grade III-IV aGVHD was 14.8%. At the end of the follow-up, 12 patients died due to treatment-related complications, and 4 died of disease relapse after transplantation. The transplant-related deaths were due to transplant-related infection (8 of 81), GVHD (2 of 81), and organ toxicity (2 of 81). The probability of overall survival (OS) was 80.2%. A higher dose of cyclophosphamide combined with fludarabine conditioning in UCBT was an effective curative method for treatment of hematologic disorders and could enhance the engraftment of umbilical cord blood stem cells, promote post-transplant immune reconstitution, and improve OS.

Hepatocellular carcinoma (HCC) has a high mortality rate owing to its complexity. Identification of abnormally expressed genes in HCC tissues compared to those in normal liver tissues is a viable strategy for investigating the mechanisms of HCC tumorigenesis and progression as a means of developing novel treatments. A significant advantage of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) is that the data therein were collected from different independent researchers and may be integrated, allowing for a more robust data analysis. Accordingly, in the present study, the gene expression profiles for HCC and control samples were downloaded from the GEO and TCGA. Functional enrichment analysis was performed using a Metascape dataset, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/proteins (STRING) online database. The prognostic value of mRNA for HCC was assessed using the Kaplan-Meier Plotter, a public online tool. A gene mRNA heatmap and DNA amplification numbers were obtained from cBioPortal. A total of 2,553 upregulated genes were identified. Functional enrichment analysis revealed that these differentially expressed genes (DEGs) were mainly accumulated in metabolism of RNA and the cell cycle. Considering the complexity and heterogeneity of the molecular alterations in HCC, multiple genes for the prognostication of patients with HCC are more reliable than a single gene. Thus, the PPI network and univariate Cox regression analysis were applied to screen candidate genes (small nuclear ribonucleoprotein polypeptide B and B1, nucleoporin 37, Rac GTPase activating protein 1, kinesin family member 20A, minichromosome maintenance 10 replication initiation factor, ubiquitin conjugating enzyme E2 C and hyaluronan mediated motility receptor) that are associated with the overall survival and progression-free survival of patients with HCC. In conclusion, the present study identified a set of genes that are associated with overall survival and progression-free survival of patients with HCC, providing valuable information for the prognosis of HCC.

ObjectiveInflammation plays a crucial role in tumorigenesis and progression. Our purpose was to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII), and develop a nomogram to predict the cancer-specific survival (CSS) and disease-free survival (DFS) of stage I lung adenocarcinoma patients.Methods1431 patients undergoing surgical resection with pathologically confirmed stage I lung adenocarcinoma were reviewed. The optimal cut-off values for NLR, SII, and SIRI were defined by the receiver operating characteristic (ROC) curve. Cox proportional hazards regression analyses were performed to recognize factors significantly correlated with CSS and DFS to construct the nomogram. The value of adjuvant chemotherapy on model-defined high-risk and low-risk patients was further explored.ResultsThe cohort had a median follow-up time of 63 months. Multivariate analysis revealed that higher NLR (≥2.606), higher SIRI (≥0.705), higher SII (≥580.671), later T stage, histological pattern with solid or micropapillary components and radiologic features with solid nodules were significantly associated with worse CSS and DFS. The concordance index (C-index) of the nomogram established by all these factors was higher than that of the TNM staging system both in CSS (validation set 0.778 vs 0.652) and DFS (validation set 0.758 vs 0.695). Furthermore, the value of the established nomogram on risk stratification in stage I lung adenocarcinoma patients was validated.ConclusionsHigher NLR, SII and SIRI pretreatment were associated with worse survival outcomes. A practical nomogram based on these three inflammatory biomarkers may help clinicians to precisely stratify stage I lung adenocarcinoma patients into high- and low-risk and implement individualized treatment.

Trichoderma rubrum (T. rubrum) is one of the important pathogens because it is the cause of most dermatomycosis. The treatment of Trichophyton rubrum infection is time-consuming and very expensive; it is easy for the infections to reoccur, leading to therapeutic failures, persistence, and chronic infection. These issues have inspired researchers to study natural alternative therapies instead. Cnidium monnieri (L.), as a kind of traditional Chinese medicine, has a variety of pharmacological activities and a wide range of applications, so it has a high potential for researching and economic value. We detected the effect of aqueous extract of C. monnieri (L.) on the activity of T. rubrum by Cell Count Kit-8 assay (CCK-8), and we found that 128 and 256 μg/ml of aqueous extracts of C. monnieri (L.) co-cultured with T. rubrum for 24 h showed the inhibitory effect on T. rubrum. The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed that aqueous extract of C. monnieri (L.) damaged the T. rubrum. At the same time, mass spectrometry screening with T. rubrum before and after the treatment of 256 μg/ml of aqueous extracts of C. monnieri (L.) showed that 966 differentially expressed proteins were detected, including 524 upregulated differentially expressed genes (DEGs) and 442 downregulated DEGs. The most significantly downregulated protein was chitin synthase (CHS); and the results of qRT-PCR and Western blotting demonstrated that the expression level of CHS was downregulated in the 256 μg/ml group compared with the control group. The study showed that the aqueous extract of C. monnieri (L.) could destroy the morphology of mycelia and the internal structure of T. rubrum, and it could inhibit the growth of T. rubrum. The antifungal effect of aqueous extract of C. monnieri (L.) may be related to the downregulation of the expression of CHS in T. rubrum, and CHS may be one of the potential targets of its antifungal mechanism. We concluded that aqueous extract from C. monnieri (L.) may be a potential candidate for antifungal agents.

To investigate the persistence time and the effectiveness of exercise preconditioning (EP) on myocardial protection in exhausted rats from myocardial enzymes, electrocardiogram (ECG), cardiac function, and mitochondrial respiratory function after cessation of exercise training. One hundred and twelve healthy male Sprague–Dawley rats were randomly divided into seven groups (n = 16): control group (CON), exhaustive exercise (EE) group, EP group, and EE after EP (EP + EE); furthermore, EP + EE group was randomly divided into 1D, 3D, 9D, and 18D groups (1D, 3D, 9D, and 18D) and performed exhaustive treadmill exercise at a speed of 30 m/min on the 1st, 3rd, 9th, and 18th days separately after EP exercise stopped. We detected the serum contents of N-terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) by the enzyme-linked immunosorbent assays method, recorded ECG, detected heart function by pressure volume catheter, measured the respiratory rates of rat myocardial mitochondria state 3 and 4 of complex I, complex II, and IV by high-resolution breathing apparatus. EP could decrease the serum content of NT-proBNP and cTnI, improved the electrical derangement and the left ventricular function in exhausted rats. Moreover, the protective effect was more obvious in the 9th day after EP stopped, whereas it would disappear when EP stopped for more than 18 days. Compared with EE group, the respiratory rate value of myocardial mitochondrial complex increased in 1D, 3D, and 9D groups. Therefore, the protective effect of EP on the heart of exhausted rats decreased with the prolongation of stopping training time, and the effect was significant within 3 days of discontinuing training, then decreased gradually, and completely disappeared in the 18th day. EP enhanced the cardiac function in exhausted rats through raising the nicotinamide adenine diphosphate hydride (NADH) electron transport chain and increased the respiration rates of mitochondrial respiratory complex I and IV state 3, thereby improved myocardial mitochondrial respiratory function and energy metabolism.

AIMS Myeloid sarcoma (MS) is a rare extramedullary neoplasm composed of immature myeloid precursor cells thought to be a unique clinical presentation of acute myeloid leukaemia (AML). Like AML, MS has a poor prognosis, but due to the rare nature of MS there are limited studies examining potential prognostic factors. We report our institutional experience, with the aim of investigating and establishing salient clinicopathological and molecular features of MS. METHODS AND RESULTS We retrospectively examined all clinicopathological and molecular data on MS patients between 2001 and 2017 from the University of Alabama at Birmingham (UAB) electronic medical records. The UAB electronic medical records were also reviewed and compared with the literature for other potential prognostic factors. Sixty-three patients were included in the study. The median overall survival was 24 months in the group with normal karyotype and 12 months in patients with an abnormal karyotype. CONCLUSIONS We found that an abnormal karyotype was associated with a statistically significant worse prognosis.

The ovum oil of forest frog has various health beneficial functions. In the current research, we evaluated the hypolipidemic effects of the low-cholesterol ovum oil from the forest frog and its combination with stigmasterol in rats.

Inclusion complexes of three different lengths of polyamine modified β-cyclodextrins (β-CDs) (hosts 1–3) with baicalein (BC) were prepared by a solution stirring method, and characterized by UV–Vis spectroscopy, proton nuclear magnetic resonance, scanning electron microscopy, thermogravimetric analysis, and X-ray diffractometry. The results demonstrated that 1:1 inclusion complexes of hosts 1–3 with BC are present. The binding ability of hosts 1–3 towards BC increased according to the sequence H1 > H2 > H3, which was in good agreement with the decreasing chain lengths of these hosts. When compared to BC, the inclusion complexes produced 508-, 451- and 323-fold enhancement in water solubility, respectively. At low concentrations, inclusion complexes 1/BC and 3/BC were observed with a better capacity of scavenging when compared to that of free BC. These findings reflected that the complexation strengthened the antioxidant activity of BC. Moreover, the solubility in water and resistance to oxidation of hosts 1–3/BC were satisfactory, making it possible candidates for application in herbal medicine and as healthcare products.

ObjectiveAlthough research suggests a close association between maternal thyroid function and birth outcomes, no clear conclusion has been reached. We aimed to explore this potential association in a retrospective cohort study.MethodsThis study included 8985 mother–child dyads. The maternal serum free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab) concentrations and birth outcome data were reviewed from medical records. Subjects with TPO Ab concentrations of >34 and ≤34 IU/ml were classified into the TPO Ab positivity (+) and TPO Ab negativity (−) groups, respectively.ResultsCompared with subjects in the normal group (0.1 ≤ TSH < 2.5 mIU/L and TPO Ab−), those with TSH concentrations of 2.5–4.0 mIU/L and TPO Ab− had a 0.65-fold lower risk of low birth weight (LBW). In contrast, those with TSH concentrations of >4.0 mIU/L, regardless of the TPO Ab status, had a 2.01-fold increased risk of LBW. Subclinical hypothyroidism, regardless of the TPO Ab status, was associated with a 1.94-fold higher risk of LBW when compared with that in subjects with euthyroidism and TPO Ab−. No other significant associations were observed.ConclusionA maternal TSH concentration of 2.5–4.0 mIU/L was associated with a lower risk of LBW when combined with TPO Ab−, whereas subjects with a TSH concentration of >4.0 mIU/L had an increased risk of LBW. Subclinical hypothyroidism appears to be associated with a higher risk of LBW.

Huo-Xue-Jiang-Tang Yin (HXJTY) is a Chinese medicine formulation, which has been widely used for the treatment of various lipometabolism- and glycometabolism-related diseases in clinics. Currently, HXJTY is mainly prescribed to treat patients with type 2 diabetes mellitus (T2DM), yet its chemical and pharmacologic profiles remain to be elucidated. Here, the potential bioactive compound and action mechanism were investigated using chemical and network pharmacology analysis. A rapid HPLC-MS was employed to identify and quantify the component of HXJTY. On the basis of the identified chemical markers from HXJTY, a network pharmacology study, including target gene prediction and functional enrichment, was applied to screen out the main quality markers of HXJTY and explore its potential mechanism for the treatment of T2DM. The results showed that a total of 22 components were identified and quantified from HXJTY by HPLC-MS. Furthermore, 12 active components such as astragaloside IV, calycosin-7-O-β-D-glucoside, hydroxysafflor yellow A, and others were proposed as quality markers of HXJTY for treating T2DM based on network pharmacology analysis. In addition, 125 corresponding possible therapeutic target genes of T2DM were obtained. These target genes are mainly related to peptidase activity, hydrolase activity, phosphatase activity, and cofactor binding, suggesting the involvement of PI3K-Akt, MAPK, AGE-RAGE, and Rap1 signaling pathways in HXJTY-treated T2DM. Our results may provide a useful approach to identify potential quality markers and molecular mechanism of HXJTY for treating T2DM.

Along with gradually increases in mobile phone (MP) use, the mass media has played a vital role in informing the public regarding the potential health hazards of MP use. These media warnings have prompted public worries about health. The aim of the present study is to investigate the effects of media warnings about the possible health hazards of MP use on self-reported symptoms. Participants were 703 undergraduate students who volunteered to take part in an experimental study between August 2013 and July 2015. After completing baseline questionnaires containing information on demographics, MP usage and possible confounding variables, the participants were randomly clustered assigned to a video treatment group (watching a 5-min video about the possible health hazards of MP use) or a control group. Then, they completed another set of questionnaires containing 6 self-reported physical symptoms and the Beck Depression Inventory (BDI). Chi-squared tests, Mann-Whitney U-tests and logistic regression models were applied in the data analysis. Participants in the video group reported significantly more frequent headache (P = 0.01), fatigue (P = 0.00), memory loss (P = 0.03), inattention (P = 0.00), and higher level of depression (P = 0.05) than those in the control group. Additionally, the prevalence of memory loss (β = 0.071, P = 0.03) and inattention (β = 0.110, P = 0.00) were significantly higher in participants with higher level of depression who watched the video. Media warnings about the possible health hazards of MP use promote people to report physical symptoms and psychological problems. Considering this tendency, more moderate and scientific media information is needed to alleviate public worries about MP use.

The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID‐19 patients for clinical help. The clinical data of COVID‐19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID‐19 patients and explained the discharge rate and fatality rate with a single‐arm meta‐analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID‐19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C‐reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single‐arm meta‐analysis showed that the male took a larger percentage in the gender distribution of COVID‐19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID‐19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11])., Research Highlights Our study explored the clinical and epidemiological characteristics of COVID‐19 patients, and proposed the need to focus on other systemic symptoms such as the gastrointestinal tract firstly, which could be of use for clinical work.

BACKGROUND To investigate the correlation between plasma D-dimer level and severity and prognosis of patients admitted to the emergency department with trauma. METHODS A total of 168 trauma patients admitted to the department of emergency surgery of Shengzhou People's Hospital were included in this study. The general information was collected, and the plasma D-dimer level was measured within 24 hours after admission. Patients were divided into the mild traumatic group (ISS ≤ 16 points), the moderate traumatic group (16 25 points) according to the Injury Severity Score (ISS) evaluation. According to the results from a 28-day follow-up, plasma D-dimer levels were compared between the survival group and the death group. The correlation between plasma D-dimer levels and severity of trauma patients admitted to the emergency department (according to the ISS) was analyzed. The receiver operating characteristic (ROC) curve evaluated the predictive value of plasma D-dimer levels for prognosis in patients admitted to the emergency department with trauma. RESULTS Plasma D-dimer levels successively increased from the mild traumatic group (2.51 ± 0.46 mg/L), the moderate traumatic group (4.09 ± 1.00 mg/L) to the severe traumatic group (6.58 ± 1.14 mg/L) (F = 0.659, p < 0.05). Plasma D-dimer levels were significantly and positively correlated with ISSs (r = 0.720, p < 0.001). The plasma D-dimer level in the survival group (3.72 ± 1.26 mg/L) was significantly lower than that in the death group (5.19 ± 0.87 mg/L) (t = 6.251, p < 0.001). According to the Youden index, the optimal cutoff value of plasma D-dimer was 4.00 mg/L, the AUC was 0.849, the standard error was 0.034, the 95% CI was 0.783 - 0.915, the sensitivity was 0.938, and the specificity was 0.603. CONCLUSIONS Plasma D-dimer levels were positively correlated with the severity of patients with trauma admitted to the department of emergency surgery and can predict poor prognosis.

Background Even though multi-focused psychosocial residence rehabilitation intervention (MPRRI) programs are widely implemented by the Shanghai Cancer Rehabilitation Club, these programs have not been rigorously evaluated. In this study, we evaluated the effects of a 21-day MPRRI program, on the quality of life (QoL) among cancer survivors. Methods A total of 388 cancer patients were enrolled to either receive the 21-day MPRRI (n = 129) intervention or a waiting-list comparison (WLC) intervention (n = 259). The intervention group was offered community-based 21-day MPRRI program, combining supportive-expressive group, cognitive-behavioral therapy, and Guolin Qigong. QoL was measured using the European Organization for Research and Treatment Quality of Life Version 3 Questionnaire. Multivariable linear models were used to compare changes in QoL values between the two groups. Results After adjustment for the QoL score and other covariates at baseline, there was no significant difference in global health status (mean = 3.8, 95% CI − 1.3–9.0, P = 0.14) between the two groups after 6 months intervention. While compared with the WLC group, the intervention group showed significant improvements in the QoL score (all P

Flavonoids are some of the most important natural products with a variety of physiological activities. 8-Formylophiopogonanone B (8-FOB) is a naturally existing homoisoflavonoid in Ophiopogon japonicus. Paraquat (PQ) has been widely used as a potent herbicide and has high toxicity in humans. The goal of the present study was to investigate whether 8-FOB could protect against PQ-induced hepatotoxicity in vitro and in vivo. We first tested the protective effects of 8-FOB on PQ-induced cytotoxicity in L02 cells by determining cell viability, intracellular oxidative stress levels, mitochondrial function, and apoptosis in vitro. To verify the protective effects of 8-FOB, we pretreated mice with 8-FOB and assessed liver function, hepatic oxidative stress, and histopathological changes after PQ administration. Our results revealed that 8-FOB could antagonize PQ-induced hepatotoxicity in vitro and in vivo. The antagonistic effects could be attributed to suppressing oxidative stress, preserving mitochondrial function, and inhibiting apoptosis. The present study is the first to document that 8-FOB, a homoisoflavonoid compound, is an effective antioxidant for antagonizing PQ-induced hepatotoxicity.

Modern lifestyle factors (high-caloric food rich in fat) and daily chronic stress are important risk factors for metabolic disturbances. Increased hypothalamic-pituitary-adrenal (HPA) axis activity and the subsequent excess production of glucocorticoids (GCs) in response to chronic stress (CS) leads to increases in metabolic complications, such as type 2 diabetes and insulin resistance (IR). Melatonin (MLT), which protects several regulatory components of the HPA axis from GC-induced deterioration, might improve glucose homeostasis. Piromelatine is a melatonin receptor-1/melatonin receptor-2 (MT1/MT2) agonist with high affinity for MLT receptors and a longer duration of action than MLT. The objective of the present study was to explore the potential effects of piromelatine on glucose and lipid metabolism and insulin sensitivity in rats with IR induced by a high-fat diet combined with CS (CF). The results showed that piromelatine prevented the suppression of body weight gain and energy intake induced by CF and normalized CF-induced hyperglycemia and homeostasis model assessment-IR index, which suggests that piromelatine prevented whole-body IR. Piromelatine also prevented CF-induced dysregulation of genes involved in glucose and lipid metabolism, including proinflammatory cytokines, in adipose tissue. In addition, piromelatine also attenuated CF-induced excess free corticosterone release, increased glucocorticoid receptor expression, and decreased 11β-hydroxysteroid dehydrogenase-1 expression, suggesting that piromelatine might ameliorate impaired glucose metabolism and prevent IR by normalizing HPA-axis functions. In conclusion, piromelatine might be a novel therapeutic agent for glucose intolerance and IR.

The present study aimed at identifying the clinical, radiological and pathological characteristics of retroperitoneal paragangliomas, and determining the association between the tumor features and the prognosis of patients following surgery. A total of 34 patients with retroperitoneal paragangliomas, who underwent resection between November 1999 and December 2015, were included in the present retrospective study. The patients' demographics, clinical symptoms and signs, tumor functional status, surgical procedure, intraoperative results, tumor pathology, radiological results, and postoperative survival time were recorded and analyzed. Of the 34 patients, the most common type of presenting symptom was abdominal mass (46%), followed by hypertension (39%) and abdominal pain (32%). Functional tumors occurred in 20 patients (59%). Computed tomography (CT) and magnetic resonance imaging revealed soft-tissue masses, with marked enhancement in the arterial phase, indicative of retroperitoneal paragangliomas. The preoperative CT diagnostic accuracy rate between 2010 and 2015 was markedly improved, compared with that between 1999 and 2009. The tumors were primarily located close to the renal arteries and veins surrounding the abdominal aorta and inferior vena cava. With the exception of one malignant paraganglioma, the majority of paragangliomas were positive for chromogranin A, S-100 protein, vimentin and heat-shock protein 90, and exhibited decreased expression of Ki-67 antigen and insulin-like growth factor 2. All tumors were completely removed by surgery. Distant metastasis, but not tumor size, functional status and local invasion, was markedly associated with survival. The preoperative diagnostic accuracy rate of retroperitoneal paragangliomas may be improved by focusing on the predilection sites and CT characteristics. In addition, immunohistochemical markers were useful to determine tumor malignancy. Complete surgical resection was appropriate for all patients and postoperative survival time was identified to be associated with tumor metastasis.

// Xiao-Yu Chen 1 , De-Fang Li 2 , Ji-Chun Han 2 , Bo Wang 3 , Zheng-Ping Dong 2 , Li-Na Yu 2 , Zhao-Hai Pan 2 , Chuan-Jun Qu 2 , Ying Chen 2 , Shi-Guo Sun 1 , Qiu-Sheng Zheng 2 1 College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China 2 Binzhou Medical University, Yantai, Shandong, 264003, China 3 Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002, China Correspondence to: Qiu-Sheng Zheng, email: zqsyt@sohu.com Shi-Guo Sun, email: sunsg@nwsuaf.edu.cn Keywords: reprogramming, melanoma, cachexia, isoliquiritigenin, mTORC2-AKT-GSK3β signaling Received: December 08, 2016 Accepted: March 15, 2017 Published: March 29, 2017 ABSTRACT Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor activity in vitro and in vivo . The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 μg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment. In ISL-treated cells, glucose uptake, lactate levels and mRNA expression levels of GLUT1 and HK2 were significantly decreased, and accompanied by an increase in O 2 consumption rate (OCR) and adenosine triphosphate (ATP) deficiency. Protein expression levels of mTORC2-AKT-GSK3β signaling pathway components (mTOR, p-mTOR, RICTOR, p-AKT, p-GSK3β) decreased significantly after ISL treatment. Co-treatment of ISL and the mTOR-specific inhibitor Ku-0063794 had a synergistic effect on the inhibition of proliferation, and increased melanin content and TYR activity. Glucose uptake and lactate levels decreased more significantly than treatment with ISL alone. These findings indicate that ISL induced reprogramming in A375 melanoma cells by activating mTORC2-AKT-GSK3β signaling.

Epidemiologic studies are inconsistent regarding the association between plasma copeptin level and heart failure (HF). The aim of this study was to perform a meta‐analysis to determine whether high level of copeptin is correlated with incidence of HF and mortality in patients with HF. We searched PUBMED and EMBASE databases for studies conducted from 1966 through May 2016 to identify studies reporting hazard ratio (HR) estimates with 95% confidence intervals (CIs) for the association between plasma copeptin level and HF. A random‐effects model was used to combine study‐specific risk estimates. A total of 13 studies were included in the meta‐analysis, with five studies on the incidence of HF and eight studies on the mortality of patients with HF. For incidence of HF, the summary HR indicated a borderline positive association of high plasma copeptin level with HF risk (HR, 1.60; 95% CI, 0.90–2.85). Furthermore, an increase of 1 standard deviation in log copeptin level was associated with a 17% increase in the risk of incident HF (HR, 1.17; 95% CI, 1.02–1.33). For all‐cause mortality of patients with HF, we also found a significant association between elevated plasma copeptin level and increased mortality of HF (HR, 1.76; 95% CI, 1.33–2.33). Our dose–response analysis indicated that an increment in copeptin level of 1 pmol/l was associated with a 3% increase in all‐cause mortality (HR, 1.03; 95% CI, 1.01–1.05). In conclusion, our results suggest that elevated plasma copeptin level is associated with an increased risk of HF and all‐cause mortality in patients with HF.

// Zheng Ping 1 , Gene P. Siegal 1, 6 , Shuko Harada 1, 6 , Isam-Eldin Eltoum 1, 6 , Mariam Youssef 1 , Tiansheng Shen 1 , Jianbo He 3 , Yingjie Huang 7 , Dongquan Chen 4, 6 , Yiping Li 2, 6 , Kirby I Bland 5, 6 , Helena R Chang 8 , Dejun Shen 1, 6 1 Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA 2 Division of Cell and Molecular Pathology, Departments of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA 3 Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA 4 Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA 5 Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA 6 UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA 7 Ningbo Clinical and Pathological Diagnosis Center, Ningbo, Zhejiang, China 8 Revlon/UCLA Breast Center, Department of Surgery, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA Correspondence to: Dejun Shen, email: dshen@uabmc.edu Keywords: invasive lobular carcinoma, CDH1 mutation, ERBB2 mutation, genomics, TCGA Received: September 09, 2016 Accepted: October 24, 2016 Published: November 02, 2016 ABSTRACT E-cadherin ( CDH1 ) is a glycoprotein that mediates adhesion between epithelial cells and also suppresses cancer invasion. Mutation or deletion of the CDH1 gene has been reported in 30–60% cases of invasive lobular carcinoma (ILC). However, little is known about genomic differences between ILC with and without a CDH1 alteration. Therefore, we analyzed whole genome sequencing data of 169 ILC cases from The Cancer Genome Atlas (TCGA) to address this deficiency. Our study shows that CDH1 gene was altered in 59.2% (100/169) of ILC. No significant difference was identified between CDH1 -altered and -unaltered ILC cases for any of the examined demographic, clinical or pathologic characteristics, including histologic grade, tumor stage, lymph node metastases, or ER/PR/HER2 states. Seven recurrent mutations ( PTEN , MUC16 , ERBB2 , FAT4 , PCDHGA2 , HERC1 and FLNC ) and four chromosomal changes with recurrent copy number variation (CNV) (11q13, 17q12-21, 8p11 and 8q11) were found in ILC, which correlated with a positive or negative CDH1 alteration status, respectively. The prevalence of the most common breast cancer driver abnormalities including TP53 and PIK3CA mutations and MYC and ERBB2 amplifications showed no difference between the two groups. However, CDH1 -altered ILC with an ERBB2 mutation shows a significantly worse prognosis compared to its counterparts without such a mutation. Our study suggests that CDH1 -altered ILC patients with ERBB2 mutations may represent an actionable group of patients who could benefit from targeted breast cancer therapy.

The correlation of serum and synovial fluid (SF) pituitary adenylate cyclase-activating polypeptide (PACAP) levels with disease progression of primary knee osteoarthritis (OA) was explored. Radiographic severity of OA was determined by Kellgren–Lawrence (K-L) grades. PACAP levels were measured by ELISA before treatment, and 4 and 8 wk following hyaluronic acid (HA) injection. Levels of IL-1β and MMP-3 were also detected. The numeric pain scale (NPS), revised Oxford Knee Score (OKS), and American Knee Society Score (AKSS) were employed to evaluate to symptomatic severity. Receiver-operating-characteristic (ROC) curve analysis was carried out to compare the diagnostic value of PACAP, IL-1β, and MMP-3 for the K-L grade. PACAP concentrations in SF but not serum were significantly lower in OA patients compared with controls. SF PACAP levels were negatively associated with K-L grades and higher NPS as well as worse AKSS and OKS. Further analysis demonstrated that PACAP concentration in SF was negatively correlated with expressions of IL-1β as well as MMP-3 and may act as a marker for radiographic progression along with MMP-3. Last, we found SF PACAP levels exhibited an incremental trend after HA injection. These findings confirmed the crucial role of PACAP deficiency in the development of primary knee OA.

PURPOSE This study aimed to explore the effect of extended-release paliperidone (paliperidone ER) and olanzapine on heart rate variability (HRV) in patients with schizophrenia. METHODS A total of 106 patients with schizophrenia diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) were randomly divided into the paliperidone ER group or the olanzapine group for an 8-week clinical trial, with 53 patients in each group. The time domain and frequency domain analyses including the SD of all the R-R intervals in 24 hours (SDNN), the SD of the mean value of all the normal R-R intervals in every 5-minute interval within 24 hours (SDANN index), the mean value of the SD of all the normal R-R intervals in every 5-minute interval within 24 hours (SDNN index), the root mean square of successive R-R differences, the percentage of adjacent R-R intervals that differ by more than 50 milliseconds, high-frequency power (HF), low-frequency power (LF), and LF/HF were adopted to assess the HRV of patients at baseline and after treatment for 8 weeks in each group. The Positive and Negative Symptom Scale was used to evaluate the clinical efficacy. The incidence rates of adverse reactions were also calculated. RESULTS In total, 48 patients in the paliperidone ER group and 45 patients in the olanzapine group completed the entire 8-week treatment. The SDNN, SDNN index, and SDANN index in the olanzapine group were significantly lower than those in the paliperidone ER group (P < 0.05) after treatment for 8 weeks, whereas their mean LF level was higher than that in the paliperidone ER group (P < 0.05) after completion of treatment. Patients in the olanzapine group showed a significant decrease in the SDNN, SDANN index, and SDNN index as well as a statistical increase in the LF and LF/HF in comparison with the pretreatment values (P < 0.05), whereas patients in the paliperidone ER group showed a decrease in the SDANN index and a statistical increase in the LF in comparison with the pretreatment values (P < 0.05). CONCLUSION The HRV of patients with schizophrenia changes when they are administered with paliperidone ER or olanzapine, and more attention should be paid to their cardiac autonomic function when using these 2 antipsychotics.

Background: Diabetes is associated with an increased risk of heart failure, cardiac arrhythmias and sudden cardiac death. We previously showed that ROCK2 expression is elevated in diabetic rat hearts, and that ROCK inhibition acutely improves their contractile function. In the present study we investigated whether inhibition of ROCK or partial deletion of ROCK2 improves impaired Ca handling in the diabetic heart. Methods: Contractile properties and Ca transients were measured before and after treatment with the ROCK inhibitor Y-27632 (1 μM) in fluo-4-loaded cardiomyocytes isolated from streptozotocin (STZ)-diabetic or non-diabetic rats. Cardiac function was determined in vivo, and contractile properties and Ca transients also measured in cardiomyocytes from non-diabetic and STZ-diabetic wild-type (WT) and ROCK2+/− mice. Results: ROCK inhibition improved some parameters of contractile function and Ca handling in cardiomyocytes from diabetic rat hearts. In addition, ROCK inhibition attenuated the diabetes-induced delayed aftercontractions (DACs) and associated irregular Ca transients induced by increased [Ca]o. Although no overt cardiac dysfunction was detected in diabetic WT mice, cardiomyocytes from these mice also developed arrhythmic Ca transients in response to increased [Ca]. These were attenuated in cardiomyocytes from diabetic ROCK2+/− mice, in association with decreased diastolic Ca leak and with reduction of the diabetes-induced increased phosphorylation of both CaMKII and the ryanodine receptor (RyR). Conclusions: These data suggest that ROCK2 contributes to diabetes-induced impaired cardiac Ca homeostasis, at least in part by promoting CaMKII-mediated phosphorylation of RyR. This may have important clinical implications for the treatment of the increased incidence of dysrhythmias in diabetes., This study was supported by operating grants from the Canadian Institutes of Health Research (MOP 97861) and Diabetes Canada (KMM), and Spanish Ministry of Economy and Competitiveness SAF2014-58286-C2-1R (LHM).

Background It has been demonstrated that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic knee osteoarthritis (PTKOA).Pituitary adenylate cyclase-activating polypeptide (PACAP), a common neuropeptide exerting a wide spectrum of functions, has been proved to inhibit inflammation and prevent cartilage degeneration. Objective The current study was performed to investigate circulating and synovial fluid PACAP concentrations in ACL injury patients to determine their relationship with the disease progression of the severity of post-traumatic knee osteoarthritis (PTKOA). Methods 72 ACL injury patients receiving arthroscopical examination and surgery were enrolled in the study. Meanwhile, 60 gender-and-age non-traumatic patellar dislocation patients were enrolled as controls. The VAS score, Lysholm Score and International Knee Documentation Committee (IKDC) score were all recorded to evaluate the clinical severity. Serum and synovial fluid (SF) PACAP levels were investigated by enzyme-linked immunosorbent assay (ELISA).The IL-1β and TNF-α levels were also investigated. The degree of meniscus injury was assessed by MR imaging. The modified Mankin score was recorded to examine the cartilage histopathological alternations. Receiver operating characteristic (ROC) curve was performed to discuss the diagnostic value of PACAP levels for the prediction of the radiographic grading in comparison with IL-1β and TNF-α. Results Serum PACAP levels between PTKOA patients and patellar dislocation did not reach significant differences. However, SF PACAP levels were significantly lower in PTKOA patients than controls. In addition, SF PACAP levels were negatively associated with MRI imaging grade for meniscus injury and VAS score, and were positively associated with Lysholm and IKDC scores. In addition, SF PACAP levels were negatively related to Mankin score as well as the expressions of IL-1β and TNF-α. ROC analysis curve showed that attenuated PACAP may serve as a favorable marker for the diagnosis of MRI for meniscus injury. Conclusions SF PACAP concentrations showed an independent and negative association with disease severity in PTKOA following ACL injury. Local treatment with PACAP may act as a possible adjuvant therapy for delaying the process of PTKOA.

SummaryPathogens-induced platelet activation contributes to inflammation in cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced inflammation and potential mechanisms involved. As expected, we show that SSL5 activates human platelets and induces generation of platelet microparticles (PMPs). Flow cytometry and scanning electron microscopy studies demonstrate that SSL5-induced PMPs (SSL5-PMPs) bind to monocytes, causing aggregate formation. In addition, SSL5-PMPs provoke monocyte expression and release of inflammatory mediators, including interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. SSL5-PMPs also enhance MCP-1-induced monocyte migration. Blockade of CD40 and CD40 ligand (CD40L) interactions with neutralising antibodies significantly reduce monocyte release of inflammatory mediators and migration induced by SSL5-PMPs. SiRNA-mediated silencing of CD40 or TNF receptor (TNFR)-associated factor 6 (TRAF6) gene largely abrogates phosphorylation and nuclear translocation of NFkB (p65). In conclusion, SSL5 provokes the release of inflammatory mediators in monocytes, at least in part, via PMPs-mediated activation of the CD40/TRAF6/NFkB signalling pathway, though it normally inhibits leukocyte function. Our findings thus reveal a novel mechanism by which S. aureus induces inflammation.

Previous studies have indicated that complex interactions among viral, environmental and genetic factors lead to hepatocellular carcinoma (HCC). To identify susceptibility alleles for hepatitis B virus (HBV)-related HCC, the present study conducted a pilot two-phase genome-wide association study (GWAS) in 660 Han Chinese individuals. In phase 1, a total of 500,447 single-nucleotide polymorphisms (SNPs) were genotyped in 50 HCC cases and 50 controls using Affymetrix GeneChip 500k Array Set. In phase 2, 1,152 SNPs were selected from phase 1 and genotyped in 282 cases and 278 controls using the Illumina GoldenGate platform. The prior probability of HCC in control subjects was assigned at 0.01, and false-positive report probability (FPRP) was utilized to evaluate the statistical significance. In phase 1, one SNP (rs2212522) showed a significant association with HCC (Pallele=5.23×10−8; ORallele=4.96; 95% CI, 2.72–9.03). In phase 2, among 27 SNPs with unadjusted Pallele

Objective This study explores the unmet psychosocial rehabilitation needs of cancer survivors. Methods Sixty-eight cancer survivors from the Shanghai Cancer Rehabilitation Club in China participated in one of the eight focus groups. These were transcribed verbatim, coded using thematic analysis and analysed using NVivo 10. Results Five main themes were identified: the need for (1) better information: Chinese cancer survivors find it difficult to sort and evaluate the overwhelming mass of information with which they are confronted; (2) psychological support: survivors fear cancer relapse and neighbours' discrimination against them; support from other cancer survivors can relieve the stress; (3) support for survivors' families: like the survivors, family members are under great but usually unacknowledged pressure; (4) improved health and medical services: community health service centres provide little medical, informational or psychological support for cancer survivors, who seek and expect more communication with doctors; and (5) assistance with the financial burden: costs of treatment and lack of adequate medical insurance cause substantial financial pressure for survivors. Conclusions This study shows that, in addition to their illness, Chinese cancer survivors experience a range of stresses related to their financial circumstances, lack of reliable and summarised information, poor access to support and services (including for their families) and discrimination. Support from families seems to improve survivors' ability to cope. Cancer survivors (and their families) need an integrated package of support from their families, doctors and other service providers, hospitals and communities. These findings can inform approaches to continuing care for cancer survivors. Copyright © 2015 John Wiley & Sons, Ltd.

We have read Char's comment1. Thanks for readers’ attention and valuable feedback on our article. Following was our response to Char's question about data overlap.Firstly, the meta‐analysis reprocessed the existing data about COVID‐19 patients in published articles, and involved no other information outside of the article.This article is protected by copyright. All rights reserved.