Secondly, we provide an overview of studies reporting the prevalence of vitamin D deficiency in traumatology and diverse orthopaedic diseases including bone oncology. Lastly, we emphasise recent findings and touch on future perspectives in vitamin D research.

Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain.

We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasivdities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation.

A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

Osteoarthritis (OA) is characterized by erosion and degradation of articular cartilage. This study assessed the effects of curcumin on mouse knee cartilage chondrocytes.

Chondrocytes were treated for 24 hours with interleukin IL-1β (10 ng/mL) alone, or the combination of curcumin (10, 20, and 50 µM) and IL-1β. The proliferation, viability, and cytotoxicity of the chondrocytes were evaluated by the MTS assay. Expression of SOX9, AGG, Col2α, MMP9, ADAMTS5, COX2, iNOS, pIκB-α, pNF-κB, and hypoxia-inducible factor-2α (HIF-2α) were detected by western blotting or quantitative polymerase chain reaction (q-PCR). Nuclear translocation of NF-κB and HIF-2α were investigated by immunofluorescence and immunohistochemistry. In

experiments, mice were subjected to destabilization of the medial meniscus (DMM) and given curcumin orally for 6 weeks. Cartilage integrity was evaluated by OARSI (Osteoarthritic Research Society International) scores.

Curcumin significantly inhibited the IL-1β-induced reduction of cell viability, degradation of ECM, and the expression of SOX9, Col2α, and AGG (P<0.01). Western blotting, immunofluorescence and immunohistochemistry experiments demonstrated that curcumin dramatically inhibited the activation of NF-κB/HIF-2α in chondrocytes treated with IL-1β (P<0.01). The articular scores were significantly lower in the DMM-induced OA mice compared to OA mice treated with curcumin (P<0.01).

Curcumin may have the potential to inhibit OA development, partly through suppressing the activation of the NF-κB/HIF-2α pathway.

Curcumin may have the potential to inhibit OA development, partly through suppressing the activation of the NF-κB/HIF-2α pathway.

Acute myeloid leukemia (AML) is a common and lethal hematopoietic malignancy that is highly dependent on the immune microenvironment. However, light has yet to be shed on the landscape of adaptive immunity-related genes. This work aimed to uncover the novel molecular events in AML and potential therapeutic strategies for AML treatment.

For the current research, the transcriptional information of 732 genes that participate in adaptive immunity was collected from 173 patients with AML, and the patients were grouped into different cohorts based on the different expression patterns. The correlations between gene expression and clinical characteristics, including prognosis, were studied.

According to the notably different expressions of adaptive immunity-related genes, the 173 patients were divided into 2 clusters and 3 subclusters. No significant differences in overall survival (OS) or progression-free survival (PFS) were detected between the clusters or subclusters. There were obvious discrepancies found iely correlated with prognosis, thus revealing a potential therapeutic target for AML.

This study has uncovered the expression profile of adaptive immunity-related genes in AML. The different gene expression patterns are not associated with survival, but are significantly correlated the FAB types. CLEC2B expression is low in patients with M2 type and is negatively correlated with prognosis, thus revealing a potential therapeutic target for AML.

Idiopathic epiretinal membranes (ERMs) often cause metamorphopsia and the progressive loss of central visual function, which seriously affect quality of life. We aimed to map the distribution pattern of idiopathic ERMs in China and to examine the factors affecting the surgical choices of multicenter surgeons.

A national ophthalmologist-oriented questionnaire was administered, applied with a multistage probability sampling method. Data of essential characteristics, including age, professional title, residence, and perioperative and postoperative care, were gathered. All the data are expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The histogram and choropleth map were generated by Excel 2016.

In total, 1,137 (85.2%) valid responses were returned with maximized response and completion rates. The study showed that monthly admission numbers, and preoperative and postoperative care varied significantly across different regions in China. Generally, the monthly patient admission numbers were lower in the Western region than the Eastern region. However, patients in the Eastern region had longer preoperative waiting periods and shorter hospital stays.

The epidemiology of idiopathic ERMs varied significantly across different regions in China. The distribution pattern of ERM in China and the overview of the factors affecting the surgery approaches of multicenter surgeons were shown. The findings of this study will contribute to the formulation of medical policies, and provide insights into the healthcare environments across China.

The epidemiology of idiopathic ERMs varied significantly across different regions in China. The distribution pattern of ERM in China and the overview of the factors affecting the surgery approaches of multicenter surgeons were shown. The findings of this study will contribute to the formulation of medical policies, and provide insights into the healthcare environments across China.

Leptomeningeal metastasis (LM) is a catastrophic complication for patients with non-small cell lung cancer (NSCLC) and carries an extremely poor prognosis. The efficacy of osimertinib 80 mg once daily for epidermal growth factor receptor-mutated (

) NSCLC with LM has yet to be fully assessed. This study aimed to investigate the efficacy of osimertinib in such patients and their genetic profiles at the time of LM diagnosis.

From January 2016 to April 2020, pretreated

NSCLC patients who had progressed with cytologically confirmed symptomatic LM and received osimertinib 80 mg once daily were enrolled retrospectively. The objective response rate (ORR) and disease control rate (DCR) were evaluated, along with progression-free survival (PFS) and overall survival (OS). Next-generation sequencing of paired samples of cerebrospinal fluid and plasma collected at LM diagnosis was performed simultaneously.

Forty cases of

lung adenocarcinoma with LM were analyzed. Females accounted for 75.0% of enrollees. Of simertinib 80 mg once daily shows good efficacy in pretreated

NSCLC patients with LM regardless of their T790M status. Combining cerebrospinal fluid and plasma testing can aid in revealing more genetic information.

Osimertinib 80 mg once daily shows good efficacy in pretreated EGFRm NSCLC patients with LM regardless of their T790M status. Combining cerebrospinal fluid and plasma testing can aid in revealing more genetic information.

Ceftobiprole is a novel β-lactam cephalosporin with activity against Gram-positive and -negative bacteria. The aim of the present study was to investigate the pharmacokinetics (PK), pharmacokinetics/pharmacodynamics (PK/PD), safety and tolerance of ceftobiprole in Chinese participants, to evaluate this dosage regimen for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in China.

The use of ceftobiprole was investigated in a single-center, open-label, single- and multiple-dose study using 12 healthy Chinese participants (6 males and 6 females). Ceftobiprole plasma and urine concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. The PK/PD characteristics of 500 mg ceftobiprole every 8 h at 1.5-, 2-, 3-, or 4-h infusion time were analyzed by Monte Carlo simulations (MCS).

The maximum plasma concentration of ceftobiprole was observed 2 h after dosage; its terminal half-life was about 3 h. Ceftobiprole was predominantly eliminated in urine, and the cumulative excretion in 24 h was >90%. There was no accumulation after multiple dosing. Both single and multiple doses were well tolerated, with no severe or serious adverse events (AEs). PK/PD analysis indicated that

(

) and

(

) were sensitive to ceftobiprole. About half of extended-spectrum β-lactamase (ESBL) non-producing

are sensitive to ceftobiprole, according to PK/PD results of ceftobiprole. For

(

), no regimen was found to be effective against strains.

The PK/PD results indicated that 500 mg ceftobiprole every 8 h at 2-h infusion time is expected to achieve good microbiological efficacy in the treatment of CAP and HAP in China.

The PK/PD results indicated that 500 mg ceftobiprole every 8 h at 2-h infusion time is expected to achieve good microbiological efficacy in the treatment of CAP and HAP in China.

Coronary artery disease, fatty liver disease, cardiac abnormalities, the metabolic syndrome, and insulin resistance may all occur in association with an increase of epicardial adipose tissue volume (EATV). Previous studies have shown that some cardiovascular-risk factors and healthy behaviors were related to a lower risk of EATV increase. The main purpose of this study was to determine whether ideal cardiovascular health (CVH) metrics were correlated with the prevalence of high EATV.

The study commenced across 2013 and 2014 and involved volunteers from the Jidong (East Hebei) district. A cohort of 2,482 participants aged 45 years or older were randomly selected, of which 49.9% were women and none were diagnosed as having cancer, stroke, or heart diseases such as atrial fibrillation, heart failure, or myocardial infarction. The study collected information concerning seven CVH metrics; namely body mass index, dietary intake, smoking, blood pressure, physical activity, total cholesterol, and fasting blood glulation is negatively correlated with the prevalence of high EATV, supporting the greater use of EATV as a useful parameter in clinical practice.

Segmentation of coronavirus disease 2019 (COVID-19) lesions is a difficult task due to high uncertainty in the shape, size and location of the lesions. CT scan image is an important means of diagnosing COVID-19, but it requires doctors to observe a large number of scan images repeatedly to determine the patient’s condition. Moreover, the low contrast of CT scan and the presence of tissues such as blood vessels in the background increase the difficulty of diagnosis. To solve this problem, we proposed an improved segmentation model called the residual attention U-shaped network (ResAU-Net).

A novel method to detect and segment coronavirus pneumonia was established based on the deep-learning algorithm. Firstly, the CT scan image was input, and lung segmentation was then realized by U-net. Then, the region of interest was selected by the minimum circumscribed rectangle clipping method. Finally, the proposed ResAU-Net, which includes attention module (AMB), residual module (RBM) and sub-pixel convolution moduliency of pneumonia.

Obesity is a growing global public health problem. It has been associated with diabetes, cardiovascular disease, cancer, and an increased risk of all-cause mortality, as well as infertility. Calorie restriction (CR) is an effective life intervention to defend against obesity. This study aimed to investigate the effects of long-term moderate CR on the reproductive function and underlying mechanisms in a mouse model of obesity.

Male C57BL/6 mice were randomized to two groups receiving either a standard diet (STD) or a high-fat diet (HFD) for 8 weeks to induce obesity. The HFD-induced obesity mice were further randomized into two groups HFD group and CR group (reduced the mean amount of HFD by 25%). After 12 weeks, the body weight, testicular coefficients, fasting blood glucose (FBG), serum triglyceride (TG), and total cholesterol (TC) were detected and measured. The sperm quality was detected by an automatic sperm quality analyzer (SQA-V). The structure of testicular tissues was examined by hematoxylin and eosin (HE) staining. Testicular cell apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The levels of NAD-dependent deacetylase sirtuin-1 (SIRT1) and antioxidative enzymes were detected in the testes.

CR treatment reduced weight gain and increased testicle coefficients in HFD-induced obese mice. CR reduced the serum level of FBG, TG, and TC, and increased the serum levels of testosterone. Moreover, CR increased sperm count and motility, and sperm normality in obese mice. Furthermore, CR ameliorated the testicular morphological damage and cell apoptosis in obese mice. CR also attenuated the oxidative stress level and increased the protein expressions of SIRT1 in testicular tissues of obese mice.

Long-term moderate CR improves obese male fertility, probably by alleviating oxidative stress via activation of SIRT1 signaling.

Long-term moderate CR improves obese male fertility, probably by alleviating oxidative stress via activation of SIRT1 signaling.

Liver fibrosis is a common result of the repair process of various chronic liver diseases. This study is a network pharmacology study on the potential therapeutic targets and biological mechanisms of Centella asiatica for liver fibrosis.

The chemical components and potential targets of Centella asiatica were screened through TCMSP, PubChem database, and Swiss Target Prediction database. The DisGeNET and GeneCards databases were used to obtain targets of HF. Venn diagrams were used to find key targets, and draw protein interaction maps. Cytoscape software was used to construct an interaction network map of drug-component-target-disease-pathway. The mechanisms of action were predicted through enrichment analysis and KEGG analysis.

In total, 6 main components, 297 drug targets, 337 HF targets, and 48 drug-disease targets were obtained in Centella asiatica. The key targets involved IL6, TNF, VEGFA, TP53, IL1β, MMP9, CXCL8, EGFR, JUN, SRC, MMP2, and TGF-β, among others. A total of 1293 entries were obtained by Gene Ontology (GO) enrichment analysis, which mainly involved the regulation of reactive oxygen species metabolic process, the regulation of smooth muscle cells, and the regulation of DNA-binding transcription factor activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment mainly screened 191 pathways, including the MAPK signaling pathway, the relaxin signaling pathway, and the Toll-like receptor signaling pathway, among others.

Centella asiatica may have a therapeutic effect on HF through multiple targets and pathways. Its mechanism is mainly related to the MAPK signaling pathway and the relaxin signaling pathway.

Centella asiatica may have a therapeutic effect on HF through multiple targets and pathways. Its mechanism is mainly related to the MAPK signaling pathway and the relaxin signaling pathway.

Stem cell transplantation has been increasingly used for spinal cord repair, and some achievements have been made. However, limited stem cell sources as well as immune rejection and ethical issues have restricted its wide application. Therefore, to achieve further breakthroughs regarding the application of stem cell transplantation to treat spinal cord injury (SCI), it is important to develop a stem cell line that can effectively avoid immune rejection and ethical issues.

Urine cells (UCs) were induced to differentiate into induced pluripotent stem cells (iPSCs), which then further differentiated into neural stem cells (NSCs). Relevant tests were performed, and three-dimensional (3D) printed scaffolds were prepared. Thirty C57BL/6 mice were divided into 5 groups based on a random number table a sham group, an SCI group, an SCI + control group, an SCI + siNC group, and an SCI + siGAS5 group (n=6). The latter 4 groups replicated SCI models. Mice in the SCI + control group were transplanted with 3D scaffoldsicantly increased the expression level of B cell lymphoma/leukemia-2 (Bcl-2) (P<0.01) but decreased the expression levels of Bcl-2 associated X protein, cytochrome C, and cleaved caspase-3 (P<0.001).

The overexpression of lncRNA-GAS5 can promote spinal cord repair and inhibit neural apoptosis via the transplantation of 3D printed scaffolds loaded with iPSd-NSCs.

The overexpression of lncRNA-GAS5 can promote spinal cord repair and inhibit neural apoptosis via the transplantation of 3D printed scaffolds loaded with iPSd-NSCs.

To explore the effectiveness of adenovirus-enhanced green fluorescent protein-vascular endothelial growth factor165 (AD-EGFP-VEGF165) transfection on fibroblasts from mice, and we assessed whether VEGF165 restores the angiogenesis of oral submucous fibrosis (OSF) in mice.

AD-EGFP-VEGF165 and AD-EGFP were transfected into fibroblasts from mouse buccal tissues in vitro. The expression of VEGF before and after transfection was detected by RT-qPCR and ELISA in each group of fibroblasts. Fifteen OSF mice (pre-experimental construction) were randomly divided into 3 groups, and equal amounts of AD-EGFP-VEGF165 virus, AD-EGFP virus, and saline were injected into the buccal submucosal tissue of OSF mice. The expression of VEGF and local tissue angiogenesis were observed and measured in each group of animals.

The Ad-EGFP-VEGF165-transfected fibroblasts increased human and mouse VEGF expression compared to the Ad-EGFP group and control group (P<0.05). The buccal submucosal tissue of mice was injected with Ad-EGFP-VEGF165 after the 6th day, and the expression of VEGF was effectively expressed in AD-EGFP-VEGF165 group (P<0.05), while no positive expression observed in other groups. and the number of microvessels in the AD-EGFP-VEGF165 group increased significantly compared to the other groups (P<0.05).

Ad-EGFP-VEGF165 can be successfully transfected into fibroblasts from mice, and restored the angiogenesis of OSF in mice.

Ad-EGFP-VEGF165 can be successfully transfected into fibroblasts from mice, and restored the angiogenesis of OSF in mice.

This study investigated the clinical efficacy of different mass concentrations of pingyangmycin in the local injection treatment of lip venous malformation. An animal experimental study of the histopathological effects of different mass concentrations of pingyangmycin on the normal lip tissue of rabbits was also conducted.

(I) We retrospectively analysed 98 out-patients with lip venous malformation in the Stomatological Hospital and the Fourth Affiliated Hospital of China Medical University from January 2008 to June 2013. The 98 cases were treated by local injection of different mass concentrations (8 mg/3 mL and 8 mg/5 mL) of pingyangmycin for the different sites of the lips. The clinical efficacy was observed, and adverse reactions were recorded. (II) 60 healthy male rabbits were randomly divided into three groups a 8 mg/5 mL pingyangmycin group, a 8 mg/3 mL pingyangmycin group, and a control group. The right upper lips of the experimental groups were injected with 1ml pingyangmycin (8 mg/5 mL) and 1ml ould be paid when the concentration is 8 mg/3 mL to avoid local tissue atrophy and other complications.

The local injection of pingyangmycin in the treatment of lip venous malformations was efficient, safe and reliable. In the process of clinical application, attention should be paid when the concentration is 8 mg/3 mL to avoid local tissue atrophy and other complications.

Using fMRI to analysis of brain function state in migraineurs at different phases, and combined with the clinical symptoms to explore the mechanisms and outcomes of migraine.

It’s a case-control study. We analyzed the resting-state brain functional magnetic resonance imaging in 19 patients with episodes, 22 patients with interictal phase, and 22 healthy controls. The ReHo method was used for post-processing. All subjects were evaluated using the Montreal cognitive assessment (MoCA) scale, simple mental state examination (MMSE), Hamilton anxiety (HAMA) scale, and Hamilton depression (HAMD) scale. The subjects’ clinical indicators (such as frequency of attack, course of disease, duration of each headache, and severity of headache) were correlated with the ReHo values of brain regions. This study was approved by the ethics committee of Yangtze River Shipping General Hospital.

Compared with the interictal, patients in the episode group had lower activation in bilateral anterior cingulate cortex (ACC), with e condition becomes chronic, and the remodeling of the brain.

We need to observe the course of migraine as a whole. In the interictal period, the cuneus and lingual gyrus may affect the development of the disease. The ACC regulates different states of migraine by inducing anti-injury sensation regulation function. The paracentric lobule is not only associated with migraine attacks, but also with the frequency. This may have an effect on the outcome of subsequent migraines, as well as whether the condition becomes chronic, and the remodeling of the brain.

This study sought to compare the surgical results of patients undergoing a laparoendoscopic single-site myomectomy (LESS-M) and a conventional laparoscopic myomectomy (CLM) at our hospital.

The basic data of 233 patients undergoing LESS-M and 233 patients undergoing CLM at the Obstetrics and Gynecology Hospital Affiliated to Fudan University were collected from January 2018 to January 2020, and the results of the operations were compared by evaluating a number of factors, including operation time, intraoperative bleeding, postoperative fever, and postoperative maximum body temperature.

The operation times of the LESS-M and CLM groups were 83.9±33.4 and 75.2±26.7 min, respectively; the difference between the groups was statistically significant. The surgical blood loss of the LESS-M group was 86.1±76.9 mL, and that of the CLM group was 83.8±79.9 mL (P>0.05). When the diameter of a fibroid was ≥8 cm, a fibroid was located in the posterior wall or the number of fibroids was ≥4, the operation time of the CLM group was shorter than that of the LESS-M group. When the diameter of a fibroid was ≥8 cm, the blood loss of the CLM group was less than that of the LESS-M group.

LESS-M is safe and feasible. If the diameter of a fibroid is ≥8 cm, the fibroid is located in the posterior wall, or the number of fibroids is ≥4, the utility of single-port surgery should be carefully considered.

LESS-M is safe and feasible. If the diameter of a fibroid is ≥8 cm, the fibroid is located in the posterior wall, or the number of fibroids is ≥4, the utility of single-port surgery should be carefully considered.

To explore the source, the role and the specific mechanism of IL-35 and its downstream molecules in the development of pulmonary hypertension.

8-10 weeks male mice were undergoing hypoxia combined with SU5416 (HySu) to establish a pulmonary hypertension (PH) model. The phenotype of PH mice was measured by immunohistochemistry and immunofluorescence staining. The levels of two subunits (EBI3 and p35 subunits) in lung tissue were measured by real-time PCR and western blotting. EBI3 monoclonal antibody was administrated as IL-35 neutralization to offset systemic IL-35 expression. Fludarabine, an inhibitor of STAT1 (signal transducer and activator of transcription 1) was used to clarify the role of STAT1 under IL-35 treatment.

After pulmonary hypertension, the expression of IL-35 and its two subunits (EBI3 and p35 subunits) in lung tissue were significantly increased. And the two subunits of IL-35 are highly expressed in Treg cells. Compared with the controlled PH mice, the IL-35 neutralization PH mice showsels and alleviate the progression of pulmonary hypertension by reducing the proliferation of endothelial cells.

Brain glioblastoma multiforme (GBM) is the most common primary malignant intracranial tumor. The prognosis of this disease is extremely poor. While the introduction of β-interferon (IFN-β) regimen in the treatment of gliomas has significantly improved the outcome of patients; The mechanism by which IFN-β induces increased TMZ sensitivity has not been described. Therefore, the main objective of the study was to elucidate the molecular mechanisms responsible for the beneficial effect of IFNβ in GBM.

Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) GBM and GSE83300 dataset from the Gene Expression Omnibus. Univariate Cox regression analysis and lasso Cox regression model established a novel 4-gene IFN-β signature (peroxiredoxin 1, Sec61 subunit beta, X-ray repair cross-complementing 5, and Bcl-2-like protein 2) for GBM prognosis prediction. Further, GBM samples (n=50) and normal brain tissues (n=50) were then used for real-time polymerase chaits, which may help in clinical decision making for individual treatment.

In the present study, we established a novel IFN-β-associated gene signature to predict the overall survival of GBM patients, which may help in clinical decision making for individual treatment.

Emerging evidence suggests that inflammation induced by the inflammasome plays a crucial role in the course of Parkinson’s disease (PD). Ulinastatin (UTI) has shown significant anti-inflammatory effects. However, few studies have examined whether UTI protects neurons through its anti-inflammatory effects in PD. The purpose of this study is to determine whether UTI exerts neuroprotection in a PD cell model and to explore the mechanisms.

SH-SY5Y cells and nerve growth factor (NGF)-treated PC12 cells were used to establish MPP

induced PD cell models. Cells were pre-treated with UTI, then cell viabilities were detected using the MTT assay. Lactate dehydrogenase (LDH) release was detected using the LDH release assay kit. Inflammatory factors such as IL-1β, IL-6, and TNF-α were detected using ELISA. The expression levels of TH, NLRP3, caspase-1, ASC, IL-1β, and IL-18 were measured using western blotting, and DA release was detected using HPLC. A NLRP3 activator Nigericin was used to verify the effect of NLRP3 in the neuroprotective mechanism of UTI.

We observed decreased cell viability, increased apoptosis, and increased inflammatory factors such as IL-1β, IL-6, and TNF-α in the MPP

induced PD model. We also found decreased DA secretion and TH expression, as well as increased NLRP3, caspase-1, ASC, IL-1α, and IL-18 expression in the MPP

induced PD model. These changes were significantly attenuated by UTI pre-treatment in a dose dependent manner. NLRP3 activator Nigericin markedly increased LDH release, accelerated apoptosis, increased inflammation levels and decreased DA secretion and TH expression, suggesting that Nigericin eliminated the neuroprotective effect of UTI on MPP

treated cells.

Our data demonstrated that UTI pre-treatment performed a neuroprotective role in the MPP

induced PD cell models by inhibiting the NLRP3 pathway.

Our data demonstrated that UTI pre-treatment performed a neuroprotective role in the MPP+ induced PD cell models by inhibiting the NLRP3 pathway.

Anti-hypertensive drugs are widely used to control blood pressure, yet their effects on haemodynamics, especially in Chinese populations, and the potential for non-invasive methods to monitor these changes, are poorly understood. This study aimed to determine the early and late effects of bisoprolol treatment on blood pressure, cardiac output (CO), stroke volume (SV), heart rate (HR), systematic vascular resistance (SVR), and inotropy measured in Chinese patients with hypertension.

Twelve Chinese subjects (median age 55 years, interquartile range 52-58 years; 33% male) with uncontrolled hypertension were recruited at the Prince of Wales Hospital in Hong Kong and haemodynamic measurements were assessed using a non-invasive Ultrasonic Cardiac Output Monitor (USCOM). Seven hourly measurements were taken before and after bisoprolol 2.5 mg on day 1 (T0 to T6), and in nine patients this was repeated six weeks later (TF0 to TF6). Any BP change of 5 mmHg was considered clinically significant and P<0.05 was conc changes between 6 hours of the first dose and the dose after 6 weeks of bisoprolol treatment are similar. Long-term therapy can effectively reduce blood pressure by reducing SVR.

Detection of genomic rearrangements, like anaplastic lymphoma kinase (

) fusions, is a pivotal requirement in non-small cell lung cancer (NSCLC) for the initiation of a targeted treatment. While tissue testing remains the gold standard, detection of these alterations using liquid biopsies is an unmet need. To enable the detection of

rearrangements from circulating-free RNA (cfRNA) from NSCLC patients, we have evaluated a novel reverse transcription PCR (RT-PCR) based assay.

Sixty-six patients with advanced stage NSCLC were included in the study. ALK status was determined by immunohistochemistry (IHC) and/or FISH on tissue sections. For the detection of

rearrangements from 2ml plasma collected in EDTA or Streck BCT DNA tubes, cfRNA was extracted using a prototype cfRNA sample preparation method and tested by a novel multiplex ALK/RET RT-PCR assay (Roche).

Of the forty-two patients with an

rearrangement, 30 (71%) were included at baseline. In 10 of the baseline patients, an

rearrangement was detected by RT-PCR [baseline sensitivity 33.33% (95% CI 17.29-52.81%)]. All 24 negative ALK IHC/FISH-negative patients were negative using the RT-PCR based assay (specificity =100%).

The prototype Roche ALK/RET RT-PCR assay was able to detect

fusion transcripts in the plasma of NSCLC patients at baseline as well as at disease progression with limited sensitivity but high specificity. Consequently, this assay could potentially be considered to select patients for an ALK-targeting therapy when tissue samples are lacking.

The prototype Roche ALK/RET RT-PCR assay was able to detect ALK fusion transcripts in the plasma of NSCLC patients at baseline as well as at disease progression with limited sensitivity but high specificity. Consequently, this assay could potentially be considered to select patients for an ALK-targeting therapy when tissue samples are lacking.

Management of large numbers of reverse transcriptase-polymerase chain reactions (RT-PCR) for diagnosis of coronavirus 2019 disease (COVID-19) requires robust infrastructures, located in dedicated premises with a high standard of biosafety procedures, and well-trained personnel. The handling of a „run-of-river sample” to obtain rapid reporting of results is challenging.

We studied the clinical performance of the Idylla™ SARS-CoV-2 Test (index test) on a platform capable of fully automated nucleic acid testing including extraction, amplification, and detection in a single-use cartridge to establish the diagnosis of COVID-19. The study was conducted on a prospective cohort of 112 volunteers with recent symptoms and an unknown SARS-CoV-2 status who came to free screening centers of the Nice metropolitan area. All subjects underwent bilateral nasopharyngeal sampling. One sample was processed using the index test, the other using the standard of care RT-PCR. Samples were treated blind.

Most of the participants (70%) were sampled within 4 days of symptom onset. Forty-five (40.2%) were positive for COVID-19. No clinical symptoms were distinguished between SARS-CoV-2 RT-PCR positive and negative subjects except anosmia and dysgeusia. Positive and negative agreement between the index and the standard of care test was 100%.

The Idylla™ SARS-CoV-2 Test is very sensitive, specific, rapid and easy to use in a near-patient RT-PCR approach to distinguish between symptomatic SARS-CoV-2 positive and negative patients in selected settings.

The Idylla™ SARS-CoV-2 Test is very sensitive, specific, rapid and easy to use in a near-patient RT-PCR approach to distinguish between symptomatic SARS-CoV-2 positive and negative patients in selected settings.

Seawater drowning is the major cause of accidental injury and death. The current treatment could not essentially block the source of the damage due to the complex etiology. Therefore, it is urgent to clarify the detailed mechanisms and find effective therapeutic approaches.

We performed

experiments to evaluate the damage of seawater drowning to lung epithelial cells. FACS, immunofluorescent staining, and western blot were used to detect the apoptosis. CCK-8 assay, Ki67 staining, and cell cycle analysis were used to assess the proliferation. The cytokine expression was determined by qRT-PCR and ELISA. Western blot and reporter assay were used for regulation mechanism study. For neutrophils development, Transwell assay and FACS were used for further investigation. Besides,

study was performed with the seawater drowning model in rats.

In this study, we found that seawater drowning induced mitochondria damage, which further accelerated epithelial cell apoptosis and repressed cell proliferation. Adminiegies.

Our study revealed the dual effect of ghrelin on seawater drowning induced lung injury via damage protection and immune repression, providing new insights into drowning injury pathogenesis and therapeutic strategies.

The 8

edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC 8

) has been launched with modifications in T staging. The University of Hong Kong liver cancer staging system (HKUSS) has been proven to better categorize hepatocellular carcinoma (HCC) into different T stages. This study aimed to compare the two systems’ predictive ability for HCC recurrence after primary surgical resection.

Patients who had primary, curative resection for HCC between 1989 and 2017 were reviewed. The Kaplan-Meier plot was used to estimate disease-free survival (DFS), and the log-rank test was used for survival comparison between subgroups. The two systems’ prediction of recurrence was evaluated by the Cox regression model.

Totally 1,815 patients were included. With AJCC 8

, the 5-year DFS was 58.9% for T1a, 52.3% for T1b, 30% for T2, 16.9% for T3, and 14.4% for T4. No survival difference was demonstrated between T1a and T1b (P=0.668) or between T3 and T4 (P=0.562). With HKUSS, the 5-HCC.

The Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement has been updated in 2015. Many diagnostic test accuracy (DTA) studies have been published in medical laboratory journals, but their adherence to the updated STARD statement remains unknown.

We searched the PubMed database to verify studies published in 4 laboratory journals, including

,

,

, and

, in 2019. DTA studies were identified and their adherence to the STARD statement was assessed.

A total of 45 studies were included in this analysis. Overall, 18 out of 34 STARD items were reported. The items (adherence rate) of sample size estimation (4%), adverse events (9%), protocol (9%), registration (16%), missing value (22%), indeterminate results (18%), and cross-tabulation (22%) were the most frequently unreported items.

Adherence to the STARD statement in DTA articles published in laboratory medicine seems as yet unsatisfactory. Our study emphasizes the necessity to improve the reporting quality of DTA studies published in medical laboratory journals.

Adherence to the STARD statement in DTA articles published in laboratory medicine seems as yet unsatisfactory. Our study emphasizes the necessity to improve the reporting quality of DTA studies published in medical laboratory journals.

Cardiovascular disease is the leading cause of death worldwide. We assessed the association of baseline heart rate with cardiovascular events and mortality in hypertensive and normotensive populations using a prospective urban and rural epidemiology cohort study in China.

A total of 29,554 individuals were involved in our analysis, distributed equally between groups of normotensive and hypertensive. The primary outcomes were myocardial infarction, stroke, major cardiovascular diseases, and cardiovascular mortality. Cox frailty models were utilized to estimate hazard ratios for cardiovascular outcomes, and restricted cubic splines were used to explore the shape of the association between baseline heart rate and cardiovascular mortality.

During a total observational time of 230,813 person-years, 402 myocardial infarction events, 1,096 stroke events, 1,540 major cardiovascular events, and 356 cardiovascular deaths were documented. In adjusted analyses, normotensive subjects with baseline heart rate >82.5 beats per minute had a 3.30-fold greater risk of cardiovascular death and an increased 72% risk of myocardial infarction, compared with individuals whose baseline heart rate was 65.5-71 beats per minute. A similar trend was observed for cardiovascular mortality in the hypertensive population, but the association was attenuated. Multivariable-adjusted restricted cubic splines showed linear associations between baseline heart rate and cardiovascular mortality in two groups of people (all P<0.05 for linearity).

Elevated baseline heart rate is associated with an increased risk of cardiovascular mortality and myocardial infarction in the normotensive population. The association is attenuated for cardiovascular death in hypertensive patients.

Elevated baseline heart rate is associated with an increased risk of cardiovascular mortality and myocardial infarction in the normotensive population. The association is attenuated for cardiovascular death in hypertensive patients.The first differentiation event in mammalian embryos is the formation of the trophectoderm, which is the progenitor of the outer epithelial components of the placenta, and which supports the fetus during the intrauterine life. However, the epigenetic and paracrine controls at work in trophectoderm differentiation are still to be fully elucidated and the creation of dedicated in vitro models is desirable to increase our understanding. Here we propose a novel approach based on the epigenetic conversion of adult dermal fibroblasts into trophoblast-like cells. The method combines the use of epigenetic erasing with an ad hoc differentiation protocol. Dermal fibroblasts are erased with 5-azacytidine (5-aza-CR) that confers cells a transient high plasticity state. They are then readdressed toward the trophoblast (TR) phenotype, using MEF conditioned medium, supplemented with bone morphogenetic protein 4 (BMP4) and inhibitors of the Activin/Nodal and FGF2 signaling pathways in low O2 conditions. The method here described allows the generation of TR-like cells from easily accessible material, such as dermal fibroblasts, that are very simply propagated in vitro. Furthermore, the strategy proposed is free of genetic modifications that make cells prone to instability and transformation. The TR model obtained may also find useful application in order to better characterize embryo implantation mechanisms and developmental disorders based on TR defects.Some European countries have successfully implemented country-specific control programs (CPs) for infectious cattle diseases that are not regulated or are regulated only to a limited extent at the European Union (EU) level. Examples of such diseases include bovine viral diarrhea (BVD), infectious bovine rhinotracheitis (IBR), and Johne’s disease (JD). The CPs vary between countries in the design and quality of collected data as well as methods used to detect infection and estimate prevalence or probability of freedom from infection. Differences in disease status between countries and non-standardized approaches to assess freedom from infection pose a risk for countries with CPs for non-regulated diseases as infected animals may influence the progress of the disease control or eradication program. The implementation of output-based standards allows estimation and comparison of the probability of freedom for non-regulated cattle diseases in European countries. The aim of the current study was to assess the exis cattle diseases and will further assist in the development and implementation of output-based standards.The objective of this paper is to provide a comparative review of three active surveillance and control programmes in the Danish cattle sector to highlight important differences for decision makers to develop successful programmes. The focus is on differences in purpose, principles, design and instruments applied to achieve the goals stated for each programme for bovine viral diarrhoea (BVDV), paratuberculosis and Salmonella Dublin. The purposes of the programmes are to reduce economic consequences and improve animal welfare, and for S. Dublin also to prevent zoonotic risk, with varying importance as motivation for the programmes over time. The targets of the BVDV and S. Dublin programmes have been to eradicate the diseases from the Danish cattle population. This goal was successfully reached for BVDV in 2006 where the programme was changed to a surveillance programme after 12 years with an active control programme. The S. Dublin dairy herd-level prevalence decreased from 25% in 2003 to 6% in 2015, just beforce of infection increases the demand for persistent and daily hygiene and management efforts. The lower test sensitivities (than for BVDV) lead to a requirement to perform repeated testing of herds and animals over longer time periods calling for withstanding motivation among farmers.In Slovenia, the control of bovine viral diarrhoea virus (BVDV) infections started in 1994. Since 2014, a voluntary programme has been running according to the national rules that prescribe the conditions for recognising, acquiring, and maintaining a BVDV-free status for an individual herd. The principle is based on periodical laboratory testing and preventive measures that need to be strictly implemented in a herd. Between 2014 and 2020, a total of 348 herds were included in BVDV antibody testing, and 25.0% of tested herds were detected to be BVDV antibody positive. To recognise the BVDV-free status of the herd, the breeder should provide two consecutive tests with intervals of at least 6 months in all animals in the age from 7 to 13 months, with negative results for BVDV antibodies in ELISA. The BVDV-free status of the herd can be maintained by implementing preventive measures and can be renewed each year with one laboratory test in the age group of animals from 7 to 13 months for antibodies in ELISA. During the 7 years of the voluntary programme, 236 herds were included in the detection of BVDV in individual herds by real-time RT-PCR method and the elimination of positive animals from herds. In 71 (31.3%) herds, at least one BVDV-positive animal was detected, with the identification of a total of 267 persistently infected (PI) animals, representing an average of 2.9% of tested animals. The cost of testing for an average herd, recognised as BVDV-negative, and maintaining its BVDV-free status within the implemented voluntary programme, was €97.64/year, while for the average positive herd, the laboratory costs for elimination of BVDV were €189.59/year. Only limited progress towards eradication at the national level has been achieved in Slovenia since 2014.Newborn calves are agammaglobulinemic and rely for their first immune protection almost completely on the transfer of immune constituents via colostrum. Inadequate colostrum management practices such as on-farm colostrum storage practices and colostrum feeding methods could affect immune components in colostrum and subsequently immune status of the newborn calf. We conducted a scoping review to identify all literature on the interactions between several colostrum management factors and immunological colostrum quality and passive transfer of immunity. Three major stages were defined milking methods, colostrum treatment and storage, and administration procedures. Separate CAB Abstracts searches were performed for each of the subjects of interest. The search process was completed on November 9, 2020. Colostrum should be milked as soon as possible, as IgG concentration diminishes over time, probably due to dilution. To minimize bacterial contamination, it is advised to pasteurize colostrum in small batches at maximal 60°C for 30 or 60 min. Freeze/thawing of colostrum does not or only slightly affect IgG concentrations, as long as thawing is done au bain-marie and temperature does not exceed 40°C. In on-farm situations, it is difficult to determine the volume that should be fed as the variables contributing to the absorption of IgG by the newborn calf are many and include the quality of the colostrum, the bacterial contamination, the time interval between birth and first moment of feeding and the weight of the calf. Despite all knowledge regarding optimal colostrum management strategies, it remains challenging to predict the effects of certain colostrum management choices in field conditions. Therefore, we recommend measuring the colostral quality, weighing the newborn calf, adjusting the feeding volume accordingly to ensure optimal colostrum intake for each calf.RNA-Seq data from human semen suggests that the study of the sperm transcriptome requires the previous elimination from the ejaculates of somatic cells carrying a larger load of RNA. Semen purification is also carried to study the sperm transcriptome in other species including swine and it is often done by density gradient centrifugation to obtain viable spermatozoa from fresh ejaculates or artificial insemination doses, thereby limiting the throughput and remoteness of the samples that can be processed in one study. The aim of this work was to evaluate the impact of purification with density gradient centrifugation by BoviPureTM on porcine sperm. Four boar ejaculates were purified with BoviPureTM and their transcriptome sequenced by RNA-Seq was compared with the RNA-Seq profiles of their paired non-purified sample. Seven thousand five hundred and nineteen protein coding genes were identified. Correlation, cluster, and principal component analysis indicated high-although not complete-similarity between the pumes with a distinct load of RNAs.This report describes a novel surgical technique for trans-articular external skeletal fixation (TA-ESF) of the hip to stabilize a rare, highly comminuted juxta-articular fracture of the proximal femoral segment involving the metaphysis and diaphysis in a cat. A 2-year-old, castrated male, Korean shorthair cat was admitted for a left femoral fracture caused by gunshot injury. Radiographs and computed tomography (CT) scans revealed a highly comminuted proximal femoral diaphyseal fracture that involved the femoral neck and the greater trochanter. The left femoral head was intact on CT. Under fluoroscopic guidance, an intramedullary Steinmann pin was placed to align the femur, and five positive-profile, end-threaded pins were placed in the left hemipelvis and distal femur. A triangulated frame of connecting bars was constructed using Steinmann pins and epoxy resin for TA-ESF. This secured the pins placed in the pelvis and femur as well as the intramedullary pin, providing proximal femoral stabilization by trans-articular fixation of the hip. The cat began placing weight on the left pelvic limb 4 days postoperatively, and progressively obtained near-normal limb function by day 112. The TA-ESF was partially dismantled to a linear tie-in construct on day 64 and was completely removed on day 161. Final radiographs on day 161 revealed lack of bone healing in the proximal segment, especially femoral head and neck, despite functional recovery of the injured leg. At one year postoperatively, the cat had normal limb function without any noticeable complications. On follow-up 29 months after surgery, the owner reported that the cat had normal limb function without any noticeable complications. Despite insufficient bone healing in the cat, TA-ESF of the hip allowed for satisfactory functional recovery of this challenging juxta-articular fracture of the proximal femur, which was not amenable to stabilization with a traditional non-load-sharing fixation system.Deoxynivalenol (DON) is a mycotoxin that contaminates various plant materials. Exposure to DON can disrupt hormonal homeostasis, decrease body weight gains and modulate the immune system in pigs. It can also cause diarrhea, vomiting, leukocytosis, hemorrhaging or even death. Prolonged exposure to low doses of DON can have serious health implications in mammals. This is the first in vivo study to show that per os administration of low DON doses probably contributes to specific dysfunctions in steroidogenesis processes by inducing the immunohistochemical expression of estrogen receptors alpha (ERα) in the entire gastrointestinal tract in strongly stained cells (3 points) and estrogen receptors beta (ERβ), but only in both investigated segments of the duodenum in pre-pubertal gilts. Therefore, the aim of this study was to determine whether a NOAEL dose of DON (12 μg DON/kg BW) administered per os over a period of 42 days induces changes in the immunohistochemical expression of ER in different intestinal segments and the transcriptional activation of CYP1A1 and GSTP1 genes in the large intestine of pre-pubertal gilts. This is the first report to demonstrate the expression of ER, in particular ERβ, with the associated consequences. The expression of ER was accompanied by considerable variations in the activation of CYP1A1 and GSTP1 genes, but it supported the maintenance of a stable consensus between the degree of mycotoxin exposure and the detoxifying effect in pre-pubertal gilts.Mastitis is the most common disease affecting dairy goats and causing economic losses. Although it is accepted that increased somatic cell count (SCC) is mainly a response to infection, its reliability for subclinical mastitis detection in goats is controversial. Indeed, many physiological and extrinsic variables can increase SCC, including breed, parity, age, stage of lactation, seasonal variations, and milking methods. In some animals, milk-secreting tissue is present in the wall of the teat and, in some instances, milk can filter through pores in the skin to the udder surface. This condition is known as „weeping teat” (WT). In these animals, mammary tissue might be prone to develop bacterial infections, although limited information is provided. Weeping teat seems to have a genetic background and is reported to be especially found in goat breeds selected for high milk production. Moreover, it is observed a genetic correlation between WT and decreased milk yield as well as increased somatic cell scores (SCS).