Notes

E-Selectin-Dependent Swelling and also Lipolysis in Adipose Muscle Aggravate Steatosis-to-NASH Progression via S100A8/9.
Vitamin D is considered to play an important role in musculoskeletal health. It's classical function is the regulation of calcium and phosphate homeostasis, thus ensuring a balanced bone metabolism that is characterised by an equal amount of bone resorption and bone formation. In the past decades, a plethora of pre-clinical and clinical studies reporting on potential health-beneficial properties of vitamin D have emerged. Moreover, there is an abundance of reports highlighting vitamin D deficiency and insufficiency in patients with almost innumerable diseases. Further, it is estimated that more than one billion people globally are affected by insufficient vitamin D levels. As such, research on vitamin D has been particularly popular over the past years. In orthopaedics and traumatology, most studies describe favourable effects of vitamin D in general. However, the relative importance of vitamin D is oftentimes debated. In this narrative review of the literature, we consider first, the properties of vitamin D and how vitamin D, vitamin D deficiency and the vitamin D receptor (VDR) impact on musculoskeletal health. 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. selleck chemical 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.
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