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Tetraspanin TM4SF5 throughout hepatocytes in a negative way modulates SLC27A transporters in the course of intense essential fatty acid supply.
New data acquisition and signal processing procedures are prone to reveal bone properties beyond bone mineral quantity and to provide a more accurate assessment of bone strength.Quantitative ultrasound (QUS) presents a low cost and readily available alternative to DXA measurements of bone mineral density (BMD) for osteoporotic fracture risk assessment. It is performed in a variety of skeletal sites, among which the most widely investigated and clinically used are first the calcaneus and then the radius. Nevertheless, there is still uncertainty in the incorporation of QUS in the clinical management of osteoporosis as the level of clinical validation differs substantially upon the QUS models available. In fact, results from a given QUS device can unlikely be extrapolated to another one, given the technological differences between QUS devices. The use of QUS in clinical routine to identify individuals at low or high risk of fracture could be considered primarily when central DXA is not easily available. In this later case, it is recommended that QUS bone parameters are used in combination with established clinical risk factors for fracture. Currently, stand-alone QUS is not recommended for treatment initiation decision making or follow-up. As WHO classification of osteoporosis thresholds cannot apply to QUS, thresholds specific for given QUS devices and parameters need to be determined and cross-validated widely to have a well-defined and certain use of QUS in osteoporosis clinical workflow. Despite the acknowledged current clinical limitations for QUS to be used more widely in daily routine, substantial progresses have been made and new results are promising.Diagnostic ultrasound imaging has gained wide acceptance for a broad range of clinical uses. In many cases, ultrasonography is the first-line imaging modality selected for its ease of access and absence of ionizing radiation. Over the last decades, ultrasonography has considerably evolved and is currently contributing to important improvements in patient diagnosis and treatment. Modern ultrasound imaging can provide soft tissue anatomical (shape, size…) and functional information (tissue movements, blood flow) in 3D and 4D, characterization and distinction among tissues (echostructure) and quantification of tissue properties (microstructure, tissue stiffness). Soft tissue quantitative ultrasound (QUS) refers to methods specifically developed to assess quantitative variables reflecting tissue physical properties, usually by analyzing the raw radiofrequency signals and/or its spectral characteristics.Among the components of the blood-brain barrier (BBB), endothelial cells (ECs) play an important role in supplying limited materials, especially glucose, to the brain. However, the mechanism by which glucose is metabolized in brain ECs is still elusive. To address this topic, we assessed the metabolic signature of glucose utilization using live-cell metabolic assays and liquid chromatography-tandem mass spectrometry metabolomic analysis. We found that brain ECs are highly dependent on aerobic glycolysis, generating lactate as its final product with minimal consumption of glucose. Glucose treatment decreased the oxygen consumption rate in a dose-dependent manner, indicating the Crabtree effect. Moreover, when glycolysis was inhibited, brain ECs showed impaired permeability to molecules utilizing transcellular pathway. In addition, we found that the blockade of glycolysis in mouse brain with 2-deoxyglucose administration resulted in decreased transcellular permeability of the BBB. In conclusion, utilizing glycolysis in brain ECs has critical roles in the maintenance and permeability of the BBB. Overall, we could conclude that brain ECs are highly glycolytic, and their energy can be used to maintain the transcellular permeability of the BBB.Several individuals worldwide show cognitive impairment due to various reasons, including a prolonged lifespan and an altered lifestyle. Various causes, such as broken circadian rhythms and dopamine-related factors, have been proposed to be involved in the development of cognitive impairment. However, the underlying pathways remain elusive. Humans with circadian misalignment often face cognitive impairments, and animals with mutations in circadian rhythm-related genes display impaired cognitive functions. To analyze this in detail, this study aimed to investigate the pathways potentially involved in cognitive impairment using Period2 (Per2) transgenic animals. Spatial working memory performance in Per2 knockout (KO) and wild-type mice was assessed using the Barnes maze and Y-maze. The dopamine-related protein expression levels in the hippocampus were measured by Western blotting and enzyme-linked immunosorbent assay (ELISA). Per2 KO mice exhibited impaired spatial working memory, and the expression levels of dopamine receptor D1 (DRD1), protein kinase A (PKA), and cAMP response element-binding protein (CREB) were higher in Per2 KO mice than in control mice. Additionally, DRD1 expression levels were inversely proportional to those of PER2. Thus, memory tests were again conducted after administration of the DRD1 antagonist SCH-23390. Per2 KO mice recovered from memory impairment, and the levels of PKA and CREB decreased after treatment. The effects of Aβ on memory in Per2 mice were also investigated, and we found the increased Aβ levels did not influence the memory performance of Per2 mice after SCH-23390 treatment. These results indicate that Per2 expression levels might influence spatial working memory performance via DRD1-PKA-CREB-dependent signaling.
The anti-tumor effect of polo-like kinase 4 (PLK4) inhibitor has been explored in several neoplasms, while its synergy with bortezomib in multiple myeloma (MM) remains elusive. Hence, the present study aimed to investigate the effect of PLK4 inhibitor on the sensitivity of MM to bortezomib treatment and its underlying mechanism.

MM cell lines (RPMI-8226 and U266) were cultured in different concentrations of CFI-400945 (PLK4 inhibitor), bortezomib, or their combination. Subsequently, 740 Y-P (PI3K activator) was added in the combination of CFI-400945 and bortezomib. Besides, cell viability and apoptosis were measured by CCK-8 reagent and TUNEL apoptosis kit, separately; meanwhile, western blot was carried out for detecting PLK4, p-PI3K, PI3K, p-AKT, and AKT.

CFI-400945 and bortezomib decreased the cell viability in dose-dependent manners in MM cell lines, respectively. The combination of different concentrations of CFI-400945 and bortezomib reduced cell viability compared with monotherapy in MM cell lines (all P < 0.05). Interestingly, 200nM CFI-400945 and 4nM bortezomib showed the maximum synergy in MM cell lines. Furthermore, 200nM CFI-400945 plus 4nM bortezomib showed a better effect on decreasing cell viability and promoting cell apoptosis than CFI-400945 or bortezomib monotherapy in MM cells cell lines (all P < 0.05). Moreover, 740 Y-P alleviated the effect of bortezomib and CFI-400945 on PI3K/AKT signaling, cell viability, and apoptosis in MM cell lines.

PLK4 inhibitor plus bortezomib shows synergy in decreasing cell viability and enhancing cell apoptosis via repressing PI3K/AKT signaling in MM.
PLK4 inhibitor plus bortezomib shows synergy in decreasing cell viability and enhancing cell apoptosis via repressing PI3K/AKT signaling in MM.
To perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza.

The MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT.

Twelve trials with 1,460 patients were included. The included studies had a certain unclearthe effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.
This study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.
To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19).

This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate.

A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge raten No. ChiCTR2000030836).
To evaluate the effect and safety of low-dose of apatinib and S-1 combined with Jianpi Bushen Jiedu Decoction (JBJD) in patients with metastatic colorectal cancer (mCRC) who have failed second or above lines treatment, in order to provide more treatment option for mCRC patients by integrated medicine.

Thirteen patients were selected from a single-arm, open-label clinical study from April 2019 to September 2020. The patients were treated with low-dose apatinib (250 mg, once a day) and S-1 (20 mg, twice a day) combined with JBJD for at least one cycle and were followed up to August 2021. The primary endpoint was disease progression-free survival (PFS). AZ 960 mouse Disease control rate (DCR), objective response rate (ORR), and overall survival (OS) of patients were observed as the secondary endpoints. Adverse events were recorded as well.

The average age of the 13 patients was 56.5 ±13.0 years and 76.9% were male. The median PFS and median OS were 4.6 and 8.3 months, respectively. The ORR was 7.7% (1/13) while the DCR was 61.5% (8/13). The common adverse events were hypertension, proteinuria, elevated transaminase, and thrombocytopenia. One patient experienced thrombocytopenia of grade 3.

Patients with mCRC after failure of the second or above lines of treatment may potentially benefit from the treatment of low-dose apatinib and S-1 combined with JBJD because of its similar effect as the standard dose of target therapy and relatively better safety. (Registration No. ChiCTR1900022673).
Patients with mCRC after failure of the second or above lines of treatment may potentially benefit from the treatment of low-dose apatinib and S-1 combined with JBJD because of its similar effect as the standard dose of target therapy and relatively better safety. (Registration No. ChiCTR1900022673).
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