Intracranial atherosclerotic stenosis （ICAS） is an important cause of stroke worldwide， and abnormalities in lipid metabolism are major risk factors for its development and progression. Statins as lipid-lowering drugs can stabilize atherosclerotic plaques and prevent their rupture， but approximately 60% of statin users fail to achieve the goal of low-density lipoprotein cholesterol （LDL-C） recommended in guidelines， and statins are associated with the adverse effects such as drug resistance and abnormal liver function. Numerous studies have confirmed that proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors can significantly reduce the level of LDL-C and the incidence rate of atherosclerosis-associated cardiovascular and cerebrovascular events and stabilize or even reverse atherosclerotic plaques， but with limited application in ICAS. This article reviews the mechanism of action of PCSK9 inhibitors， their therapeutic efficacy in intracranial atherosclerotic stenosis， and related research advances.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

The importance of question bank construction in medical education has been well proved.However,there are still some weaknesses in the clinical teaching assessment question bank,including the inconsistency be-tween assessment and clinical practice,the lack of coherence in question bank updates,and the mismatch be-tween proposition and student learning stage.To address these issues,this article explores a teaching model which connects flipped classroom with student independent proposition and analyzes the advantages of applying flipped classroom to question bank construction.The connection between the two effectively established a regular updating mechanism for question banks,thus improve the construction of question banks in current medical education.It may support the capacity building of students' self-oriented and regulated learning and improve the quality of teaching assessment.

Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.

Post-stroke cognitive impairment (PSCI) refers to a clinical syndrome that occurs after a stroke and meets the diagnostic criteria for cognitive impairment, lasting for more than 6 months, and seriously affecting the daily life of patients. The complement system has been confirmed to be associated with PSCI. This article reviews the correlation between complement system and PSCI, as well as the possibility of complement system as an intervention target for PSCI.

Objective:To investigate the mechanism of human placenta derived mesenchymal stem cells (hPMSCs) in the inhibition of TNF-α secretion in CD4 + IFN-γ + T cells (Th1) through CD73/nuclear factor-erythroid 2-related factor 2(Nrf2) pathway to reduce liver injury in mice with graft versus-host disease (GVHD). Methods:Flow cytometry (FCM) was used to analyze the expression of TNF-α in Th1 cells and the expression of PD-1 on CD4 + IFN-γ + TNF-α + T cells (TNF-α + Th1 cells) isolated from peripheral blood and liver tissues of mice with GVHD. Hematoxylin-hosin (HE) staining, Masson staining and immunofluorescence staining were used to observe the pathological changes in liver tissues of GVHD mice in each group. HE staining was also used to observe the pathological changes in skin and lung tissues of GVHD mice. A nonconditional protocol to induce the differentiation of peripheral blood mononuclear cells (PBMCs) into Th1 cells in vitro was established. The proportion of TNF-α + Th1 cells and the mean fluorescence intensity (MFI) of Nrf2 and phosphorylated nuclear factor-kappa B (p-NF-κB) in this T cell subgroup were detected. Results:Compared with the normal control group, the proportion of TNF-α + Th1 cells and the expression of PD-1 on this T cells in peripheral blood and liver tissues of mice in the GVHD high group increased significantly ( P<0.01). The proportion of TNF-α + Th1 cells in peripheral blood and liver tissues decreased after hPMSCs treatment ( P<0.001), but the expression of PD-1 on this T cell subset was promoted in peripheral blood and liver tissues ( P<0.01, P<0.001). However, the intervention effects of shCD73 on TNF-α + Th1 cells in peripheral blood and liver tissues were significantly weakened ( P<0.05, P<0.01). Liver histopathological analysis showed that the proportion of TNF-α + Th1 cells in liver was positively correlated with Suzuki′s score, collagen area and the MFI of α-SMA ( P<0.001). Similarly, histopathological analysis of skin and lung tissues also showed that the proportion of TNF-α + Th1 cells in peripheral blood was positively correlated with skin Marina score and lung Shukai Qiao score ( P<0.001). In vitro experiment also showed that hPMSCs down-regulated the proportion of TNF-α + Th1 cells ( P<0.01) and up-regulated the expression of PD-1 on them ( P<0.05). Further analysis showed that hPMSCs could enhance the MFI of Nrf2 ( P<0.05) and weaken the MFI of p-NF-κB ( P<0.01) in TNF-α + Th1 cells. Conclusions:hPMSCs could up-regulate the expression of PD-1 through CD73/Nrf2 pathway to inhibit the formation of TNF-α + Th1 cells, thereby alleviating liver injury in GVHD mice.

Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.

Objective To explore the effects of electroacupuncture at Baihui (DU20) acupoint on learning and memory and its possible mechanism through the expression of brain-derived neurotrophic factor (BDNF) in APP/PS1 double-transgenic mice. Methods 30 female APP/PS1 double transgenic mice were randomly divided into model group, DU20 group and non-acupoint group, and 10 wild type mice con-sisted of wild group. DU20 group received electroacupuncture at Baihui and the non-acupoint group received electroacupuncture at non-acu-point for 28 days. Learning and memory was tested by Morris water maze. Deposition ofβ-amyloid (Aβ) peptide was determined by immu-nohistochemical staining. The expression of BDNF in cortex was examined by RT-PCR and Western blotting. Results Compared with the model group, DU20 group ameliorated the learning and memory ability of APP/PS1 double-transgenic mice (P<0.05), decreased the deposi-tion of Aβpeptide (P<0.05) and upregulated the gene and protein levels of BDNF (P<0.01). There was no significant difference between the model group and non-acupoint group (P>0.05). Conclusion Electroacupuncture at DU20 acupoint could ameliorate learning and memory in APP/PS1 double-transgenic mice. The mechanism may be related to increase the expression of BDNF and decrease the deposition of Aβ.