The Role of TREM2 Receptor in Alzheimer’s Disease / 中山大学学报(医学科学版)

Alzheimer's disease （AD） is the most common form of senile dementia， and its pathogenesis is still unclear. While β-amyloid （Aβ） is considered an important cause of AD， the pathological mechanism of Aβ inducing AD is subject to various controversies. Recent studies have shown that the myeloid cell trigger receptor （TREM2） plays an important role in the pathological process of AD， and it can not only serve as an important receptor for the internalization of Aβ but also become a biological diagnostic biomarker and therapeutic target. Hence， elucidating the structure and function of TREM2 will provide important ideas for the prevention and treatment of AD. This article will provide a systematic review of the structure of TREM2， its impact on microglial cell function， its pathological role in AD， and the current status of targeted TREM2 therapy for AD. These summaries will provide valuable references for basic research on AD.

Effect of panaxydol on ventilator-induced lung injury in mice: relationship with Keap1/Nrf2 signaling pathway / 中华麻醉学杂志

Objective:To evaluate the effect of panaxydol on ventilator-induced lung injury(VILI) in mice, and the relationship with Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2) signaling pathway.Methods:Fifty healthy clean-grade male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (group C), VILI group, low-dose panaxydol group (L-PX group, 5 mg/kg), medium-dose panaxydol group (M-PX group, 10 mg/kg) and high-dose panaxydol group (H-PX group, 20 mg/kg). The corresponding doses of panaxydol were intraperitoneally injected for 7 consecutive days once a day in L-PX group, M-PX group and H-PX group. The equal volume of normal saline was given instead in C group and VILI group. Only tracheotomy was performed and animals kept spontaneous breathing for 4 h in group C, and the animals were mechanically ventilated (tidal volume 30 ml/kg, respiratory rate 70 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%) for 4 h in VILI, L-PX, M-PX and H-PX groups. Blood samples from the femoral artery were collected for arterial blood gas analysis at 4 h of ventilation, and PaO 2 was recorded. The mice were then sacrificed under deep anesthesia, and bronchoalveolar lavage fluid (BALF), lung tissues and serum samples were collected. The concentrations of TNF-α and IL-1β in BALF and serum were measured by enzyme-linked immunosorbent assay. The wet/dry lung weight (W/D) ratio was measured, the protein concentrations in BALF were measured by bicinchoninic acid assay, the pathological changes of lung tissues were examined by HE staining, lung injury was scored, and the level of ROS in lung tissues was detected by DCFH-DA fluorescence probe.The expression of Keap1 and Nrf2 in lung tissues was detected by Western blot. Results:Compared with group C, the PaO 2 was significantly decreased, the lung injury score, W/D ratio, protein concentrations in BALF and concentrations of TNF-α and IL-1β in BALF and serum were increased, the expression of Keap1 and Nrf2 was up-regulated, and the fluorescence of ROS was enhanced in the other four groups ( P<0.05). Compared with group VILI, PaO 2 was significantly increased, the lung injury score was decreased, lung W/D ratio, protein concentrations in BALF, and concentrations of TNF-α and IL-1 β in BALF and serum were decreased, and the fluorescence of ROS was weakened in L-PX, M-PX, and H-PX groups, and the expression of Keap1 was down-regulated, the fluorescence of ROS was weakened, and the expression of Nrf2 was up-regulated in M-PX and H-PX groups ( P<0.05). Compared with group L-PX, PaO 2 was significantly increased, the lung injury score, W/D ratio, protein concentrations in BALF and concentrations of TNF-α and IL-1β in BALF were decreased, the expression of Keap1 was down-regulated, and the expression of Nrf2 was up-regulated and the fluorescence of ROS was weakened in M-PX and H-PX groups ( P<0.05). Compared with group M-PX, PaO 2 was significantly increased, the lung injury score, W/D ratio, protein concentrations in BALF and concentrations of TNF-α and IL-1β in BALF were decreased, the expression of Keap1 was down-regulated, the expression of Nrf2 was up-regulated, and the fluorescence of ROS was weakened in H-PX group( P<0.05). Conclusions:Panaxydol can reduce VILI in mice, and the mechanism may be related to activation of the Keap1/Nrf2 signaling pathway and inhibition of oxidative stress.

Progress in the prevention and treatment of traditional Chinese medicine based on the mechanism of intestinal injury of various chemotherapy / 中国临床药理学与治疗学

Intestinal injury is a common adverse reaction of clinical chemotherapy drugs, which limits the further application of chemotherapy drugs and causes serious physical and mental burden to patients. At present, the mechanism of chemotherapy-induced intestinal injury is complex, and traditional Chinese medicine has an excellent preventive effect. This article reviews the related mechanisms of intestinal flora imbalance, oxidative stress, inflammatory response, cell apoptosis, and immune damage caused by chemotherapy, and summarizes the role of traditional Chinese medicine in prevention and treatment of oxidative stress, inflammatory response, cell apoptosis, and immune damage.

Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia / 医学前沿

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as DUX4 rearrangements, MEF2D rearrangements, ZNF384/ZNF362 rearrangements, NUTM1 rearrangements, BCL2/MYC and/or BCL6 rearrangements, ETV6-RUNX1-like gene expression, PAX5alt (diverse PAX5 alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic PAX5 alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.

Clinical significance of CD34 / 医学前沿

t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34

The application of magnetic resonance imaging in postoperative delirium / 中国医师进修杂志

Postoperative delirium is one of the most common postoperative complications in elderly patients,and its pathogeny is related to many factors.Up to now,the neural basis of postoperative delirium is unclear, and whether it will develop to Alzheimer's disease is controversial. Magnetic resonance imaging (MRI), as a noninvasive and quantitative method for the analysis of brain structures and functions,has been gradually applied to a variety of neuropsychopathic disorders in recent years.The purpose of this study is to investigate the use of MRI in the studies of postoperative delirium.

Effects of Dexmedetomidine on the Lung Compliance and the Expression of TLR-2 and TLR-4 in the Peripheral Blood during Perioperative Period in Patients Undergoing Open Colorectal Cancer Radical Surgery / 中国医科大学学报

Objective To evaluate the effects of dexmedetomidine on perioperative pulmonary compliance and the expression of Toll?like recep?tor(TLR)?2 and TLR?4 in the peripheral blood during perioperative period in patients undergoing open colorectal cancer radical surgery. Meth?ods Twenty patients with colorectal cancer underwent elective general anesthesia,with ASA gradeⅠ?Ⅱand body mass index(BMI)<30 kg/m2, aged 30 to 68 years old,were enrolled for the study. They were randomly divided into control group(group C,n=10)and dexmedetomidine group (group D,n=10). In group D,dexmedetomidine was infused at a rate of 0.4μg·kg-1·h-1 from the beginning of surgery till 30 min before the end of surgery. The patients in group C received same manipulation as in group D except dexmedetomidine was replaced by normal saline. The mean ar?terial pressure(MAP)and heart rate(HR)were recorded before anesthesia induction(T0),30 min(T2),60 min(T3),and 90 min(T4)after the beginning of surgery,extubation(T6),and 3 min after extubation(T7). Airway pressure and lung dynamic compliance were recorded at T1?T7 time points,respectively. Vein blood samples were drawn to analyze the TLR?2,TLR?4 and tumor necrosis factorα(TNF?α)concentration at T0,T4,T7 and the day after operation(T8),respectively. Results Compared with group C,MAP and HR increased in group D at T6(P<0.05);lung dynamic compliance increased in group D at T4(P<0.05);TLR?2 and TLR?4 concentration in serum decreased in group D at T4, T7 and T8(P<0.05);TNF?αconcentration in serum decreased in group D at T4,T7 and T8(P<0.05). Conclusion Continuous infusion of 0.4μg·kg-1·h-1 dexmedetomidine can help to stabilize hemodynamics,relieve inflammatory stress response,maintain the relative stability of intra?operative hemodynamic parameters,and also can improve the pulmonary dynamic compliance of patients.