Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Objective:To identify the biotypes of blood culture positive Brucella in patients with acute brucellosis in Xinjiang Uygur Autonomous Region (hereinafter referred to as Xinjiang), and to learn about the clinical characteristics of these patients. Methods:Among the 30 patients diagnosed with acute brucellosis in First Affiliated Hospital, School of Medicine, Shihezi University from January 2019 to July 2021, the positive strains of blood culture Brucella of 12 patients with acute brucellosis were used to identify the biotype by AMOS-PCR. Then the general and clinical data of the 12 patients were collected, including demographic characteristics, epidemiological characteristics, clinical characteristics, laboratory tests, treatment and prognosis. Results:AMOS-PCR results showed that all 12 strains were Brucella melitensis. Among the 12 patients, 9 were males and 3 were females, all of whom had a clear history of livestock contact, and the onset time was concentrated in April to September. All 12 patients showed fever, followed by headache and dizziness (9/12), weakness (8/12), digestive symptoms (8/12), hyperhidrosis (7/12), lumbago and backache (6/12), and arthralgia (6/12). One patient was complicated with pleural effusion and pericardial effusion. One patient was complicated with pleural effusion, pelvic effusion and ascites. Only ascites occurred in 2 patients. Liver function was abnormal in 3 patients, lactate dehydrogenase increased in 6 patients, and blood creatinine decreased in 9 patients. Among the 12 patients, 10 patients were treated with rifampicin combined with doxycycline. The other 2 patients were treated with levofloxacin and doxycycline, supplemented by symptomatic treatment with hepatoprotective drugs due to impaired liver function. After discharge, the patients received out-of-hospital oral anti-infectious drugs for 1-2 courses (6 weeks each course), and all indicators returned to normal at 6 months and 12 months after discharge. Conclusions:All the 12 patients with acute brucellosis in Xinjiang are infected with Brucella melitensis. In addition to the common clinical features, patients are characterized by decreased creatinine and increased lactate dehydrogenase. The standardized anti- Brucella treatment is still the main treatment strategy.

Objective:To explore the MRI features of cerebral amyloid angiopathy-related inflammation (CAA-ri).Methods:The clinical and imaging data of 12 patients with CAA-ri diagnosed in Affiliated Guizhou Aviation Industry Cor Ltd No 300 Hospital of Zunyi Medical University (9 cases), Xingyi People′s Hospital (2 cases) and Anshun people′s Hospital (1 case) from June 2013 to June 2020 were analyzed retrospectively. There were 3 females and 9 males, aged from 57 to 89 years old, with an average age of 71±10 years. The twelve patients included 5 cases with probable CAA-ri and 7 cases with possible CAA-ri. The duration of the disease ranged from 30 minutes to 2 years. One patient has ApoE ε4/ε4 gene overexpressed. All the 12 patients underwent MRI, including susceptibility weighted imaging in 12 cases, DWI in 10 cases, contrast enhanced MRI (CE-MRI) in 9 cases, MRS in 3 cases, MRA in 7 cases, and perfusion-weighted imaging in 1 case.Results:Imaging features of CAA-ri included encephalopathic, tumoral, classical cerebral amyloid angiopathy(CAA) manifestations. Twelve cases of encephalopathic manifestations showed patchy white matter hyperintensity (WMH) involving U-shaped fibers on T 2 weighted fluid-attenuated inversion recovery sequence (FLAIR), usually asymmetric,with various degree of mass effect, no diffusion restriction on DWI and no enhancement on CE-MRI. One case showed a single tumoral lesion with irregular enhancement on CE-MRI. The classic CAA findings included hemorrhagic lesions (microhemorrhage in 8 cases, lobar hemorrhage in 6 cases, subarachnoid hemorrhage in 3 cases, iron deposition on the brain surface in 7 cases) and ischemic lesions (microinfarction in 1 case, enlarged perivascular space and interlobar space in 4 cases). Follow-up showed lesions absorption and/or new lesion formation in 5 cases. Conclusions:The MRI features of CAA-ri are mainly patchy WMH involving U-shaped fibers on T 2 FLAIR, usually asymmetric, with wandering and alternating features, and inconsistency with clinical manifestations.

OBJECTIVE： To study the inhibitory effect of modified Maimendong decoction combined with cisplatin on Lewis lung cancer transplantation model mice， and to explore its potential mechanism. METHODS： Lewis lung cancer transplantation mice model was induced via subaxillary inoculation of Lewis lung cancer cells. 60 mice were randomly divided into model group （normal saline， once a day， i.g.）， cisplatin group （6 mg/kg， once a week， i.p.）， modified Maimendong decoction group （20 g/kg. once a day， i.g.） and combination group （cisplatin 6 mg/kg， once a week， i.p.+modified Maimengdong decoction， once a day， i.g.）， with 15 mice in each group. All mice were treated for consecutive 2 weeks. After medication， tumor weight and thymus index were detected； HE staining was used to observe the pathological change of tumor tissue. TUNEL was used to detect apoptotic index of tumor tissue. The protein expressions of Bcl-2 and Bax were detected by Western blot assay. RESULTS： Compared with model group， tumor weight and protein expression of Bcl-2 were decreased significantly in modified Maimengdong decoction， cisplatin group and combination group （P＜0.05）， and thymus index， tumor apoptotic index and the protein expression of Bax were increased significantly （P＜0.05）. Tumor weight and protein expression of Bcl-2 in combination group were significantly lower than modified Maimengdong decoction group and cisplatin group （P＜0.05）； thymus index， tumor apoptotic index and the protein expression of Bax were significantly higher than addition and subtraction of modified Maimengdong decoction group and cisplatin group （P＜0.05）. HE staining showed that the density of tumor cells was decreased to certain degree in modified Maimengdong decoction group， cisplatin group and combination group； the area of necrosis area in the combination group was significantly larger than in modified Maimendong decoction group and cisplatin group. CONCLUSIONS： Modified Maimendong decoction can inhibit the growth of Lewis lung cancer transplanted tumor in mice by down-regulating the protein expression of Bcl-2 and up-regulating the protein expression of Bax.

To summarize the progress of researches of activated components in Chinese herbal medicine and compound preparations that resist human immunodeficiency virus in recent years.Very vast foreground of Chinese herbal medicine in the treatment of AIDS hal been elucidated.

OBJECTIVE:To explore the ward round model of clinical pharmacists.METHODS:The ward round model of clinical pharmacists was designed and explored based on clinical practice.RESULTS & CONCLUSION:Clinical pharmacists can engage in ward rounds either in cooperation with physicians or alone in special department,or by targeting at those patients using certain drugs.Each model has its distinctive characteristics and clinical pharmacists can choose suitable model based on their own level as well as the conditions in software,hardware and environment so as to facilitate rational administration.