The inherent complexity of Alzheimer's disease (AD) and failed clinical trials have spiked the interest in multifunctional ligands that target at least two key disease-associated macromolecules in AD pathology. Here we present a focused series of pleiotropic N-carbamoylazole prodrugs with dual mechanism of action. Pseudo-irreversible inhibition of the first therapeutic target, human butyrylcholinesterase (hBChE), enhances cholinergic transmission, and thereby provides symptomatic treatment, same as the standard therapeutics in use for AD. Simultaneously, this step also functions as a metabolic activation that liberates a nanomolar selective α ₂-adrenergic antagonist atipamezole, which blocks pathological amyloid β (Aβ)-induced and noradrenaline-dependent activation of GSK3β that ultimately leads to hyperphosphorylation of tau, thus achieving a disease-modifying effect. Lead compound 8 demonstrated long-term pseudo-irreversible hBChE inhibition, metabolic activation in human plasma, blood-brain barrier permeability, and p.o. bioavailability in mice. Multi-day in vivo treatment with 8 in an Aβ-induced AD murine model revealed a significant alleviation of cognitive deficit that was comparable to rivastigmine, the current drug of choice for AD therapy. Furthermore, decreased GSK3β activation and lowered tau phosphorylation were observed in APP/PS1 mice. This surpasses the symptomatic-only treatment with cholinesterase inhibitors, as it directly blocks an essential pathological cascade in AD. Therefore, these multifunctional α ₂-adrenergic antagonists-butyrylcholinesterase inhibitors, exemplified by lead compound 8, present an innovative, small molecule-based, disease-modifying approach to treatment of AD.

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

There are few reports on the use of Allium stents in the treatment of membranous urethral stricture in China. Its safety and effectiveness need to be observed. This study retrospectively analyzed the data of 5 patients admitted to our hospital for the treatment of membranous urethral stricture using Allium-covered metal urethral stents in the past 5 years. The preoperative International Prostatic Symptom Score (IPSS) score was 8.80±1.30, quality of life(QOL)score was 4.20 ±0.84, and the International Index of Erectile Function-5(IIEF-5) score was 20.20 ± 1.92, respectively. Six months after the operation, the IPSS score was 3.60±1.52, the QOL score was 1, and the IIEF-5 score was 19.80±1.48. This operation is easy with little invasion. It can alleviate the dysuria of patients with membranous urethral stricture and has little impact on the sexual function of patients. It is generally safe and controllable, but the appropriate time for implantation still needs to be explored.

COVID-19 has spread all over the world since December 2019. Although normal work and production have resumed after the epidemic has been preliminarily controlled in China, the situation of prevention and control of the re-spread of COVID-19 in China is still severe and medical institutions are still facing a great pressure in a certain period of future because part of the patients may become re-positive after healing and input cases from abroad are increasing.Based on the 2016 edition of Technical Operating Norms for Cleaning and Disinfection and Sterilization in Hospital Central Sterile Supply Department, the 2012 edition of Technical Standards for Disinfection in Medical Institutions, Prevention and Control Protocols of 2019-nCoV(5 th edition) and Diagnosis and Treatment Protocols of 2019-nCoV (6th trial version), The Central Sterile Supply Department at The Third Hospital of Hebei Medical University has worked out Recycling Procedures for Medical Instruments After 2019-nCoV Infection, Collection Procedures for Medical Instruments After 2019-nCoV Infection, and Vehicle Transport Procedures for Medical Instruments After 2019-nCoV Infection.These contingency plans may be useful references for other Central Sterile Supply Department(CSSD) during the COVID-19 epidemic.

Objective To study the clinical efficacy and safety of endoscopic papillary large balloon dilation (EPLBD) in the treatment of common bile duct (CBD) stones.Methods This retrospective study of EPLBD for CBD stoneswas conducted between May 2015 and March 2017 on 116 patients.The patients were divided into two groups based on the different methods of treatment:group A (the EPLBD group) and B(the EST + EPBD group).Results Treatment with EPLBD when compared with EST + EPBD produced similar outcomes with regard to the overall stone removal rates (96.2％ vs.93.5％,P ＞ 0.05) and complete ductal clearance in one session (92.6％ vs.92％,P ＞0.05).There were no significant differences in the rates of overall complication (22.2％ vs.22.2％,P ＞ 0.05),hemorrhage (7.4％ vs.11.3％,P ＞ 0.05),post-ERCP pancreatitis (9.3％ vs.6.6％,P ＞ 0.05) and acute cholangitis (5.6％ vs.8.1％,P ＞0.05).When compared with EST + EPBD,mechanical lithotripsy was performed less in the EPLBD group (16.6％ vs.27.4t％,p ＜ 0.05).Conclusions EPLBD was an effective and safe method to treat CBD stones.EPLBD reduced the use of mechanical lithotripsy when compared with EST + EPBD.

Objective To evaluate the capability of Turbo inversion recovery magnitude (TIRM) magnetic resonance neurography (MRN) in the diagnosie of sacral plexus injury by comparing MRN findings with surgical results.Methods Ten patients with sacral plexus injury confirmed surgically underwent conventional T1WI,T2WI,TIRM and coronal TIRM MRN before operations from June,2011 to December,2012.The MRI data and surgical data were analyzed retrospectively to observe nerve injury.Results The coronal TIRM MRN images displayed 93 trunks of sacral plexus,of which 37 were confirmed injury by operation.The MRI findings were as follows:6 trunks involved continuous nerves,but with thickening and blurred margin,as well as abnormal high signal intensity;22 trunks were continuous,but with distortion,stiffness and adhesion accompanied by heterogeneous signal intensity and structural disorder;3 trunks showed complete loss of continuity,absence of normal signal,accompanied by retraction;and 3 trunks involved formation of traumatic neurofibroma.The coincidence of injured nerve trunks diagnosed by MRN with surgical findings amounts to 81.08％ (30/37).Conclusion MR with coronal TIRM imaging is effective in the diagnosis and depiction of sacral plexus injury,therefore it can be used as conventional sequence in sacral plexus examination to detect sacral plexus avulsion.

Objective To investigate the significance of miR-193b to biological behaviors of hepatocellular carcinoma (HCC). Methods 48 cases of HCC specimens and corresponding adjacent tissues were collected, and the miR-193b expression levels in these specimens were measured by real-time quantitative PCR. The miR-193b expression was measured by the same way in HepG2 and SMMC-7721 cells. The HepG2 and SMMC-7721 were transfected with miR-193b mimics or negative control miRNA mimic with Lipofectamine 2000, and the non-transfected cells were taken as blank control. The proliferation ability of the HCC cells were detected by MTT method, and the apoptosis rate was tested by flow cytometry. Results The expression level of miR-193b in HCC tissues (2.441 ±0.569) was significantly lower than that in the corresponding adjacent tissues (15.488±4.326) (P < 0.05). Compared with normal liver cell line L-O2, the expression levels of miR-193b were significantly lower in HepG2 and SMMC-7721 cells. Transfected with miR-193b mimic, the proliferation ability of HepG2 and SMMC-7721 cells were reduced, while their apoptosis were increased. Conclusion miR-193b may be negative to regulate the proliferation of HCC and increase its apoptosis.

Objective To explore the law of apoptosis of lumbar spinal cord neurons in cauda equina syndrome (CES). Methods Cauda equina of rats was compressed by a piece of silica gel stick. From day 1 to day 28, the lumbar spinal cord specimens were harvested and assessed by Nissl's staining and TUNEL staining. Results Compression of cauda equina caused lesion and apoptosis of neurons in lumbar spinal cord, and the extent of apoptosis reached the peak on 7th day after compression. Conclusion Apoptosis of neurons in lumbar spinal cord might be one of the reasons why patients with CES get poor prognosis.