Inhibition of CDK1 attenuates neuronal apoptosis and autophagy and confers neuroprotection after chronic spinal cord injury in vivo.

Chronic spinal cord injury (CSCI) results from progressive compression of the spinal cord over time. A variety of factors cause CSCI, and its exact pathogenesis is unknown. Cyclin-dependent kinase 1 (CDK1) is closely related to the apoptosis pathway, but no CSCI-related studies on CDK1 have been conducted. In this study, the role of CDK1 in CSCI was explored in a rat model. The CSCI model was established by screw compression using the cervical anterior approach for twelve weeks. The neurological function of the rats was evaluated using the neurological severity scores (NSS) and motor evoked potentials (MEPs). Pathological changes in spinal cord tissue were observed by hematoxylin-eosin (HE) staining, and Nissl staining was performed to assess the survival of motor neurons in the anterior horn of the spinal cord. Changes in autophagy and apoptosis in anterior horn of spinal cord tissue were detected using transmission electron microscopy and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. The expression levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor (IBA) and choline acetyltransferase (CHAT) in the anterior horn were determined using immunohistochemistry assays to investigate astrocytes, microglia and motor neurons, respectively, in the anterior horn. Western blot assays were used to detect the expression levels of CDK1, Bcl-2, Bax, Caspase 3, LC3 and Beclin1. Changes in the expression of CDK1, LC3 and Beclin1 were also observed using immunohistochemistry. The results indicated that CSCI resulted in neuronal injury and a decrease in the NSS. In the CSCI model group, anterior horn astrocytes and microglia were activated, and motor neurons were decreased. Neuronal apoptosis was promoted, and the number of autophagic vacuoles was elevated. Rats treated with the CDK1 shRNA lentivirus exhibited better NSS, more surviving motor neurons, and fewer apoptotic neurons than the model rats. The occurrence of autophagy and the expression of proapoptotic and autophagy-related proteins were lower in the CDK1 shRNA group than the model group. In conclusion, CDK1 downregulation suppressed the activation of anterior horn astrocytes and microglia, promoted motor neuron repair, and inhibited neurons apoptosis and autophagy to promote the recovery of motor function after spinal cord injury.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

[Treatment of scapular fractures with lateral incision and bridge combined internal fixation system].

OBJECTIVE: To investigate the clinical results of scapula fractures with lateral incision combined with bridge internal fixation system. METHODS: From October 2012 to December 2016, 20 cases of scapular fractures were treated through the lateral incision combined with bridge fixation system, including 15 males and 5 females, with an average age of 31.6 years old(ranged, 21 to 52 years old). Fourteen cases were scapular body fracture, 10 were scapular neck fracture, 6 were scapular fracture, 1 was acromion fracture, 1 was coracoid fracture, 4 were the glenoid rim fracture, 3 were the glenoid fossa fracture. The operation time ranged from 4 to 15 d after injury with an average of 10 d. RESULTS: All 20 cases were followed up for 3 to 24 months with an average of 15 months. Wound infection occurred in 2 cases after operation, and was healed after wound debridement and change dressing; no osteomyelitis, iatrogenic nerve injury, breakage of internal fixation, fracture displacement, joint stiffness occurred. Callus growth was observed at the fracture site 3 months after operation, the fracture healing time was 4 to 7 months, fracture healing was good without delayed union or malunion. According to Hardegger shoulder score, the results were excellent in 12 cases, good in 6 cases, moderate in 2 cases. CONCLUSIONS: Lateral incision approach combined with bridge internal fixation system for scapula fractures has the advantages of easy operation, revealed clearly, and the incision can be arbitrary to extend on both sides, to provide favorable conditions for the reduction and fixation of fracture. Bridge combined internal fixation system has the advantages of flexible operation, reliable fixation strength, is a good choice for treatment of scapula fracture.

An accurate and reproducible scheme for quantification of coronary artery calcification in CT scans.

The coronary artery disease is a major cause of deaths in the western world. One indicator for coronary artery disease (CAD) is coronary artery calcification (CAC). An accurate and reproducible scheme is desired to monitor the progression of patient's coronary calcification in follow-up studies. Traditional approaches for CAC estimation lack to provide accurate and reproducible results. In This work, a new adaptive and stochastic 3D method has been proposed by employing a modified expectation-maximisation (MEM) algorithm. It is less sensitive to partial volume effects, motion effects, slice thickness and low dose. Accuracy of the proposed method was measured by a cardiac CT stationary phantom containing 6 calcium inserts of predetermined size and density that were scanned 90 times using 15 different protocols based on slice thickness and radiation. Reproducibility was measured in 35 patients who were each scanned twice with the patient being repositioned before the second scan. Compared with the Agatston based method, it is shown that the proposed algorithm gives better results in terms of accuracy and reproducibility.