ABSTRACT
Coronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020; www.who.int)1. While fatality rates are higher among the elderly and those with underlying comorbidities2, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.3-7 We report that the autoimmune PTPN2 risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.
ABSTRACT
Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.Competing Interest StatementThe authors have declared no competing interest.View Full Text
ABSTRACT
Objective To explore surgical techniques and curative effects of microsurgical treatment for tumors in upper cervical spinal canal.Methods A total of 81 cases of tumors in upper cervical spinal canal had received microneurosurgery from January 1990 to December 2005.The operation was conducted through a posteromedial approach.A total tumor resection was performed in 73 cases of neurofibroma or neurilemmoma,3 cases of spinal meningioma,and 3 cases of ependymoma.A subtotal tumor resection was conducted in 2 cases of astrocytoma.Results A complete recovery was achieved in 75 cases,an improvement of symptoms was achieved in 4 cases,and no improvement in 2.No death was encountered.Follow-up observations were carried out in 52 cases for 3 months ～ 3 years(8.5?1.5 months).MRI examinations 3 months after operation in 15 cases found no residual or recurrent tumor.X-ray radiography under anteroposterior,lateral,and open-mouth view 6 months after operation in 32 cases showed no spinal deformation and good vertebral stability.Recurrence of intramedullary tumor was seen in 3 cases. Conclusions As long as tumors in upper cervical spinal canal are diagnosed,a microsurgical treatment should be given as early as possible.Appropriate selection of surgical approach,skillful microsurgical techniques in accordance with pathological types of lesions,and principles of minimal invasion are critical for the operation safety.
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Objective To investigate the long-term effects of microendoscopic discectomy for lumbar intervertebral disc herniation. Methods A retrospective analysis was made on 218 cases of lumbar intervertebral disc protrusion treated by microendoscopic discectomy. The Japanese Orthopedic Association (JOA) scoring system for lumbar myelopathy was used to evaluate surgical outcomes for each patient. Results All the patients were followed for more than 3 years postoperatively. Excellent outcomes were achieved in 121 cases, good in 80 cases, fair in 16, and poor in 1, the rate of excellent or good outcomes being 92.2% (201/218) . Conclusions Microendoscopic discectomy for lumbar intervertebral disc herniation has definitive long-term effects. Skillful surgical performance and proper postoperative rehabilitation training are crucial to good surgical outcomes.
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Objective To explore the surgical techniques of keyhole approach craniotomy in the treatment of hypertensive intracerebral hemorrhage in old patients. Methods CT-guided keyhole approach craniotomy was performed to treat 50 old patients with hypertensive hematomas from January 2000 to August 2003. Results CT scans within 12 postoperative hours showed over 90% hematomas were removed. The activity of daily living (ADL) classification results 6 months after the surgery were: grade Ⅰin 10 cases (20.0%), grade Ⅱ in 21 cases (42.0%), grade Ⅲ in 9 cases (18%), grade Ⅳ in 3 cases (6.0%), grade Ⅴ in 2 cases (4.0%), and grade Ⅵ in 5 cases (10.0%). Conclusions Senility is by no means a contraindication for surgery in the treatment of hypertensive hematomas and keyhole approach minimally invasive craniotomy can give a satisfactory effect.
