ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells

Backgroud & AimsCurrently, the COVID-19 pandemic, caused by SARS-CoV-2 infection, represents a serious public health problem worldwide. Although it has been shown that ACE2 serves as the main receptor for SARS-CoV-2 entry into host cells, studies have shown that ACE2 is expressed at extremely low levels in various tissues, especially in some organs where virus particles have been found, such as the heart and liver. Therefore, these organs potentially express additional SARS-CoV-2 receptors that have not yet been discovered. Methods & ResultsHere, by a genome-wide CRISPR-Cas9 activation library screening, we found that ASGR1 promoted SARS-CoV-2 infection of 293T cells. In Huh-7 and HepG2 cell lines, simultaneous knock out of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary liver parenchymal cells, both of which hardly express ACE2, SARS-CoV-2 could successfully establish an infection. After treatment with ASGR1 antibody, the infection rate significantly reduced. This suggests that SARS-CoV-2 infects liver cells mainly through an ASGR1-dependent mechanism. Finally, we also found that the soluble ASGR1 could not only prevent the SARS-CoV-2 pseudovirus, which binds to the ASGR1 receptors, from infecting host liver cells, but also had a protective effect on those expressing ACE2, indicating that administration of soluble ASGR1 protein may represent a new treatment approach. ConclusionsColletively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells. Lay SummaryWe show that ASGR1 is a candidate receptor for SARS-CoV-2 to infect liver cells.

Complications in 16 out of 352 cases following femoral interlocked nail implantation Nail breakage as a main factor / 中国组织工程研究

BACKGROUND: Interlocking nail implantation exhibits great stability and preventory effect on fracture shortening or rotation.OBJECTIVE: To evaluate the reasons and countermeasures for the complication after interlocking nail implantation in treating femoral fracture.DESIGN, TIME AND SETTING: The case analysis was performed at Department of Orthopedics, Changhai Hospital of Second Military Medical University of Chinese PLA from April 1987 to April 2008.PARTICIPANTS: 352 patients underwent femoral interlocking nail implantation, including 289 male and 63 female with an average age of 35.9 years (range 18-84 years).METHODS: 127 patients were treated with close interlocking nail implantation, of which 30 cases were subjected to minimal incision to assist nail insertion; 24 were treated with dynamic interlocking nail implantation; 321 with static interlocking nail implantation, and 38 with interlocking nail implantation for femoral reconstruction.MIAN OUTCOME MEASURES: Complications post-implantation; limb joint function recovery during long-term follow-up.RESULTS: 331 cases were followed-up for over 60 months, and the longest follow-up lasted for 252 months. Complications were found in 16 cases, including deformity union in 2, femoral neck fracture in 1, exit of the nail in 2, infection in 2, breakage in 8 (nonunion in 3), and perineal nerve injury in 1. Except 2 with deformity union and recovered by secondary surgery, all patients developed bone union. During the followed-up, no pain or knocked pain was found with normal pseudoarthrosis activities and functional activities. The excellent function recovery in joints and limbs was 91.2%.CONCLUSION: Nail breakage is the main complication after interlocking nail implantation. Therefore, we should select longer and thicker interlocking nail as the first choice. In addition, the interlocked screws should be distal to fracture site. For the patients with severe trauma, the interlocking nail implantation in early stage of fracture would not increase complications.

Metal-to-metal hip surface arthroplasty in 63 cases A follow-up assessment / 中国组织工程研究

BACKGROUND: With the advanced progress of prostheses manufacture and surgical technique, early loosening of hip articulation prostheses and femoral neck fracture tend to reduce after hip surface arthroplasty. Meanwhile hip articulation activity has been improved.OBJECTIVE: To discuss the biocompatibility between the implants and the hosts in patients underwent hip surface arthroplasty and observe the functional recovery of hip articulations.DESIGN, TIME AND SETTING: Retrospective case analysis was carded out in the Department of Orthopaedics, Changhai Hospital Affiliated to the Second Military Medical University of Chinese PLA (Shanghai, China) from January 2006 to August 2007.PARTICIPANTS: Fifty-two patients with hip articulation diseases, including 25 females and 27 males, underwent sixty-three hip surface arthroplasties, and eleven cases of them were subjected to bilateral arthroplasty. Their average age was 47.6 years.METHODS: Hip resurfacing prostheses were offered by Zimmerm Company (Huntington, Indiana, USA). Hip resurfacing was performed using 4-mm-thick cement-less acetabular bone (metal acetabular cup of 3.7-ram thickness was coated with 0.3-mm plasma titanium). Acetabular cup exhibits large diameter and arch shape (165°), is coated with 0.3-ram plasma titanium and fixed with cement less. By means of posterolateral approach, acetabular prostheses were implanted to the central position of hip articulation with regards to anatomy. Acetabular prostheses were covered more than 90% area.MAIN OUTCOME MEASURES: Subsequent to the arthroplasty, biocompatibility between the implant materials and the hosts was recorded, such as dislocation and infection. Functional recovery of the patients was assessed with Harris hip score at 1, 3, 6 and 12 months after operation and annually thereafter. Radiological evaluation was conducted to record radioactive permeability in the areas of 1 ram around acetabular cup in the DeLee and Charnley zone.RESULTS: All patients were involved in the follow-up. There were no cases of dislocation, deep venous embolism, deep infection or neurovascular complications that required further treatment. The mean Harris score was 38 points before operation and significantly increased to 90 points after operation. Two patients appeared a 2-mm crevice below acetabular prostheses, which disappeared 6 months after arthroplasty. Acetabular or femoral prostheses removal, or local osteolysis was detectable.CONCLUSION: Metal-on-metal hip surface arthroplasty has excellent early effects on young and active patients. The arthroplasty potentially offers the ultimate bone preservation and better restoration of hip articulation function in patients, without specific biocompatibility.