Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Femoral intertrochanteric fracture is one of the common types of fractures in the elderly. With the general improvement of medical and living standards, the number of elderly people is increasing, and the problem of osteoporosis has also become relatively prominent. Therefore, low violence can usually cause fractures in this area of the elderly, which has a significant negative impact on the quality of life of elderly patients. With the further development of medical technology and internal fixation materials, the emergence of proximal femoral nail antirotation(PFNA) has greatly improved the treatment effect of femoral intertrochanteric fractures in elderly patients. However, with the increasing number of patients treated, internal fixation failures have gradually been reported. In recent years, proximal femoral biomimetic intramedullary nail(PFBN) has been reported to have good clinical efficacy. Therefore, this article mainly elaborates on the theoretical basis, design characteristics, biomechanics, and clinical efficacy research of PFBN, providing more reference for the clinical treatment of femoral intertrochanteric fractures in elderly patients in the future.

Apoptosis ; Autophagy ; Ferroptosis ; Iron/metabolism* ; Sequestosome-1 Protein/metabolism* ; Ubiquitin-Specific Proteases/metabolism*

Objective:To analyze the clinical outcomes of tibial bone transport over an intramedullary nail in combination with antibiotic-loaded calcium sulphate for treatment of segmental bone defect.Methods:A retrospective analysis was conducted by enrolling 11 surgically treated patients with tibial segmental bone defect after the debridement for tibial infection or osteomyelitis who were admitted in Lower Limb Surgery Ward of Traumatic Orthopedic Department, Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from Jan. 2018 to Jan. 2020. The collected clinical materials and data included gender, age, injury mechanism, smoke or alcohol, comorbidities, intraoperative bleeding loss, bone defect length, resorption time of calcium sulphate, bone transport time, external fixation time, external fixation index, complications and Paley bone and functional criteria. SPSS 24.0 software was used to analyze the data.Results:Eleven patients were followed up for 8 to 31 months (average 23.2 months). All patients achieved bone healing and the infection was eradicated with no sign of recurrence. The mean length of defect was (8.1±1.6) cm, mean resorption time of calcium sulphate was (6.6±2.6) months, bone transport time was (11.4±2.8) weeks, external fixation time was (4.7±1.2) months, external fixation index was (0.58±0.07) month/cm and full weight bearing time was (6.1±1.4) months. The complication rate was 36.4% including deep vein thrombosis, delayed union of the docking site, pin tract infection and sterile draining of the wound. Paley bone evaluation results were excellent and good in 10 patients (90.9%) and functional results were excellent and good in 11 patients (100%).Conclusion:Tibial bone transport over an intramedullary nail in combination with antibiotic-loaded calcium sulphate is a safe, reliable and successful method for segmental bone defect and eradication of infection which reduces external fixation time and complication rate, allows patients perform weight bearing and return to daily life earlier.

Tibial fracture is a kind of common long bone fracture of extremities, most of which are complex tibial fractures caused by high energy. Because of the special anatomical structure of tibia, the incidence of postoperative complications such as malunion and nonunion is higher. This brings some difficulties to the treatment. With the patient′s higher requirements for function, doctors have a deeper understanding of biomechanics, which promotes the further development of internal fixation materials. The indications of intramedullary nails have been expanded and gradually replaced the steel plate internal fixation for the treatment of tibial fractures and achieved good therapeutic effect. This article focuses on the application and new development of intramedullary nail in the treatment of proximal, middle, distal and open tibial fractures, providing more reference for the future clinical treatment.

Objective:To report our experience in the admission and perioperative management of 88 patients with lower extremity fracture in a mildly affected area in the epidemic of COVID-19.Methods:A retrospective analysis was conducted of the 88 patients with 97 lower extremity fractures who had been admitted to Department of Orthopedic Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University College of Medicine from 23rd January, 2020 to 22nd February, 2020. They were 43 males and 45 females, aged from 15 to 95 years (average, 65.5 years). The patients underwent screening for COVID-19 infection before admission. Their fractures were located at the femoral neck in 33 cases and at the femoral trochanter in 26. Open reduction and internal fixation was performed for 29 cases, internal fixation with proximal femoral nail anti-rotation (PFNA) for 25 and hip replacement for 28. The time from injury to admission, time from admission to surgery, operation time, fracture reduction, hospital stay, and perioperative deep venous thrombosis (DVT) of lower limbs were recorded. COVID-19 infection was observed in the medical staff and patients as well.Results:All the 88 patients were COVID-19 negative in the screening before admission. The time from injury to admission averaged 4.5 days, the time from admission to surgery 3.7 days and hospital stay 6.6 days. The prostheses were all well located in the 28 patients undergoing hip replacement. The rate of functional and anatomic reduction was 94.2%(65/69) in the 69 patients undergoing internal fixation. Peri-operatively, DVT occurred in 25 cases (28.4%). High temperature was observed in 7 patients within 3 days after operation, which was diagnosed as absorption fever. No medical staff or patients were infected by COVID-19.Conclusion:In the epidemic of COVID-19, orthopedic surgeons in a medical institute in a mildly affected area can still provide effective and safe medical services for fracture patients and reduce nosocomial infection, as long as they comprehend the diagnosis and treatment guidelines for the epidemic, strictly screen the patients accordingly, stick to operative indications, protect against possible infection cautiously, and carry out the procedures in a standard manner.

Objective To explore the application of 3D-printing rapid prototyping in classification of acetabular fractures and education of young surgeons.Methods The data of 20 patients with acetabular fracture were reviewed in this study who had been treated between January and June 2016.Three junior orthopedic surgeons and 3 senior ones were chosen as observers.The conventional radiographs (X-ray films of the pelvis and acetabulum,CT scans and 3D reconstruction images of the pelvis) and 3D-printing rapid prototyping models of the 20 patients(1∶ 1) were randomly numbered.All the observers were asked to make Letournel-Judet classification of each radiograph and 3D-printing model independently in the first assessment.Four weeks later in the second assessment,all the observers were asked to make the same classifications after all the conventional radiographs and 3D-printing models were randomly numbered again.The kappa statistics was used to evaluate inter-and intra-observer agreements among the recorded results.Results At the first assessment,the inter-observer agreement was 0.887 and 0.962 respectively for conventional radiographs and 3D-printing models in senior surgeons while 0.659 and 0.849 in junior surgeons.The second assessment showed the intra-observer agreement was 0.906 for radiographs and 0.925 for 3D-printing models in senior surgeons while 0.696 and 0.849 in the junior ones.Conclusions Compared with conventional radiographs,since 3D-printing models can effectively enhance the reliability of acetabular fracture classification,they may be more helpful for young surgeons in understanding acetabular fractures.

Coronavirus ; chemistry ; ultrastructure ; Microscopy, Electron ; Models, Molecular ; Ribonucleoproteins ; chemistry ; ultrastructure

Objective To study the pretreatment with prostaglandin E1 ( PGE1 ) on acute superior mesenteric ar-tery ( SMA) ischemia reperfusion injury of intestinal cell in rats. Methods 18 healthy male SD rats were randomly divided into control group, sham operation group and experimental group. IRI of SMA model was made by clamping the SMA for one hour and two hours after reperfusion in the control group and the experimental group,respectively. PGE1(20 μg/kg) was injected from the tail vein in the control group and the experimental group. Character of pa-thology of small intestine was examined. The expression of Bax and Bcl-2 in small intestine cells and change of IF-ABP and DAO in serum were detected. Results Pathologic changes showed that there was no change in the control group;while in the sham operation group,chorionic epithelium mucosa ulceration and hemorrhage and necrosis oc-curred more seriously than that in the experimental group. Expression of Bax and Bcl-2 was higher in the sham op-eration group and the experimental group than that in the control group(P<0. 05), and it was obviously lower in the experimental group than in the sham operation group(P<0. 05). The content of IFABP and DAO in blood ser-um:it was higher in the sham operation group and the experimental group than in the control group ( P<0. 05 ) , and it was lower in the experimental group than in the sham operation group(P<0. 05). Conclusion PGE1 can relieve the alvine necrosis caused by rats' mesenteric reperfusion injury after acute artery ischemia and thus protect damaged mucosa of small intestine.

ObjectiveTo investigate the dosimetric difference in the application of RapidArc using 6 and 15 MV X-rays for radiotherapy of multiple hepatic malignancy.MethodsA total of 12 cases with multiple hepatic tumors ( primary 5 cases and secondary 7 cases) were selected.All patients underwent the three dimensional CT simulation in free breathing.For each patient,RapidArc plans with single or two 358° arcs using 6 or 15 MV X-rays were designed respectively,the prescription dose was 2Gy per fraction × 25 fractions.The dosimetric differences were compared among RapidArc plans.ResultsAll of RapidArc plans could meet the clinicalrequirement.There were no significant differences in the conformity index ( CI ),homogeneity index ( HI),the maximum dose and the minimum dose of PTV among RapidArc plans ( P ＞ 0.05).All the CI could get to 0.91 and HI could get to 0.88.In the RapidArc plans with two 358° arcs,the Vs,V10,V15 of normal liver were higher than with single arc,while V20,V25,V30,V35,V40 were lower than with single arc.There were no significant differences in the different radiation dose of normal liver,stomach,duodenum and spinal cord among different plans ( P ＞0.05 ).The monitor units of RapidArc plans using 6 MV X-rays increased 12％ compared to 15 MV averagely.CondusionThe 6 MV X-ray would be selected chiefly in the radiotherapy of multiple haptic tumor using RapidArc with whole arc(s).