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.

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 clinical effect of tumescent anaesthesia in laparoscopic cholecystectomy(LC). Methods We analyzed the data of 71 patients who underwent LC for gallbladder benign disease. Anesthesia swelling fluid was injected in 37 cases before the operation in the gallbladder triangle( group D)and another 34 cases received no injection(group C). SBP,DBP,HR and Spo2 were monitored at 4 min before gallbladder traction(T1),1 min(T2),6 min(T3)and 11 min after gallbladder traction(T4),and when the gallbladder was dissected from gallbladder bed completely(T5). The operation time,intraoperative blood loss,postoperative exhaust time,time of getting out of bed after the surgery and length of stay were recorded. The gallbladder rupture, vascular injury ,bile duct injury ,intestinal injury ,placement of drainage tube ,intra-abdominal hemorrhage , intraoperative use of atropine or ephedrine and nausea and vomiting 24 hours after the operation were recorded. Results In group C,SBP,DBP and HR were significantly decreased at T2-T4 when compared with those at T1, and were significantly lower when compared with those in group D(P < 0.05). There was no significant difference in oxygen saturation between the two groups(P > 0.05). There were shorter operation time and less intraoperative blood loss in group D when compared with those in group C and the difference was statistically significant (P <0.05). The anus exhaust time,time of getting out of bed after the surgery,length of stay,intraoperative intra-abdominal hemorrhage and nausea and vomiting in the two groups indicated no statistical significance (P > 0.05). Gallbladder damage,vascular injury,placement of drainage tube and the incidence of adverse event were less in group D than those in group C. Conclusion Swelling anesthesia in LC can shorten the operation time ,induce less postoperative complications and maintain blood circulation stability.

Purpose To perform MRI examination after the death of SD rat model due to cerebral infarction and to investigate the changing characteristics of cerebral infarction during postmortem examination. Materials and Methods Middle cerebral artery occlusion (MCAO) model was established on 21 SD rats by applying modified suture method. 13 to 56 h after modeling, 12 dead SD rats were collected for the experiment. The bodies were stored at an environment with a temperature of 10-15°C and relative humidity of 45%-55%. Head MRI was performed 12 h after modeling and at 8, 24, 48, 72 and 96 h after death respectively, and apparent diffusion coefficient (ADC) values of infarction and contralateral brain tissue were calculated. At each post-mortem time point, ADC values of bilateral cerebral hemispheres, ADC values of infarction and living infarction, and ADC values of non-infarcted brain and living non-infarcted zone were compared. Brain tissue was taken after scan for pathological diagnosis and compared with diagnostic results of postmortem MRI (pmMRI). Results The right cerebral signal of rats was abnormal 12 h after cerebral infarction and after death. Eight rats were found to have shifted cerebral middle-line structure to the left. ADC values of infarction at each time point after death were lower than that of non-infarction, the difference of which was statistically significant (P<0.05); ADC values of infarction were lower than that of living infarction, the difference of which was statistically significant (P<0.05); ADC value of non-infarcted area at each time point was lower than that of living non-infarcted area, the difference of which was statistically significant (P<0.05). Necrosis and disintegration of neurons, disintegration and liquefaction of glial fibers, infiltration of inflammatory cells and leakage of red blood cells were spotted in necrotic areas after receiving cerebral HE staining in rat. HE staining was consistent with the infarction zone indicated by pmMRI. Conclusion pmMRI can be used for the diagnosis of cerebral infarction via virtual necropsy.

Allopurinol is an inhibitor of xanthine oxidase,which is used for the treatment of gout and hyperuricemia by inhibiting uric acid synthesis thereby reducing uric acid. Allopurinol can cause severe cutaneous adverse reactions(SCAR),including drug hypersensitivity syndrome,Stevens-Johnson syn-drome (SJS),and toxic epidermal necrolysis(TEN). The study on the correlation between HLA-B*58:01 alleles and allopurinol-induced SCAR in different racial groups showed that there was a strong correlation between HLA-B*58:01 alleles and allopurinol-induced SCAR in Taiwan,Hong Kong,and the mainland of China, as well as in Thailand,Korea with high frequency of HLA-B*58: 01,while there was also an significant correlation between them in Japan and Europe with low frequency of HLA-B*58:01. Presently,there have been few studies on the specific mechanism of HLA-B*58: 01 alleles in the process of the allopurinol-induced SCAR. Representative research found that allopurinol and its metabolite oxypurinol directly and immediately activates the drug-specific T cells by bounding to HLA-B*58: 01 through the mechanism of pharmacological interaction with immune receptors,afterwards leading to SCAR.

A 32-year-old female patient with hyperthyroidism received methimazole 10 mg orally thrice daily.Three weeks later,she developed fatigue,anorexia,deep-colored urine,and pruritus of whole body skin.Methimazole was stopped.Laboratory tests showed the total bilirubin (TBil) of 463.1 μmol/L,bilirubin direct (DBil) of 348.9 μmol/L,alanine aminotransferase (ALT) of 142 U/L,aspartate aminotransferase (AST) of 64 U/L,and alkaline phosphatase (ALP) of 499 U/L.Cholestatic hepatitis induced by methimazole was considered.The patient received IV infusion of reduced glutathione,polyene phosphatidylcholine,hepatocyte growth-promoting factors,alprostadil,adenosylmethionine 1,4-butanedisulfonate,and methylprednisolone sodium succinate,and oral ursodeoxycholic acid capsules.Thirteen days later,the laboratory tests showed TBil of 432.3 μmol/L,DBil of 260.6 μmol/L,and total bile acid (TBA) of 564.0 μmol/L.The patient received 4 times of plasmapheresis within 8 days because her pruritus was not improved.On day 3 after the last plasmapheresis,laboratory tests showed TBil of 271.3 μmoL/L,DBil of 175.3 μmol/L,and TBA of 483.0 μmol/L.Liver-protective drugs and medications used to treat jaundice were continued.On day 47 after the last plasmapheresis,laboratory tests showed TBil of 22.4 μmol/L,DBil of 8.3 μmol/L,ALT of 35 U/L,AST of 20 U/L,ALP of 114 U/L,and TBA of 47.0 μmol/L.On day 51 after the last plasmapheresis,her pruritus and yellowish skin and sclera disappeared,her urine color returned to normal,and her physical strength recovered.

Allopurinol is an inhibitor of xanthine oxidase,which is used for the treatment of gout and hyperuricemia by inhibiting uric acid synthesis thereby reducing uric acid. Allopurinol can cause severe cutaneous adverse reactions(SCAR),including drug hypersensitivity syndrome,Stevens-Johnson syn-drome (SJS),and toxic epidermal necrolysis(TEN). The study on the correlation between HLA-B*58:01 alleles and allopurinol-induced SCAR in different racial groups showed that there was a strong correlation between HLA-B*58:01 alleles and allopurinol-induced SCAR in Taiwan,Hong Kong,and the mainland of China, as well as in Thailand,Korea with high frequency of HLA-B*58: 01,while there was also an significant correlation between them in Japan and Europe with low frequency of HLA-B*58:01. Presently,there have been few studies on the specific mechanism of HLA-B*58: 01 alleles in the process of the allopurinol-induced SCAR. Representative research found that allopurinol and its metabolite oxypurinol directly and immediately activates the drug-specific T cells by bounding to HLA-B*58: 01 through the mechanism of pharmacological interaction with immune receptors,afterwards leading to SCAR.