SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M^pro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent M^pro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC₅₀ values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M^pro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M^pro-CHLA complex, shrinking the substrate binding pocket of M^pro and inducing M^pro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M^pro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.

Objective:To retrospectively analyze the gender differences in the clinical characteristics and perioperative outcomes of patients with type A aortic dissection in our institution.Methods:From January 2019 to January 2020, total 405 patients underwent surgical treatment for type A aortic dissection at Beijing Anzhen Hospital, including extensive aortic repair (total aortic arch replacement combined with stenting elephant trunk implantation) and limited aortic repair. In the entire cohort, male 295 cases, female 110 cases. All measures in this study were expressed as ± s or median(quartiles) and analyzed by Student t test for variables or non- parametric tests; count data were expressed as frequencies and percentages and analyzed by χ2 test and Fisher exact probability test. Independent risk factors were analyzed by logistic multivariate regression. Results:Females were older than males[(53.3 ± 12.4)years old vs. (47.1 ± 11.0)years old, P<0.001] and had significantly higher proportion of diabetes(9.1% vs. 4.1%, P=0.047) and previous cerebrovascular disease (11.8% vs. 5.8%, P=0.038). Females had a lower proportion of total aortic arch replacement combined with elephant trunk implantation (64.5% vs. 82.7%, P<0.001), while aortic cross-clamp time[168.0(144.8, 201.5) minutes vs. 190.0 (163.0, 217.0) minutes, P<0.001] and CPB time[99.0 (79.8, 118.0) min vs. 107.0 (91.0, 126.0) min, P=0.006] were significantly shorter than males. Females had significantly higher rates of pulmonary infection (14.5% vs. 5.8%, P=0.004) and stroke than males (15.5% vs. 8.1%, P=0.030). The difference in the proportion of postoperative deaths between female and male TAAD patients was not statistically significant (3.6% vs. 7.8%). Logistics multivariable regression analysis found that female was an independent risk factor for postoperative stroke ( OR=2.574, 95% CI: 1.198-5.531, P=0.015) and pulmonary infection ( OR=2.610, 95% CI: 1.180-5.772, P=0.018). Conclusion:Gender did not affect mortality after TAAD repair significantly, but females increased the risk of stroke and pulmonary infection after TAAD surgery.

OBJECTIVE: To investigate the effectiveness of preemptive analgesia with imrecoxib on analgesia after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 160 patients with ACL injuries who met the selection criteria and were admitted between November 2020 and August 2021 were selected and divided into 4 groups according to the random number table method (n=40). Group A began to take imrecoxib 3 days before operation (100 mg/time, 2 times/day); group B began to take imrecoxib 1 day before operation (100 mg/time, 2 times/day); group C took 200 mg of imrecoxib 2 hours before operation (5 mL of water); and group D did not take any analgesic drugs before operation. There was no significant difference in gender, age, body mass index, constituent ratio of meniscal injuries with preoperative MRI grade 3, constituent ratio of cartilage injury Outerbridge grade 3, and visual analogue scale (VAS) score at the time of injury and at rest among 4 groups (P>0.05). The operation time, hospitalization stay, constituent ratio of perioperative American Society of Anesthesiologists (ASA) grade 1, postoperative opioid dosage, and complications were recorded. The VAS scores were used to evaluate the degree of knee joint pain, including resting VAS scores before operation and at 6, 24, 48 hours, and 1, 3, 6, and 12 months after operation, and walking, knee flexion, and night VAS scores at 1, 3, 6, and 12 months after operation. The knee injury and osteoarthritis score (KOOS) was used to evaluate postoperative quality of life and knee-related symptoms of patients, mainly including pain, symptoms, daily activities, sports and entertainment functions, knee-related quality of life (QOL); and the Lysholm score was used to evaluate knee joint function. RESULTS: All patients were followed up 1 year. There was no significant difference in operation time, hospitalization time, or constituent ratio of perioperative ASA grade 1 among 4 groups (P>0.05); the dosage of opioids in groups A-C was significantly less than that in group D (P<0.05). Except for 1 case of postoperative fever in group B, no complications such as joint infection, deep vein thrombosis of the lower extremities, or knee joint instability occurred in each group. The resting VAS scores of groups A-C at 6 and 24 hours after operation were lower than those of group D, and the score of group A at 6 hours after operation was lower than those of group C, and the differences were significant (P<0.05). At 1 month after operation, the knee flexion VAS scores of groups A-C were lower than those of group D, the walking VAS scores of groups A and B were lower than those of groups C and D, the differences were significant (P<0.05). At 1 month after operation, the KOOS pain scores in groups A-C were higher than those in group D, there was significant difference between groups A, B and group D (P<0.05); the KOOS QOL scores in groups A-C were higher than that in group D, all showing significant differences (P<0.05), but there was no significant difference between groups A-C (P>0.05). There was no significant difference in VAS scores and KOOS scores between the groups at other time points (P>0.05). And there was no significant difference in Lysholm scores between the groups at 1, 3, 6, and 12 months after operation (P>0.05). CONCLUSION Compared with the traditional analgesic scheme, applying the concept of preemptive analgesia with imrecoxib to manage the perioperative pain of ACL reconstruction can effectively reduce the early postoperative pain, reduce the dosage of opioids, and promote the early recovery of limb function.
Humans ; Quality of Life ; Analgesics, Opioid ; Analgesia ; Osteoarthritis, Knee ; Pain, Postoperative/prevention & control* ; Anterior Cruciate Ligament Reconstruction ; Knee Injuries

Objective:To analyze the long-term outcomes of hybrid arch repair(HAR) treating aortic arch pathologies.Methods:Between January 2009 and January 2018, 87 consecutive patients underwent HAR for aortic arch pathologies at Beijing Anzhen Hospital. 76 were males. 2 cases were in zone 0, 46 cases were in zone 1, and 39 cases were in zone 2. The zones of the aortic arch were defined following the Ishimaru classification.Results:Five(5.7%) operative death occurred. 13 patients(19.1%) died during the follow-up. The overall survival rate was 88.4%, 83.3%, 83.3%, 49.8% at 1, 3, 5, 10 year, respectively. Multivariate Cox proportional risk analysis showed that stroke( HR=20.626, 95% CI: 2.698-157.685, P=0.004) was an independent risk factor for short-term death. Stroke( HR=16.234, 95% CI: 4.103-64.229, P<0.001) and spinal cord infury( HR=11.060, 95% CI: 2.150-56.893, P=0.004) were independent risk factors for long-term death. Conclusion:In conclusion, HAR could be an alternative procedure for the patients that are not suitable for open repair under the premise of strict control of indications. In the future, the risk assessment system and uniform operational indications for HAR should be further established.

Objective:To summarize the surgical treatment strategy for aortic injury caused by trauma.Methods:From January 2009 to January 2018, 34 patients with TAI were treated in Beijing Anzhen Hospital. 10 had hypertension. 23 cases were males. There were 31 cases caused by traffic accidents, 2 cases were fall injuries, and 1 case was bruise. 9 cases were thoracic aortic pseudoaneurysm, 6 cases were thoracic aorta, and 19 cases were aortic dissection. 29 patients underwent TEVAR and 5 patients underwent OR (2 patients with type A aortic dissection undergoing Bentall + Sun's procedure, 1 patient with type B aortic dissection and 2 patients with thoracic aortic pseudoaneurysm undergoing stented elephant trunk procedure).Results:The follow-up time was (45.09±23.10) months. The mean age of patients undergoing OR or TEVAR was (44.80±20.57) years old, (45.93±11.01) years old; the mean operation time was(403.20±30.30) minutes, (105.72±27.76) minutes; the mean hospitalization (19.00±6.04), (5.76±3.08) days. There were no deaths in the two groups. 2 patients uundergoing TEVAR had left upper limb numbness.Conclusion:The treatment of patients with TAI should be based on the general condition, the classification of injury, the involving regions and anatomical features to choose different treatments. In addition, the long-term prognosis of patients remains to be determined.

In order to reduce the impact caused by the contact between the foot and the ground when wearing the lower extremity exoskeleton under the condition of high load, this paper proposed an exoskeleton foot mechanism for improving the foot comfort, and optimized the key index of its influence on the comfort. Firstly, the physical model of foot mechanism was established based on the characteristics of foot stress in gait period, and then the mathematical model of vibration was abstracted. The correctness of the model was verified by the finite element analysis software ANSYS. Then, this paper analyzed the influence of vibration parameters on absolute transmissibility based on vibration mathematical model, and optimized vibration parameters with MATLAB genetic algorithm toolbox. Finally, this paper took white noise to simulate the road elevation as the vibration input, and used the visual simulation tool Simulink in MATLAB and the vibration equation to construct the acceleration simulation model, and then calculated the vibration weighted root mean square acceleration value of the foot. The results of this study show that this foot comfort mechanism can meet the comfort indexes of vibration absorption and plantar pressure, and this paper provides a relatively complete method for the design of exoskeleton foot mechanism, which has reference significance for the design of other exoskeleton foot and ankle joint rehabilitation mechanism.
Acceleration ; Ankle Joint ; Biomechanical Phenomena ; Exoskeleton Device ; Finite Element Analysis ; Foot ; Gait ; Humans ; Lower Extremity ; Models, Theoretical ; Vibration

Sodium hyaluronate is one of the natural components of articular cartilage and synovial fluid,which plays important roles in maintaining the structure and physiological functions of joints.Abnormal change of the content and physicochemical properties of sodium hyaluronate in the joints is one of the common pathological causes of osteoarthritis.Supplementation of exogenous sodium hyaluronate,which has similar physical and chemical properties as those in normal joints,has been considered as an effective strategy for clinical treatment of osteoarthritis.However,the benefits of intra-articular injection of sodium hyaluronate are still under debates.Moreover,different recommendations for clinical use were developed in several clinical guidelines.Several guidelines suggested that molecular weight of sodium hyaluronate was an important factor influencing the clinical benefits in osteoarthritis.Diverse products of sodium hyaluronate present different physicochemical and biological characteristics,which may lead to differences in clinical efficacy and safety.High-molecular-weight sodium hyaluronate,with highly modified and cross-linked sugar chains,potentially differ from those with low molecular weight in physicochemical properties,rheological characteristics,and physiological activities.In general,high-molecular-weight sodium hyaluronate have higher viscosity and elasticity.The exogenous hyaluronate,of which the molecular weight is similar to those in normal joints,probably have the similar rheological characteristics.A large number of clinical studies demonstrated that sodium hyaluronate products with high-molecular weight significantly relieved joint pain and improved joint functions in patients with osteoarthritis.In contrast,the clinical efficacy of the low-molecular-weight hyaluronate is still controversial,because several studies could not establish the superiority in osteoarthritis when comparing with the placebo.Studies on molecular mechanisms revealed that some physiological functions of sodium hyaluronate were molecular-weight dependent.High-molecular-weight sodium hyaluronate may have more pronounced impacts on the regulation of inflammation and maintaining the homeostasis of extracellular matrix.This review focused on the effects of sodium hyaluronate with different molecular weight in treating osteoarthritis.Evidence based on clinical studies related to the molecular-weight differences of sodium hyaluronate were presented.Furthermore,the optimal use of various products of sodium hyaluronate with different molecular weight was discussed.

Objective To explore the mid-term results of the staged total aortic replacement in Stanford type A aortic dissection.Methods During March 2009 to September 2016,a total of 49 patients with Stanford type A aortic dissection in Beijing Anzhen Hospital cardiovascular center underwent total aortic replacement with a median age of 36 (27,41 years),male 36 (73.5％) cases.30 (61.2％) cases of them combined with Marfan syndrome.Results The interval between two stage operation was 23 (10,57) months.In the first stage operation,45 (91.8％) cases underwent Sun's procedure,2 (4.1％) underwent total aortic arch replacement,2 (4.1％) cases underwent classic elephant trunk and total aortic arch replacement.All patients underwent thoracoabdominal aortic repair(TAAAR).Deep hypothermic circulatory arrest surgery was 12(24.5％)cases in the second stage.7 (14.3％)cases dead postoperative.Spinal cord related complications happened in 3 (6.1％) cases with stroke in 2(4.1％) cases,acute renal insufficiency in 7(14.3 ％) cases,respiratory insufficiency in 7 cases (14.3％),re-operation for hemostasis in 3 (6.1％) cases and gastrointestinal bleeding in 3 cases(6.1％).Univariate analysis showed that the interval between two stage operation,operation time,deep hypothermic circulatory arrest surgery are risk factors for in-hospital mortality;multivariate analysis showed that deep hypothermic circulatory arrest surgery and the interval between two stage operation were independent risk factors for in-hospital mortality.3 years,5 years survival rate were 94.4％ and 78.7％.Conclusion For Stanford type A dissection especially the thoracoabdominal aortic expands,staged total aortic replacement shows good mid-term results.Block stentgraft can reduce the use of deep hypothermic circulatory arrests to decrease the mortality.

Objective To summarize the clinical outcomes and surgical indications for chronic type A aortic dissection (CTAD) by using Sun's procedure with preservation of autologous brachiocephalic vessels.Methods From September 2010 to December 2013, 23 patients with CTAD underwent Sun's procedure with preservation of autologous brachiocephalic vessels under moderate hypothermic circulatory arrest combined with selective cerebral perfusion in our center .The data was collected and analysed retrospectively.There were 20 males and 3 females patients with a mean age of(49.91 ±10.05) years.Preopera-tive comorbidities included Marfan syndrome in 1 patient, isolated left vertebral artery in 1, hypertension in 19, coronary artery disease in 2, heart dysfunction in 1, renal insufficiency in 1, mitral regurgitation in 1, and pulmonary infection in 1.Previous operation history included thoracic endovascular aortic repair in 3, percutaneous coronary intervention in 1, aortic valve re-placement in 1, Bentall procedure in 1, and coronary artery bypass grafting in 1.Results The average operation time, car-diopulmonary bypass time, aortic cross clamping time and selective cerebral perfusion time was(6.43 ±1.03) h,(167.07 ± 49.62) min,(80.74 ±29.00) min, and(27.35 ±6.03) min, respectively.Concomitant procedures included Bentall proce-dure in 6 patients, ascending aorta replacement in 17, ascending aorta-femoral artery bypass in 1, mitral valvuloplasty in 1, and CABG in 1.There were 2(8.70%) in hospital deaths.Three patients suffered temporary renal dysfunction, and 1 with re-nal failure recieved continuous renal replacement therapy .Postoperative hypoxemia were found in 2 patients, and 1 of them re-ceived reintubation.These patients recovered before discharge.The mean follow-up time was(52.52 ±9.89) months with a follow-up rate of 95.23%(20/21).One patient suffered cerebral embolism but recovered soon after treatment.The others were free from any complications.Conclusion Sun's procedure with preservation of autologous brachiocephalic vessels simplified the aortic arch surgery and obtained satisfactory outcomes for suitable patients with CTAD , but surgical indications should be strictly considered.

Objective    To evaluate the short- and middle-term outcomes of surgical treatment for distal aortic arch lesions using stented elephant trunk implantation combined with transposition of left subclavian artery to left common carotid artery. Methods    The clinical data of 14 patients with distal aortic arch lesions undergoing stented elephant trunk procedure with left subclavain artery transposition under hypothermic cardiopulmonary bypass (CPB) with antegrade selective cerebral perfusion from May 2009 to November 2015 in our hospital were retrospectively reviewed. All of them were males with a mean age of 52±14 years ranging from 20 to 69 years. Hypertension was observed in nine patients, coronary artery disease in five and prior cerebral infarction in one. History of percutaneous coronary intervention was noted in one patient, history of Bentall operation in one, ligation of patent ductus arteriosus in one and endovascular aneurysm repair in one. Results    There was no hospital death. Concomitant procedures included coronary artery bypass grafting in two patients and plasty of the ascending aorta replacement in one. Mean duration of mechanical ventilation and ICU stay was 21±7 h and 43±19 h, respectively. All patients survived and were discharged. One patient was lost to follow-up and no patient died during the follow-up. Postoperative computed tomography revealed good patency of  the anastomotic site between the left subclavian artery and the left common carotid artery. Conclusion    Stented elephant trunk procedure with left subclavain artery transposition obtains satisfactory surgical results in patients with distal aortic arch lesions.