Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer / 中华肿瘤杂志

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

Ilizarov bone transport assisted by a 3D printed patient-specific guide plate for treatment of tibial bone defects / 中华创伤骨科杂志

Objective:To evaluate the efficacy of 3D printed patients-specific guide plates in assisting Ilizarov bone transport in the treatment of tibial bone defects.Methods:A retrospective study was conducted to analyze the clinical data of 24 patients with tibial bone defects who had been admitted to Institute of Trauma Orthopedics, The 80th Army Group Hospital of PLA from January 2018 to March 2022. There were 9 males and 15 females with an age of (49.8±6.5) years, and 4 upper tibial defects, 5 middle tibial defects, and 15 lower tibial defects. According to the methods of repairing bone defects, the patients were divided into 2 groups: a 3D printing group of 10 cases where a 3D printed patient-specific guide plate was used to assist Ilizarov bone transport in the treatment of tibial bone defects, and a traditional group of 14 cases where Ilizarov bone transport was performed in a traditional manner. The 2 groups were compared in terms of operation time, frequency of intraoperative fluoroscopy, axial angulation of the tibia at postoperation and the last follow-up, external fixation time (EFT) and external fixation index (EFI). At the last follow-up, healing of bone defects was evaluated according to the criteria of The Association for the Study and Application of the Method of Ilizarov (ASAMI), functional outcomes were evaluated according to the Paley criteria, and needle infection was recorded according to the Paley classification for complications.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (11.3±2.0) months on average after operation. The 3D printing group had significantly shorter operation time [(19.9±2.6) min] and significantly lower frequency of intraoperative fluoroscopy [(3.0±0.8) times] than the traditional group [(38.1±2.2) min and (8.9±1.3) times] (P<0.05), and had significantly better axial angulation of the tibia at postoperation and the last follow-up than the traditional group ( P<0.05). There was no significant difference in EFT or EFI between the 2 groups ( P>0.05), and the last follow-up revealed no significant difference either in bone healing, functional outcomes, or needle infection between the 2 groups ( P>0.05). Conclusion:In the treatment of tibial bone defects, compared with conventional Ilizarov bone transport, the Ilizarov bone transport assisted by a 3D printed patient-specific guide plate demonstrates advantages of shorter operation time, lower intraoperative fluoroscopy, and higher reduction accuracy.

Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023) / 中华创伤杂志

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults (version 2023) / 中华创伤杂志

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Clinical guideline for diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture (version 2023) / 中华创伤杂志

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

The correlation between the efficacy of escitalopram and the traditional Chinese medicine syndrome types of depressive disorders:a randomized controlled study / 中国药理学与毒理学杂志

OBJECTIVE To clarify whether the thera-peutic effect of escitalopram on depression patients is cor-related with traditional Chinese medicine syndrome types,and to provide a basis for more accurate drug applica-tion.METHODS A total of 235 depression patients were recruited and classified according to traditional Chinese medicine syndrome differentiation into 5 types:liver and qi stagnation(45),liver stagnation and fire transformation(43),liver qi stagnation and spleen deficiency(79),heart and spleen deficiency(20),and liver and kidney deficiency(38).All patients were treated with escitalopram(10 mg·d-1)for eight weeks.The Montgomery Depression Rating Scale(MADRS)and the 17 Hamilton Depression Rating Scale(HAMD-17)were used to score before treatment and 2,4,and 8 weeks after treatment,respectively.RESULTS Compared with before treatment,the MADRS and HAMD-17 scores and remission rates of each syn-drome type significantly improved with increasing medica-tion duration.The MADRS score relief rate of liver and kidney deficiency type was the most significant(69.3%),significantly higher than the other four syndrome types(47.5%-52.6%,P<0.05);The remission rate of HAMD-17 score was significantly higher than that of heart and spleen deficiency(50.7%vs.28.5%,P＜0.05).The remis-sion rate of HAMD-17 score in liver and qi stagnation type(52.2%)was significantly higher than that in liver stagnation and spleen deficiency type(37.0%,P＜0.01)and heart spleen deficiency type(28.5%,P＜0.05).CON-CLUSION Escitalopram may have a more significant therapeutic effect on patients with liver and kidney defi-ciency and liver stagnation depression.This study pro-vides a new approach for the more effective and accu-rate application of traditional Chinese medicine syndrome differentiation in the selection of clinical antidepressants.

Validation of the detection method for residual human coagulation factor Ⅺ in human prothrombin complex / 中国输血杂志

【Objective】 To establish an enzyme-linked immunosorbent assay (ELISA) method for the determination of residual human coagulation factor Ⅺ in human prothrombin complex and validate the method. 【Methods】 Human factor Ⅺ was reacted with the capture antibody coated on the microtiter plate. After appropriate washing steps, biotinylated primary antibody was bound to the captured protein. Excess primary antibody was washed away and bound antibody was reacted with horseradish peroxidase conjugated streptavidin. TMB substrate was used for color development at 450 nm. The dilution reliability, accuracy, specificity, repeatability, intermediate precision, linearity, range and durability were verified. 【Results】 The verification results showed that the accuracy and specificity of this method met the experimental requirements, with an average recovery rate of 109.2% and RSD of 6.93%. The repeatability RSD was 6.78%, and the intermediate precision RSD was 6.75%, indicating good precision. The linear regression correlation coefficient of standard curve was 0.999 9, showing good accuracy and precision within the linear range. The durability was verified by the incubation time and the validity period of reagent kit opening. The results showed that the RSD of the incubation time change was 6.62%, indicating that the incubation time of this detection method was controlled between 28 to 32 minutes, and there was no significant impact on the results. The RSD of the detection results before and after the reagent kit was opened and stored under conditions for 7 days was 3.84%, indicating that the preservation of the reagent kit according to the conditions for 7 days after opening has no effect on the FⅪ detection results. Both indicated that the method had good durability. The dilution reliability results showed that there was a "hook" effect in the detection of FⅪ residue in human prothrombin complex, which could be solved by diluting 100 to 200 times. 【Conclusion】 This method can be used for the determination of FⅪ residues of human prothrombin complex in laboratory.

Mechanical Thrombectomy for Refractory Cerebral Venous Sinus Thrombosis in a Child with Nephrotic Syndrome : A Case Report

Nephrotic syndrome (NS) is associated with cerebral venous sinus thrombosis (CVST), which is a rare cerebrovascular disorder in children. Systemic anticoagulation with heparin is the standard therapy for CVST, and mechanical thrombectomy (MT) has been described as a salvage treatment for adult anticoagulant refractory CVST, However, it has never been reported in children. We describe a case of MT for refractory CVST in a child with NS. A 13-year-old boy with newly diagnosed NS presented to an emergency department with acute headache. A head computed tomography showed acute thrombus in the superior sagittal sinus, straight sinus and transverse sinus. The child was started on heparin therapy, but clinically deteriorated and became unresponsive. In view of the rapid deterioration of the condition after anticoagulation treatment, the patient received intravascular treatment. Several endovascular technologies, such as stent retriever and large bore suction catheter have been adopted. After endovascular treatment, the patient’s neurological condition was improved within 24 hours, and magnetic resonance venography of the head demonstrated that the CVST was reduced. The child recovered with normal neurological function at discharge. This case highlights the importance of considering MT for refractory CVST, and we suggest that MT may be considered for refractory CVST with NS in children.

Recent advances of antiviral drugs based on multispecific binding strategy / 药学学报

To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

Recent advances of small molecule inhibitors directly targeting HBV / 药学学报

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Recent advances in small-molecule inhibitors targeting influenza virus glycoproteins / 药学学报

Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.

Preparation, crystal structure and thermostability of nirmatrelvir polymorphs / 药学学报

The polymorphism and thermostability of nirmatrelvir, the main antiviral component of the oral COVID-19 treatment drug, were studied. Four polymorphs of nirmatrelvir were prepared by recrystallization methods. Among them, Form 1 and nirmatrelvir methyl tert-butyl ether solvate (Form 2) had been reported in the literature, while nirmatrelvir isobutyl acetate solvate (NMTW-IBAC) and nirmatrelvir ethyl acetate solvate (NMTW-EA) are two new solvates. The crystal structures were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The thermostability of polymorphism and crystalline transformation were also investigated by combining Hirshfeld surface analysis and interaction energy analysis. The results showed that nirmatrelvir Form 1 belongs orthorhombic crystal system with the space group P212121 and one nirmatrelvir molecule included in the asymmetric unit, which has the same crystal structure as nirmatrelvir Form 4 reported in the literature. Owing to its larger thermal expansion, the differences in crystallographic parameters obtained at different temperatures were found between Form 1 and Form 4. Three solvates of nirmatrelvir belonged to the iso-structural with monoclinic crystal system and the space group P21, in which the asymmetric unit contains one nirmatrelvir molecule and one solvent molecule. The thermal analysis results showed that nirmatrelvir Form 1 was a solvent-free crystal form with the best thermal stability and the strongest intermolecular hydrogen bonding. Among the three solvates, NMTW-EA has the worst thermal stability and the weakest hydrogen bonding interaction between the nirmatrelvir molecule and the solvent molecule. The energy framework of nirmatrelvir solvates showed that the closer the arrangement between solvent and nirmatrelvir molecules, the greater the total interaction energy between solvent and nirmatrelvir molecules. The phase transition studies of the three solvates showed that NMTW-IBAC and NMTW-EA were transformed into amorphous after desolvation, respectively, while Form 2 undergoes oiling during desolvation. The research provides theoretical guidance for the analysis, identification and quality control of nirmatrelvir polymorphs.

Advances in research on small molecule regulators targeting HBV cccDNA generation and transcription / 药学学报

Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.

Research progress of SARS-CoV-2 main protease inhibitors / 药学学报

As a common protease with high similarity among coronavirus species, the main protease (Mpro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

Application of artificial intelligence based on data enhancement and hybrid neural network to site identification during esophagogastroduodenoscopy / 中华消化内镜杂志

Objective:To evaluate artificial intelligence constructed by deep convolutional neural network (DCNN) for the site identification in upper gastrointestinal endoscopy.Methods:A total of 21 310 images of esophagogastroduodenoscopy from the Cancer Hospital of Chinese Academy of Medical Sciences from January 2019 to June 2021 were collected. A total of 19 191 images of them were used to construct site identification model, and the remaining 2 119 images were used for verification. The performance differences of two models constructed by DCCN in the identification of 30 sites of the upper digestive tract were compared. One model was the traditional ResNetV2 model constructed by Inception-ResNetV2 (ResNetV2), the other was a hybrid neural network RESENet model constructed by Inception-ResNetV2 and Squeeze-Excitation Networks (RESENet). The main indices were the accuracy, the sensitivity, the specificity, positive predictive value (PPV) and negative predictive value (NPV).Results:The accuracy, the sensitivity, the specificity, PPV and NPV of ResNetV2 model in the identification of 30 sites of the upper digestive tract were 94.62%-99.10%, 30.61%-100.00%, 96.07%-99.56%, 42.26%-86.44% and 97.13%-99.75%, respectively. The corresponding values of RESENet model were 98.08%-99.95%, 92.86%-100.00%, 98.51%-100.00%, 74.51%-100.00% and 98.85%-100.00%, respectively. The mean accuracy, mean sensitivity, mean specificity, mean PPV and mean NPV of ResNetV2 model were 97.60%, 75.58%, 98.75%, 63.44% and 98.76%, respectively. The corresponding values of RESENet model were 99.34% ( P<0.001), 99.57% ( P<0.001), 99.66% ( P<0.001), 90.20% ( P<0.001) and 99.66% ( P<0.001). Conclusion:Compared with the traditional ResNetV2 model, the artificial intelligence-assisted site identification model constructed by RESENNet, a hybrid neural network, shows significantly improved performance. This model can be used to monitor the integrity of the esophagogastroduodenoscopic procedures and is expected to become an important assistant for standardizing and improving quality of the procedures, as well as an significant tool for quality control of esophagogastroduodenoscopy.

Clinical characteristics and risk factors of superior mesenteric artery ischemic disease / 中华普通外科杂志

Objective:To explore the clinical characteristics of superior mesenteric artery ischemic diseases.Methods:The clinical and followup data of 141 hospitalized patients with ischemic disease of superior mesenteric artery in the Affiliated Hospital of Southwest Medical University from 1999 to 2021 were reviewed.Results:There were 99 males (70.2%) and 42 females (29.8%). The average age of the patients was (63.75±13.16) years; 127 patients (90.1%) complained abdominal pain.The number of all-cause deaths in the perioperative period was 27 (19.1%). ROC curve analysis showed that the optimal cutoff value of the age with predictive value was 64.5 years. The results of multivariate COX regression analysis showed that age ≥65 years old ( HR=3.855, 95% CI: 1.739-8.545), neutrophil count ( HR=1.072, 95% CI: 1.018-1.130), heart failure ( HR=2.863, 95% CI: 1.332-6.154), creatinine ( HR=1.009, 95% CI: 1.003-1.015), D-Dimer ( HR=1.112, 95% CI: 1.025-1.205) was an independent risk factor for all-cause death from superior mesenteric artery ischemic disease. Long-term survival rate of SMAD group was significantly higher than that of other SMAID; By comparing the clinical characteristics of different SMAID, neutrophil count, neutrophil ratio, D-dimer of SMAE group and SMAT group were significantly higher than that of SMAD group and ASSMA group. Conclusions:SMAID usually occurs in elderly men over 65 years old, with abdominal pain as the main symptom and often accompanied by hypertension. Risk factors included age, increased WBC count and D-dimer; The neutrophil count, neutrophil ratio, D-dimer in SMAE and SMAT group were significantly higher than that of SMAD and ASSMA group.

Screening methods of SARS-CoV-2 main protease inhibitors and current applications / 药学学报

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.

Effect of self-efficacy-based intelligent walking training on function of lower extremities of stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effect of self-efficacy-based intelligent walking training on function of lower extremities of stroke patients. MethodsFrom December, 2021 to December, 2022, 44 stroke inpatients from Zhejiang Provincial People's Hospital were randomly divided into control group (n = 22) and experimental group (n = 22). Both groups accepted routine rehabilitation, while the control group accepted routine gait training, and the experimental group accepted self-efficacy-based intelligent walking training on the gait training system (Walker View), for six weeks. They were assessed with Fugl-Meyer Assessment-Lower Extremities, 10-Meter Walk Test, Timed 'Up and Go' Test, stride length and average walking velocity, Functional Ambulation Category and General Self-Efficacy Scale before and after treatment. ResultsThree cases dropped down in the experimental group. All the indexes improved in two groups after treatment (|t| > 5.808, |Z| > 2.961, P < 0.01), and improved more in the experimental group than in the control group (|t| > 2.049, Z = -2.572, P < 0.05). ConclusionThe self-efficacy-based intelligent walking training can promote the recovery of motor function of lower extremities and walking ability in stroke patients.