High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Clinical study of drug-coated balloon in the treatment of symptomatic intracranial atherosclerotic stenosis / 中华放射学杂志

Objective:To evaluate the safety and efficacy of drug-coated balloon (DCB) in the treatment of symptomatic intracranial atherosclerotic stenosis.Methods:Forty-nine patients with symptomatic intracranial atherosclerotic stenosis treated with DCB in the People′s Hospital of Zhengzhou University from January 2018 to August 2021 were retrospectively included. The location and number of lesions were as follows: 21 cases of the middle cerebral artery, 11 cases of the intracranial segment of vertebral artery, 12 cases of the basilar artery, and 5 cases of the intracranial segment of internal carotid artery. Pre-dilatation of the lesion with a normal balloon followed by DCB angioplasty. Clinical follow-up (outpatient or telephone) was carried out at 30 days, 3 months, 6 months, and 1 year after the operation. Imaging follow-up was carried out at 6 months postoperatively. The surgical success rate (defined as the proportion of patients with residual stenosis<50% after balloon dilatation), perioperative safety (any strokes, TIA, and deaths within 1 month), stroke recurrence, and restenosis were analyzed.Results:The operation was performed in all patients successfully. The median stenosis level was 80% (75%, 85%) preoperatively and 20% (15%, 30%) at the time after the operation. The success rate of the operation was 91.8% (45/49). Stenting was given in 11 cases (22.4%, 11/49) for severe flow-limiting vascular entrapment, or non-flow-limiting entrapment, owing to the concern of subsequent progression of the entrapment. Three cases (6.1%, 3/49) had significant vascular elastic retraction and implement stent implantation. One patient (2.0%, 1/49) developed symptomatic cerebral infarction during perioperative period, and the symptoms improved after treatment. No fatal or disabling stroke occurred. All patients were followed-up successfully. The median follow-up time was 12 months. Two patients (4.1%, 2/49) had a stroke in the responsible vascular area, and 1 (2.0%, 1/49) patient had a stroke in the non-responsible vascular area. Thirty-eight patients (77.6%, 38/49) had followed-up images. The median follow-up time of postoperative imaging was 6 months. Restenosis occurred in two cases (1 case had symptomatic restenosis), and the incidence of restenosis was 5.3% (2/38).Conclusions:DCB in the treatment of symptomatic intracranial atherosclerotic stenosis has a high technical success rate, good perioperative safety, and low stroke recurrence rate in short-term follow-up, demonstrating the good feasibility, safety, and efficacy of DCB.

Surgical treatment and perioperative multidisciplinary management of neuromuscular scoliosis in children / 中国小儿急救医学

Scoliosis is a common deformity in neuromuscular disease, which usually has the characteristics of early onset age, severe degree of deformity, and rapid progression.Neuromuscular scoliosis often leads to serious damages to the quality of life, and results in the loss of walking, standing and sitting, and cardiopulmonary insufficiency.Surgical treatment can improve the quality of life for children with neuromuscular scoliosis, but surgical treatment is still challenging due to the complex surgery and many complicated diseases.The complications are much higher than those of idiopathic scoliosis.A multidisciplinary team is necessary in the surgical treatment of neuromuscular scoliosis to promptly and effectively reduce the complications.

Efficacy of polyetheretherketone rod hybrid surgery in preventing proximal junctional failure after adult spinal deformity surgery / 中华外科杂志

Objective: To investigate the clinical outcome and preventive effect of polyetheretherketone(PEEK) rod hybrid surgery on proximal junction failure(PJF) after long-segment fusion of adult spinal deformity. Methods: A retrospective study was conducted to analyze patients with degenerative scoliosis/kyphosis who underwent long-segment decompression and fusion surgery at Department of Orthopedics, Peking University First Hospital from January 2017 to December 2021. A total of 75 patients were included in the study, including 14 males and 61 females, aged (67.2±6.8)years (range:55 to 84 years). According to the operation method chosen by the patients, the patients were divided into PEEK rod hybrid group (20 cases) and traditional titanium rod group (55 cases). The general information of the patients was collected, and the coronal and sagittal parameters of the spine were measured before operation, at 1 month after operation, and at the last follow-up. The clinical effect of surgery was judged by the visual analogue scale (VAS) and Oswestry disability index (ODI). Whether proximal junctional kyphosis (PJK) and PJF occurred during the follow-up and the time of occurrence were recorded. Comparisons between groups were performed using independent sample t test, Mann-Whitney U test, χ2 test and Fisher's exact probability method. The data before and after surgery in the same group were compared using the paired sample t test and the Wilcoxon test. Results: There were no significant differences in age, gender, body mass index, bone mineral density, distal instrumented vertebrae, surgical segments, osteotomy method, operation time, and intraoperative bleeding between the two groups (all P>0.05). The follow-up time of the PEEK rod group was shorter(M(IQR)16.5(4.8) vs. 25.0(12.0),Z=-4.230,t<0.01). There were no significant differences in coronal, sagittal parameters, VAS, and ODI between the two groups before operation (all P>0.05). Postoperative coronal Cobb angle, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, sagittal vertical axis (SVA), VAS, and ODI were significantly improved in both groups(all P<0.05). At the last follow-up, the SVA of the PEEK rod hybrid group was(3.74±2.40)cm, which was significantly lower than that of the titanium rod group (6.28±4.06)cm (t'=-3.318, P=0.002). At the last follow-up, the ODI of the PEEK rod hybrid group was 30.7±6.1, significantly better than the titanium rod group 39.3±17.2. PJK occurred in 2 patients (10.0%) in the PEEK rod hybrid group, and no PJF phenomenon was observed. In the titanium rod group, 18 patients (32.7%) developed PJK, and 11 patients (20.0%) developed PJF. There was a statistically significant difference in the incidence of PJF between the PEEK rod hybrid group and the titanium rod group (P=0.031). Conclusions: PEEK rod hybrid surgery can achieve good clinical results in the treatment of adult spinal deformities. Compared with traditional titanium rod surgery, it can significantly reduce the incidence of postoperative PJF and improve the clinical function of patients.

Research progress on multi-target regulation strategies of tumor microenvironment based on nano-drug delivery system / 药学学报

Tumor microenvironment (TME) is composed of endothelial cells, pericytes, immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), extracellular matrix (ECM) and other components of the complex biological environment. TME interacts with the tumor cells through a large amount of signaling pathways, participates in the process of tumor progression, invasion, and metastasis. Hence, TME has become a potential therapeutic target for cancer treatment, exhibiting excellent therapeutic potential and research value in the field of cancer treatment. Currently, the novel nanotechnology has been widely applied in anticancer therapy, and nanotechnology-mediated drug delivery system is being explored to apply in TME modulation to inhibit tumor progression. Nanotechnology-mediated drug delivery has many advantages over traditional therapeutic modalities, including longer circulation times, improved bioavailability, and reduced toxicity. This review summarized the research of targeted nano-drug delivery based on TME regulation, including regulation strategies based on CSCs, CAFs, immune cells, ECM, tumor vascularization, exosomes, and microbiota. In addition, we summarized the advantages, opportunities, and challenges of TME regulation strategy compared with traditional treatment strategy, which provides a reference for the application of nano-drug delivery system based on TME regulation strategy in tumor precision therapy.

Current research in liver transplantation during the Covid-19 pandemic / 中华外科杂志

The coronavirus disease (Covid-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drastically changed our daily life and clinical practice.Due to the reduction of liver transplantation and the liver injury caused by SARS-CoV-2 infection during the pandemic,the prognosis of waitinglisted liver transplant candidates is worse.Due to the long-term immunosuppressive therapy of liver recipients,their risk of infection is higher than the general population.Although some studies suggested that immunosuppressive therapy seems to have a protective effect in infected patients,it also leads to chronic infection.Due to the concerns about the risk of virus transmission,expert consensus does not recommend the utilization of donor livers with the history of Covid-19.Currently,published articles do not support the argument that virus can be transmitted to recipients through donor livers.Therefore,the feasibility of liver transplantation utilizing donor livers with SARS-CoV-2 infection remains controversial.In this article,current advances in liver transplantation during the Covid-19 pandemic are reviewed to provide a new perspective for liver transplantation in the future.

Association of vitamin D levels with hemoglobin and serum ferritin levels among primary and middle school students / 预防医学

Objective@#To investigate vitamin D levels among primary and middle school students in Xicheng District, Beijing Municipality, and to examine the association of vitamin D levels with hemoglobin (Hb) and serum ferritin (SF) levels, so as to provide insights into the prevention of anemia among primary and middle school students. @*Methods@#The first, third and fifth grade primary school students and the first grade junior high school students were sampled from Xicheng District in 2019, using the multistage stratified cluster sampling method, and students' gender, age, height, weight and Hb levels were collected. The 25-hydroxyvitamin D [25-( OH )D] was measured using electrochemiluminescence assay, and SF was detected using immunoturbidimetry. The vitamin D deficiency was determined according to the American College of Endocrinology guidelines. The associations of 25-( OH) D levels with Hb and SF levels were examined using Pearson correlation analysis and Spearman rank correlation analysis. @*Results@#Totally 403 primary and junior high school students were investigated, including 196 boys ( 48.64% ) and 207 girls ( 51.36% ). There were 179, 114 and 110 students at ages of 6 to 8 years ( 44.41% ), 9 to 11 years ( 28.29% ) and 12 to 13 years ( 27.30% ), respectively. The mean 25-( OH )D level was ( 14.80±5.96 ) ng/mL among the study students, and there were 90 students ( 22.33% ) with severe vitamin D deficiency, 243 students ( 60.30% ) with vitamin D deficiency, 63 students ( 15.63% ) with vitamin D inadequacy and 7 students ( 1.74% ) with vitamin D sufficiency. The mean Hb level was ( 136.28±8.33 ) g/L and the median SF level (interquartile range) was 56.80 (14.36) ng/mL among the study students, respectively. The 25-( OH )D level positively correlated with Hb ( r=0.364, P<0.001 ) and SF levels ( rs=0.374, P<0.001 ), and after adjustment for age and body mass index, the 25-( OH )D still correlated positively with Hb ( r=0.157, P=0.048 ) and SF levels ( rs=0.174, P=0.022 ) .@*Conclusions@#Vitamin D deficiency is prevalent among primary and middle school students in Xicheng District, and the 25-(OH)-D levels correlate positively with Hb and SF levels. 25-( OH )-D deficiency may contribute to the development of anemia.

Drug-coated balloon in the treatment of in-stent restenosis of the vertebrobasilar artery:an application study / 中华放射学杂志

Objective:To evaluate the safety, feasibility and efficacy of drug-coated balloon (DCB) in the treatment of in-stent restenosis (ISR) of the vertebrobasilar artery.Methods:Twenty-one patients with ISR of the vertebrobasilar artery treated with DCB at the Zhengzhou University People′s Hospital from January 2018 to December 2020 were retrospectively included. There were 22 lesions with ISR, of which 8 were located in the initial segments of vertebral artery, 12 were located in the V4 segment of the vertebral artery, and 2 were located in the basilar artery. The clinical prognosis was evaluated by modified Rankin Scale (mRS), and the target vessel restenosis was evaluated by DSA, CTA or MRA. The safety, feasibility and effectiveness of DCB in the treatment of vertebrobasilar artery ISR were analyzed by perioperative complications, technical success rate and follow-up.Results:All 21 patients with ISR underwent successful interventional surgery. No stroke, TIA and death occurred in perioperative period. During the operation, two cases (9.5%) were treated with Apollo stent due to the residual stenosis>50% after DCB dilation. The technical success rate was 90.5%. The mean stenosis of the target vessel was improved immediately from preoperative (78.1±11.3)% to postoperative (22.1±8.3)%. All the 21 patients were followed up. As of the last follow-up in September 2021, the median clinical follow-up period was 19 (12, 33.5) months, and there were no stroke, TIA and death caused by the corresponding artery. The mRS score was 0 in 18 patients 1 in 2 patients and 2 in 1 patient. Imaging follow-up was available in 13 cases (61.9%) with a median follow-up time of 7(5.5, 19) months, and the target vessel restenosis rate was 7.7% (1/13).Conclusions:This preliminary study has shown that DCB in the treatment of ISR of the vertebrobasilar artery is safe and feasible, with a high technical success rate and low restenosis rate, which provides clinical application evidence, but the long-term effect needs further follow-up observation.

Study on influencing factors of plasma FDP and D-dimer levels of newborns in NICU / 国际儿科学杂志

Objective:To investigate the influencing factors of physiological and pathological conditions at birth of newborn and gestational conditions of pregnant mothers on plasma fibrin/fibrinogen degradation products(FDP)and D-dimer levels.Methods:From May 1, 2018 to October 31, 2018, 222 newborns admitted to NICU of the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were enrolled in this study.Newborns were sent to NICU within 2 hours after birth and venous blood was collected immediately.The levels of FDP and D-dimer were detected by immunoturbidimetry.Groups were divided according to different gender, gestational age, birth weight, relationship between gestational age and birth weight, mode of delivery, asphyxia at birth, acidosis, antenatal hormone use, anticoagulant drugs, and perinatal risk factors(gestational hypertension, premature rupture of membranes, abnormal placenta, gestational diabetes). The levels of plasma FDP and D-dimer were compared among the groups.Mann Whitney U test, Kruskal Wallis H test, Spearman rank correlation and generalized linear model were used for statistical analysis. Results:The plasma FDP and D-dimer values of 222 NICU neonates were skewed at birth, with median values of 6.00 mg/L and 1.74 mg/L, and quartile distances of 10.40 mg/L and 2.55 mg/L, respectively.The concentrations of FDP in neonates born to natural labour and cesarean section were 11.70 mg/L and 5.30 mg/L, respectively, and D-dimer concentrations were 2.92 mg/L and 1.52 mg/L, respectively.The FDP and D-dimer levels were significantly higher in the former(Z values were -4.006 and -4.198, respectively, P<0.05). The levels of FDP and D-dimer in newborns with different gestational age, different birth weight and different blood pH values were compared respectively, and the differences were statistically significant( χ2 values were 15.322, 18.394, 9.677, 11.492, 7.023 and 8.345, respectively, P<0.05). Further analysis showed that the levels of FDP and D-dimer in neonates with gestational age < 34 weeks were significantly higher than those in~<37 weeks group and ≥37 weeks group( P<0.05). The FDP and D-dimer levels in the birth weight<1 500 g group were significantly higher than those in~<2 500 g group and ≥2 500 g group( P<0.05). Higher FDP and D-dimer levels were found in the pH<7.20 group than in the pH ≥7.35 group( P<0.05). A generalized linear model was established for multifactor analysis.The results showed that the concentration of FDP and D-dimer in plasma was related to gestational age, birth weight and arterial pH value. Conclusion:The levels of plasma FDP and D-dimer in NICU newborns at birth were influenced by gestational age, birth weight and acid-base balance.

Analysis of pathogens distribution and risk factors of burn infections in burn patients / 中华检验医学杂志

Objective:To investigate and analyze the distribution of pathogens and to explore the related risk factors of infections in burn patients in order to provide theoretical basis for effective prevention and treatment of wound infections in burn patients.Methods:A total of 245 burn patients, admitted to the PLA 926 Hospital from January 2016 to December 2020, were selected. The pathogens and antimicrobial susceptibility of the wound secretions were tested and the clinical data of burn patients were collected. The risk factors of burn wound infection were screened by single factor comparison method and multivariate logistic regression.Results:Among the 245 burn patients, 184 patients were with bacterial infections, the infection rate was 75.10% (184/245), and 79 patients were multi-drug resistant, accounting for 42.93%(79/184). A total of 367 strains of pathogens were isolated from wound secretions in the 184 patients, among which 72 (19.62%, 72/367) strains were gram-positive bacteria, mainly Staphylococcus aureus (11.44%, 42/367), 283 (77.11%, 283/367) strains were gram-negative bacteria, mainly Pseudomonas aeruginosa (20.16%, 74/367) and Acinetobacter baumannii (19.89%, 73/367), and 12 (3.27%, 12/367) strains were fungi, mainly Aspergillus (1.91%, 7/367). The results of drug sensitivity tests showed that the pathogens of burn patients were highly resistant to common antibiotics. Monofactor analysis showed that age(χ 2=8.629, P=0.013), burn area (χ 2=21.504, P=0.002), wound depth (χ 2=17.139, P=0.000), hypovolemic shock (χ 2=21.112, P=0.000) and length of hospital stay (χ 2=21.967, P=0.000) were the related risk factors for wound infections. Multivariate logistic regression analysis showed that ages below 4 years old or over 69 years old ( OR=8.414,95% CI:2.971-23.830, P=0.000), burn area>30% ( OR=5.672,95% CI:1.029-31.272, P=0.046), Ⅲ degree wound ( OR=4.069,95% CI:1.396-11.858, P=0.010), length of hospital stay≥15 days ( OR=2.593,95% CI:1.091-6.162, P=0.031) were the independent risk factors of wound infections in burn patients. Conclusions:The incidence of wound infection and multi-drug resistance is relatively high in burn patients, and the pathogens are mainly gram-negative bacteria. Age, burn area, burn wound depth and length of hospital stay are the high-risk factors for wound infections, and taking effective preventive measures according to risk factors can reduce the occurrence of wound infections and hospital infections.

Effects of somatostatin receptor ligands on bone metabolism in acromegaly / 中华内分泌代谢杂志

Objective:To investigate the effect of somatostatin receptor ligands (SRLs) on bone metabolism in patients with acromegaly.Methods:Retrospective analysis of clinical data of acromegaly patients( n=100) received surgery or SRLs alone for 3 months. The changes of growth hormone (GH), insulin-like growth factor-1 (IGF-1), osteocalcin (OC), N-mid fragment of osteocalcin (N-MID), amino-terminal peptide of type I procollagen (P1NP) and C-terminal peptide degradation product of type I collagen(CTX) were compared before and after treatment. Patients were divided into drug treatment group and surgical group according to treatment methods. According to the decline of GH after medication, patients in the drug treatment group were further divided into drug sensitive group and drug insensitive group. Results:The average dynamic GH and IGF-1 indexes in the drug treatment group were significantly decreased after treatment compared with before treatment (both P<0.05), and CTX was also significantly decreased after treatment [1.25 (0.67, 1.40) ng/mL vs 1.34 (0.57, 1.68) ng/mL, P<0.05]. The mean dynamic GH, IGF-1 index, OC, N-MID, P1NP, and CTX in surgical group were significantly decreased after treatment compared with before treatment (all P<0.01). In the surgical group, there was a positive correlation between GH difference (ΔGH) and N-mid difference (ΔN-MID; r=0.454, P=0.026), and there was a positive correlation between IGF-1 index difference (ΔIGF-1 index) and CTX difference (ΔCTX; r=0.339, P=0.036). After treatment, the mean dynamic GH, IGF-1 index, CTX, P1NP, and N-MID in drug treatment group were significantly higher than those in surgical group (all P<0.001). CTX and N-MID decreased significantly after treatment in drug sensitive group compared with drug insensitive group (35.3% vs 7.2%, P<0.001; 24.1% vs 11.8%, P<0.05), and ΔGH was positively correlated with ΔCTX ( r=0.328, P=0.004). Conclusion:SRLs treatment can reduce bone formation marker N-MID and bone resorption marker CTX, improving the high turnover state of bone metabolism in patients with acromegaly, which may attribute to the reduction of GH and IGF-1 levels.

Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Toll-like receptor 3 (TLR3) is a member of the TLR family, mediating the transcriptional induction of type I interferons (IFNs), proinflammatory cytokines, and chemokines, thereby collectively establishing an antiviral host response. Studies have shown that unlike other TLR family members, TLR3 is the only RNA sensor that is utterly dependent on the Toll-interleukin-1 receptor (TIR)‍-domain-containing adaptor-inducing IFN-‍β (TRIF). However, the details of how the TLR3-TRIF signaling pathway works in an antiviral response and how it is regulated are unclear. In this review, we focus on recent advances in understanding the antiviral mechanism of the TRIF pathway and describe the essential characteristics of TLR3 and its antiviral effects. Advancing our understanding of TLR3 may contribute to disease diagnosis and could foster the development of novel treatments for viral diseases.

In vitro and in vivo anti-HMPV activity of JH001 isolated from Chinese medicinal herbs / 中国药理学与毒理学杂志

OBJECTIVE Human metapneumovirus (hMPV) is semblable to respiratory syncytial virus (RSV) which causes respiratory infections typically characterized by cough, runny nose, fever, and nasal congestion but sometimes progressing to bronchiolitis and pneumonia. Whereas, there is no corresponding drug to inhabit the virus. Studies of new compounds with potential anti-HMPV activity could produce clinical value. Chinese herbal medicine played a great role during COVID-19, therefore we choose some small molecular (JH001) extracted from botany to investigate therapeutic effect on hMPV and the underlying mechanisms. METHODS In this study, 16HBE cells were used as a model to explore in vitro antiviral effect. Cytotoxicity assays were performed before the antiviral tests, cell viability of 16HBE cells handled by different concentration of JH001 was estimated by Cell Counting Kit-8 (CCK-8). Then RT-qPCR, immunofluores?cence, and flow cytometer were used to test the viral titer after cells infected with hMPV. Eventually, 6-8 weeks mice were infected intranasally with 60 μL of hMPV, the control group was treated with 0.9％ saline water, other groups were administered with JH001 and ribavirin, then the lung virus titer and protective effect in lung were judged. RESULTS The obtained JH001 exhibited no cytotoxicity to 16HBE cells during 6.25 - 200 μmol · L-1. RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline. And fluo?rescence exhibited distinct decrease of hMPV-N protein, flow cytometer results showed that MFI decrease evidently. Sig?nificant reduction of N-gene expression was observed in those mice treated with JH001 compared with saline group, which indicated that JH001 probably had protective and therapeutic effect on viral replication. CONCLUSION This study illustrated that JH001 might be a promising option for small molecular against hMPV and JH001 might be worthy of fur?ther development and used as a potential therapeutic strategy for other respiratory viruses in the future.

Research Progress in Pharmacology of Xiaoyaowan / 中国实验方剂学杂志

In traditional Chinese medicine， it is believed that the spleen is the foundation of acquired nature and the source of Qi and blood. All life activities of a person since birth depend on the water and grain essence transported by spleen and stomach. The liver helps the spleen to strengthen the movement， the liver and spleen cooperate with each other. The liver and the spleen are invigorated， so that the Qi and blood are sufficient. The external energy can nourish the limbs， muscles and fur. The Qi and blood can be supplied to the internal organs， meridians and bones， and the body can be nourished both inside and outside to strengthen the acquired foundation. Emotional dissatisfaction can lead to stagnation of liver Qi， loss of spleen Qi， failure to dredge Qi， and deficiency of spleen Qi， forming the syndrome of liver depression and spleen deficiency. Its clinical manifestations include the symptoms of liver Qi stagnation such as depression， stamina， and chest fullness， as well as symptoms of spleen deficiency such as anorexia， abdominal distension， loose stools. Xiaoyaowan is an effective classic prescription for the treatment of liver stagnation and spleen deficiency syndrome， which is based on the dosage form of Xiaoyaosan in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It has the effect of relieving depression， nourishing blood and invigorating spleen. In modern research， it has been found that Xiaoyaowan has good curative effect in the treatment of endocrine diseases， liver diseases， immune diseases， and neurological diseases， etc. It was praised by the famous medical scientist YE Tian-shi in the Qing Dynasty as "the holy medicine for women"， with a wide range of significant curative effects gynecology. Progress has been also made in pharmacological research. In this article， we have searched and consulted the relevant literature reports of Xiaoyaowan in recent years， summarized the key directions of the pharmacological research literature， and proposed deficiencies to provide relevant basis for the in-depth study of Xiaoyao pill in the future.

Research progress on metabolism and efficacy of small molecular prodrug nanosystems responsive to tumor redox microenvironment / 药学学报

Compared with normal tissues and cells, the tumor microenvironment has significant differences. For example, glutathione-related metabolic enzymes and reactive oxygen species are highly expressed in different subcellular structures, resulting in an unbalanced redox state. Aiming at the specific redox state in tumor tissues and cells, a series of small molecule prodrug self-assembled nanoparticles can be designed and connected by intelligent response linkers including disulfide bonds, sulfide bonds, and selenium bonds, thioketal bonds, etc. The in vitro and in vivo efficiency and metabolic mode of these nanoparticles are related to the type of linker. This review will summarize the tumor redox microenvironment, the design of intelligent responsive small molecule prodrug nanoparticles, and the metabolic pathways of small molecule prodrug nanoparticles with different connecting linkers and their relationship with drug efficacy.

Application of a 3D printed trabecular block cage in treatment of patients with basilar invagination and atlantoaxial dislocation / 中华创伤骨科杂志

Objective:To explore the short-term outcomes of a 3D printed trabecular block cage to assist posterior internal fixation for the treatment of patients with basilar invagination and atlantoaxial dislocation.Methods:Between June 2017 and February 2019, 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial distraction and posterior internal fixation at Department of Orthopedics, The First Affiliated Hospital to Zhengzhou University. They were 5 males and 7 females, aged from 34 to 62 years (average, 45.6 years). 3D printed cages were inserted intraoperatively between the joints of the atlantoaxial lateral mass. The atlanto-dental interval interval (ADI), cervico-medullary angle (CMA) and distance from tip of the odontoid process to Chamberlain's line (DOCL) and the Japanese Orthopedic Association (JOA) scale were compared between preoperation and 12 months postoperation to observe the fusion of the joints of the atlantoaxial lateral mass.Results:Operation went on uneventfully in all the 12 patients. Operation time averaged 116.5 min (from 85 to 190 min), fluoroscopy frequency 9.4 times (from 6 to 21 times), and intraoperative bleeding 82.3 mL (from 50 to 210 mL). No such postoperative complications occurred as cerebrospinal leak, cerebral infarction, or breakage, displacement or loosening of implants. All patients were followed up for 18 to 42 months (mean, 26.3 months). Their preoperative JOA, ADI, CMA and DOCL [8.33±0.98, (8.66±1.64) mm, 119.63°±4.15° and (9.66±2.15) mm] were significantly improved to 14.17±1.03, (2.63±0.59) mm, 153.76°±7.88° and (2.07±0.69) mm ( P<0.05) at 12 months postoperation. Bony fusion was achieved in all the operative segments. Conclusion:In the treatment of patients with basilar invagination and atlantoaxial dislocation, a 3D-printed trabecular block cage can be used to assist posterior internal fixation to achieve satisfactory reduction and maintain the height of joint space, leading to satisfactory short-term outcomes.

High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M

Advances in the release mechanisms of bluetongue virus / 生物工程学报

Bluetongue virus (BTV) causes Bluetongue (BT) of ruminants vectored by culicoides midges. It is also a classic model for studying the release mechanism of non-enveloped virus. This review begins with the infection and assembly of BTV, then summarizes the advances of different ways of releasing BTV. This includes BTV-induced autophagy and the release as extracellular vesicles via multivesicular bodies, BTV-induced apoptosis and the lytic release, as well as different pathways of release through budding via plasma membrane. The regulatory mechanisms of NS3 which is a key non-structural protein during the release of BTV are also discussed, providing a basis for further understanding the molecular mechanisms underpinning the infection, proliferation and release of BTV.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.