Objective:To investigate the effects of selinexor,a inhibitor of nuclear export protein 1(XPO1)on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia(AML).Methods:MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points.The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry.Results:Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner(r24 h=0.7592,r48 h=0.9456,and r72 h=0.9425).Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner(r=0.9057 in 2.5 μmol/L group,r=0.9897 in 5 μmol/L group and r=0.9994 in 10 μmol/L group).Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner(r=0.9732),and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration.The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor.With the increase of drug concentration,the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased.Conclusion:Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation,inducing apoptosis and blocking cell cycle.

Abstract: Objective　To study severe fever with thrombocytopenia syndrome virus (SFTSV) in tick samples from different species and genera in Suizhou City, Hubei Province, China, and to explore the phylogenetic relationship between ticks and patients sources of viruses at the molecular evolutionary level. Methods In 2016 and 2017, over a continuous two-year period, 1 158 ticks were collected from Suizhou, Hubei, and their species and genera were identified. Meanwhile, 86 serum samples were collected to detect SFTSV RNA by real-time quantitative reverse transcription-PCR. All viral RNA-positive supernatants of tick homogenates were inoculated into Vero cells for viral isolation, and full genome sequencing of isolated strains was conducted. Phylogenetic tree research on SFTSV strains from ticks and cases was performed using the bootstrapped maximum-likelihood (1 000 iterations) method with Molecular Evolutionary Genetics Analysis (MEGA) software, ver. 11.0 to provide confidence estimates. Results Haemaphysalis longicornis, Ixodes sinensis, and Rhipicephalus microplus were the dominant species (95.34%) in Suizhou City, Hubei Province, China. Tick samples were pooled according to their species and developmental stage, yielding 832 pools, of which 4 were positive for SFTSV by qRT-PCR. The overall minimum infection rate (MIR) in the region was 0.35%. One SFTSV strain named HB 2016-P35, was successfully isolated from Haemaphysalis longicornis and demonstrated high homology to 16 previously reported patient-derived viruses in Hubei Province, especially to the human strain HB 2017-49 from the same region, with a genome similarity of 99.9%. In addition, the molecular phylogenetic analysis revealed five distinct SFTSV genotypes in Hubei, covering almost all currently known SFTSV genotypes. Conclusions Some areas of Suizhou City, Hubei Province, demonstrate a relatively low level of SFTSV carrying and transmission by ticks. The new SFTSV strain isolated from ticks exhibits similar genotype characteristics and high sequence homology with viruses carried by cases in surrounding cases. The study suggests that tick-to-human transmission is most likely the pathway for human infection with SFTSV, highlighting the need for continual and long-term monitoring of tick carriage of SFTSV in endemic areas.

OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar-get profiles of the components of BZBS were pre-dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich-ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further-more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec-tion analysis.Two Alzheimer's disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre-liminarily verify the anti-AD efficacy and mecha-nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat-ment of AD.In vitro experiments showed that BZ-BS could significantly reduce the release of TNF-α and IL-6 and the expression of COX-2 and PSEN1 in A β 25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of A β 25-35 induced SH-SY5Y cells,significantly increased mitochon-drial membrane potential,reduced the expres-sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU-SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu-lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further-more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun-dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

OBJECTIVE To explore the key mechanism of Bazi Bushen capsule(BZBS)in delaying the senescence of mesenchymal stem cells(MSCs)through network pharmacology and in vitro experiments.METHODS Network phar-macology was used to predict the mechanism targets of BZBS in delaying MSCs senescence.A MSCs senescence model induced by D-galac-tose(D-gal)was used to investigate the effect and mechanism of BZBS on MSCs senescence in vitro.RESULTS Network pharmacology analy-sis showed that BZSB could delay MSCs senes-cence.The experiment showed that BZBS could significantly improve the survival activity of the aged MSCs.It significantly reduced the positive rate of β-galactosidase staining and p16,p21 expression in aged MSCs,enhanced the ability of adipogenic differentiation and osteogenic differ-entiation,and increased expression of Nanog,OCT4 and SOX2 in senescent MSCs.CONCLU-SIONS Network pharmacology and in vitro cell experiments verified that BZBS could delay MSCs senescence.

Objective:To isolate and culture WU polyomavirus (WUPyV), and to analyze the genome-wide evolutionary patterns, homology and population dynamics.Methods:Real-time quantitative PCR was used to detect the nasopharyngeal aspirate samples of hospitalized children with respiratory tract infection in Beijing Friendship Hospital during 2020 to 2022. Primary human airway epithelial cells cultured at the air-liquid interface were used to isolate and culture WUPyV. Whole genome sequence of the isolated strain was obtained by Sanger sequencing. For phylogenetic and evolutionary dynamics analysis, the whole genome was compared with the published whole genome sequences in GenBank database.Results:The detection rate of WUPyV was 4.7% (31/659) during 2020 to 2022, and a clinical strain BJ0593 of WUPyV type Ⅲc was successfully isolated. The homology of the whole genome and gene fragments of WUPyV was high. The average evolutionary rate of VP2 gene was about 1.256×10 -4 substitution/site every year, and the population dynamics of WUPyV tended to be flat in the last decade. Conclusions:This study successfully isolated a clinical WUPyV type Ⅲ strain for the first time, which provided the basis for further investigation on the molecular evolution and pathogenicity of WUPyV.

Panax notoginseng contains triterpene saponins, flavonoids, amino acids, polysaccharides, volatile oil and other active components, which have the effects of promoting blood circulation, stopping bleeding, removing blood stasis, etc. This study summarized the herbal research, chemical constituents and main pharmacological activities of P. notoginseng, and based on the theory of Q-markers of traditional Chinese medicine, predicted and analyzed the Q-markers of P. notoginseng from the aspects of plant kinship, efficacy, drug properties, measurability of chemical components, etc. It was found that ginsenosides Rg_1, Re, and Rb_1 with specific content ratio, ginsenosides Rb_2, Rb_3, Rc, Rd, Rh_2, and Rg_3, notoginseng R_1, dencichine and quercetin could be used as potential Q-markers of P. notoginseng, which facilitated the formulation of quality standards reflecting the efficacy of P. notoginseng.
Panax notoginseng/chemistry* ; Ginsenosides/analysis* ; Saponins/analysis* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Panax/chemistry*

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.
Animals ; Chlorocebus aethiops ; Drugs, Chinese Herbal/pharmacology* ; Enterovirus A, Human/physiology* ; Hand, Foot and Mouth Disease ; Vero Cells

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G^-) bacteria (62.8%), 40 Gram-positive (G⁺) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G⁺ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;
Bacteremia/epidemiology* ; Bacteria ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; Sepsis

Objective:To investigate the role of TiRobot combined with O-arm assisted closed reduction and percutaneous screw fixation in unstable pelvic fracture surgery.Methods:Twelve patients with unstable pelvic fractures, 7 males and 5 females, aged 39.41±12.56 years (range 25-60 years), admitted from January 2020 to January 2021, were retrospectively analyzed. The duration between injury and surgery was 9.67±5.81 d (range 4-24 d). The following are the causes of injury, namely traffic injury in 6 cases, fall from height injury in 4 cases, crush injury in 2 cases. Tile type of pelvic fractures were 3 cases of type B (2 cases of type B2, 1 case of type B3), 9 cases of type C (4 cases of type C1, 3 cases of type C2, 2 cases of type C3). Sacral fractures with Denis division were 5 cases of zone I, 7 cases of zone II. Seven patients were repositioned by intraoperative traction on the injured side of the limb and maintained by fixation with a Starr frame. Two cases were repositioned by intraoperative longitudinal bone traction on each lower limb for fracture displacement. The other 3 B-type fractures were repositioned by inserting Schanz nails into the anterior inferior iliac spine bilaterally. Then, the fractures were maintained with external pelvic fixators. The fractures were assessed by O-arm fluoroscopy. Hollow screws were placed with the aid of orthopedic robotic guidance, and the screw positions were verified by O-arm fluoroscopy again after the nail placement. The duration of each screw placement and operation were recorded. The quality of fracture repositioning, hip function and postoperative complications were observed at the follow-up.Results:All patients were followed up for 8.17±1.99 months (range, 6-12 months). There were 27 screws inserted in 12 patients, with a single screw insertion duration of 19.9±1.8 min (range, 9-31 min). In all patients, one O-arm fluoroscopy was performed in each row after closed reduction and after completion of nail placement. The operative duration was 257.78±80.63 min (range, 160-450 min). The O-arm fluoroscopy after nail placement verified that 23 screws were placed in a satisfactory position at one time, with satisfactory rate of 85% (23/27) for the first nail placement. Two patients with preoperative grade II sacral plexus nerve injury recovered to grade I in one case and grade II in one case. However, the numbness was reduced after operation. No further aggravation of nerve injury occurred after surgery. The quality of fracture repositioning was evaluated according to the Matta score, including excellent in 9 cases, good in 2 cases, and acceptable in 1 case, with an excellent rate of 92% (11/12). At the last follow-up, the Majeed pelvic fracture quantitative assessment system scored 85.75±5.82 (range, 74-96). There were 8 cases in excellent and 4 cases in good. Twelve patients had one-stage wound healing. No complications, such as incision infection, nerve injury, loosening and breaking of the internal fixation occurred during the follow-up.Conclusion:TiRobot combined with O-arm assisted closed reduction and percutaneous screw fixation for unstable pelvic fractures has some advantages, including safety, precision, convenient nail placement, and less fluoroscopic radiation.

Objective:To investigate the typing and clinical value of posterior group renal calyces.Methods:From April 2020 to June 2021, 640 patients (320 men and 320 women) who underwent CTU examination in our hospital with kidneys on both sides and normal or only mild hydronephrosis in the collecting system were analyzed. A total of 1 280 renal CTU three-dimensional reconstructed images were counted.The patients aged 52.4±11.9 years. The patients' CTU images were reconstructed in three dimensions using the spine as a marker to rotate the collecting system images in stereoscopic space to simulate a prone position. A two-person review was taken to observe the imaging morphology of the renal calyces in the prone position, and the 640 renal calyces in the posterior group of the left and right sides were counted for staging. Based on the morphology of the renal calyces and the influence on the establishment of surgical access, the posterior group of renal calyces was divided into 3 major types. Pot-belly type: the renal pelvis is shaped like a pot-belly, and the renal pelvis is directly connected to the cup-shaped minor calyces without a distinct major renal calyces. Classically branched: 2 or more major renal calyces are branched and converge to form the renal pelvis. Elongated branched: the major calyces are branched, with at least one major calyces having an axis length ≥0.9cm and a neck width ≤0.3cm.The classic branching type is divided into three types, a, b, and c, including seven subtypes, based on the relationship of the posterior group of the minor calyces to the major calyces. Type a is derived from group 1 major calyces only, type b is derived from group 2 major calyces at the same time, and type c is derived from the upper, middle and lower groups of major calyces at the same time. Type a contains 3 subtypes.Type a1 is derived from the upper group of major calyces only, type a2 is derived from the middle group of major calyces only, and type a3 is derived from the lower group of major calyces only. Type b is also divided into 3 subtypes. Type b1 is derived from the upper and middle groups of major calyces at the same time, type b2 is derived from the middle and lower groups of major calyces at the same time, and type b3 for the upper and lower renal major calyces. Type c had no corresponding subtype.Results:Statistical findings revealed that all kidneys had posterior group calyces. The morphological typing of the posterior group of calyces was 8.83% (113/1 280) for the pot-bellied type, which had the highest occurrence of 2 minor calyces (5.63%, 72/1 280). 71.25% (912/1 280) had the classically branched type, which had the highest occurrence of 3 minor calyces (31.17%, 399/1 280). 19.92% (255/1 280) had the elongated branched type, with the highest percentage of 3 occurring in the calyces (9.92%, 127/1 280). The anatomical typing of the classical branching type occurred in 20.50% (187/912) for type a, 66.45% (606/912) for type b, and 13.05% (119 /912) for type c. The percentage of occurrence of type a1/a2/a3 was 4.06% (37/ 912), 6.14% (56/ 912), and 10.31% (94/912). b1/b2/b3 types occurred in 2.03% (21/912), 7.46% (68/912), and 56.69% (517/912), respectively.Conclusions:The posterior group of calyces is structurally complex and extremely variable. In this study, the posterior group calyces were found to be present in all patients, and the posterior group calyces were morphologically divided into 3 types, with the highest percentage of occurrence of the classical branching type and the highest percentage of 3 posterior group minor calyces. The classical branching anatomical typing was highest in type b with the highest percentage of type b3, which combined with stone distribution, made it easy to choose the puncture location. The typing of the posterior group of calyces can provide an anatomical basis for PCNL puncture from the posterior group.