Objective To explore the distribution and drug resistance changes of pathogenic bacteria in adult acute myeloid leukemia(AML)with bloodstream infection,and to analyze risk factors of death of patients.Methods Changes of detection rate of pathogenic bacteria and drug resistance rate of main pathogenic bacteria of 85 patients with AML and bloodstream infection 30 months before confirmed diagnosis(pathogenic bacteria detected from January 2017 to June 2019)and 30 months after diagnosis(from July 2019 to December 2021)were compared.According to the prognosis at 6 months after bloodstream infection,patients were divided into the death group(33 cases)and the survival group(52 cases).Logistic regression analysis was used to analyze risk factors of death in patients with AML complicated with bloodstream infection.Results A total of 98 strains of pathogenic bacteria were detected in 85 patients with AML complicated with bloodstream infection,mainly gram-negative bacteria(65/98,66.33%),followed by Gram-positive bacteria(29/98,29.59%)and fungi(4/98,4.08%).The proportion of fungi(all were candida)detected in the last 30 months was more than that in the first 30 months(P<0.05).There were no significant differences in proportions of gram-negative bacteria and gram-positive bacteria and drug resistance rates of Escherichia coli and Staphylococcus aureus between the late 30 months and the first 30 months(P>0.05).Logistic regression analysis showed that the history of antibiotic use within 1 month before confirmed diagnosis and septic shock were independent risk factors for death in patients with AML complicated with bloodstream infection(P<0.05).Conclusion The main pathogens of adults with AML combined with bloodstream infection are gram-negative bacteria.However,candida infection rate has increased in recent years,and patients with antibiotic use before bloodstream infection and complicated with septic shock are prone to poor prognosis.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Objective To evaluate the efficacy of different interventions to the extra cranial lesions in acute ischemic stroke(AIS)due to anterior tandem lesions(TL)on reperfusion.Methods As a multi-center,cross-sectional study,AIS due to anterior TL receiving mechanical thrombectomy(MT)were retrospectively collected.Interventions to the extra-cranial stenosis were recorded.Post-procedural reperfusion was assessed using the modified thrombolysis in cerebral infarction(mTICI)score.Complete revascularization was defined as mTICI 3 and good revascularization was defined as mTICI 2b/3.The relationship between different extra-cranial intervention regi-mens and rate of re-vascularization was compared.Results Totally 117 patients were included with 92.3% reaching good recanalization and 63.2% reaching complete re-canalization.There was no significant difference in good re-canalization rates among various extra-cranial intervention regimens.The rate of complete re-canalization was significantly higher in patients receiving endovascular therapy(P＜0.05)and there was significant difference among various endovascular treatment regimens(P＜0.01):acute balloon angioplasty only group presented the highest rate of complete re-canalization(100.0% ),followed by acute stenting only group(80% ),acute stenting+balloon angioplasty group(73.7% )and conservative treatment group(54.3% ).Conclusions Endovascular inter-vention to extra-cranial stenosis contributes to complete re-canalization in AIS due to anterior TL receiving MT,and acute balloon angioplasty seems to be quite effective than acute stenting.

ObjectiveTo investigate the anti-inflammatory effect of the component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on the rat model of rheumatoid arthritis （RA） and the mechanism. MethodSeventy-two SPF-grade SD rats （male and female） aged 5 to 6 weeks were selected. Except the blank group， the rat model of collagen-induced arthritis （CIA） was replicated by the type Ⅱ collagen induction method. The 64 rats after successfully modeling were randomly divided into model group， methotrexate group （0.375 mg·kg^-1）， gentianoside with magnoflorine group （150.454 1 mg·kg^-1+5.061 8 mg·kg^-1）， gentianoside with clematichinenoside AR group （150.454 1 mg·kg^-1+16.433 1 mg·kg^-1）， sweroside with magnoflorine group （3.455 8 mg·kg^-1+5.061 8 mg·kg^-1）， sweroside with clematichinenoside AR group （3.455 8 mg·kg^-1+16.433 1 mg·kg^-1）， swertiamarin with magnoflorine group （9.303 2 mg·kg^-1+5.061 8 mg·kg^-1）， and swertiamarin with clematichinenoside AR group （9.303 2 mg·kg^-1+16.433 1 mg·kg^-1）， with 8 rats in each group. Each group was given the corresponding medicinal solution or normal saline by gavage for 15 d. During the experiment， the general status， of rats in each group were observed and recorded. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， rheumatoid factor （RF）， C reactive protein （CRP）， prostaglandin E₂ （PGE₂）， and anti-cyclic peptide containing citrulline antibody （anti-CCP Ab） in the serum of rats were measured by enzyme-linked immunosorbent assay （ELISA）. The histopathological changes in rat ankle joints were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression of nuclear factor-κB （NF-κB） and vascular endothelial growth factor （VEGF） in rat ankle joints. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NF-κB and VEGF in rat ankle joints. ResultCompared with those in the blank group， rats in the model group were in poor general conditions with significant foot-plantar swelling， and the content of CRP， anti-CCP Ab， and IL-1β in the rat serum was significantly increased （P<0.01）. In the model group， the tissue structure of the ankle joint was severely damaged， and the protein and mRNA expression of NF-κB and VEGF in the rat ankle joints were significantly up-regulated （P<0.01）. As compared with the model group， the general status of rats in each administration group was significantly improved. The levels of serum TNF-α， IL-1β， RF， CRP， PGE₂， and anti-CCP Ab were reduced to different degrees in these administration groups， among which the effects of the gentianoside with clematichinenoside AR group on down-regulating serum TNF-α and IL-1β， the gentianoside with magnoflorine group on down-regulating serum RF and CRP， the sweroside with magnoflorine group on down-regulating serum PGE₂， and the swertiamarin with clematichinenoside AR group on lowering serum anti-CCP Ab were better than those of administration groups. The histopathological changes in the ankle joint were improved to different degrees. The protein and mRNA expression of NF-κB and VEGF in rat ankle joints in the administration groups was significantly down-regulated （P<0.05， P<0.01）， and the swertiamarin paired with clematichinenoside AR group had the most significant effect. ConclusionThe component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma exerts a good therapeutic effect on the rat model of RA， and the compatibility of components from the two medicines has a multi-channel， multi-target， and synergistic effect. The five component compatibility patterns， namely gentiobioside with magnoflorine， gentiobioside with clematichinenoside AR， sweroside with clematichinenoside AR， swertiamarin with magnoflorine， and swertiamarin with clematichinenoside AR， all have potential advantages. The mechanism may be related to the reduction of inflammatory factor secretion and the inhibition of abnormal protein and mRNA expression of NF-κB and VEGF.

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB₁R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB₁Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB₁R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB₁R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB₁R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB₁R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB₁Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB₁Rs in the amygdala of NHPs.
Animals ; Callithrix ; Receptors, Cannabinoid ; Anxiety ; Amygdala ; Cannabinoids ; Phenotype

The clinical data of 6 acute promyelocytic leukemia (APL) patients with thrombosis as the first manifestation were retrospectively analyzed. Among 6 patients, 5 were males and 1 female.The median age at diagnosis was 55 years old. All patients had risk factors for cardiovascular disease (CVD), and 5 patients met the diagnostic criteria for disseminated intravascular coagulation (DIC). There were 3 patients at low risk (bcr1 subtype), 1 at intermediate risk (bcr2 subtype) and 2 at high risk (1 bcr3 subtype and 1 unknown). FLT3-ITD mutations were tested in 3 cases, all of whom showed negative results. Arterial thrombosis was found in all 6 cases, 4 cases had cerebral infarction, 1 had lower limb arterial embolism, and 1 had multiple arterial and venous thrombosis. Four patients with cerebral infarction received all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO)±chemotherapy and symptomatic treatment (1 patient at high risk did not receive ATRA), 2 patients achieved complete remission (CR), and the other 2 patients died of cerebral hemorrhage and cerebral infarction, respectively. One patient with lower extremity arterial thrombosis died suddenly within 12 h after admission likely due to acute myocardial infarction. One patient with mixed thrombosis received low molecular weight heparin and rivaroxaban successively after inferior vena cava filter implantation, and achieved CR after ATRA+ATO treatment. Thrombosis is a less common and under-recognized presentation in APL.Thrombosis patients with blood cells and/or coagulation abnormalities should consider the possibility of APL. APL patients complicated with thrombosis have a high probability of DIC and remain mostly intractable to existing treatments, who are at high risk of death and poor prognosis.

OBJECTIVE To investigate the mecha-nism of endoplasmic reticulum stress in cerebral isch-emic stroke from a theoretical perspective based on net-work pharmacology.METHODS GeneCards and OMIM databases were used to screen out the related targets of cerebral ischemic stroke and endoplasmic reticulum stress.And Venny2.1.0 was used to draw Venn's diagram to get the intersecting genes between cerebral ischemic stroke and endoplasmic reticulum stress.String data-base was used to get the protein-protein interaction(PPI)diagram and cytoscape was used for visualization analy-sis.The key genes were screened out by cytohubba plug-in,and enrichment analysis was performed.RESULTS Network pharmacology showed that there were 3744 cerebral ischemic stroke-related targets and 8675 endo-plasmic reticulum stress-related targets.After screening,41 common targets were got.There were 37 nodes,390 edges in the PPI network,namely,there were 37 interact-ing proteins and 390 interacting relationships.The key genes identified by cytohubba plug-in were IL-6,ALB,INS,TNF,AKT1,CASP3,MAPK3,TP53,SIRT1 and VEGF.The biological process involves reaction to oxida-tive stress,the regulation of neuron death,and negative regulation of cell differentiation,etc.;cellular components were related to the membrane raft,smooth endoplasmic reticulum,endoplasmic reticulum lumen and other com-ponents;molecular function aspects were related to sig-naling receptor activator activity,chaperone binding and protease binding.Enrichment analysis of pathway revealed that the intersecting targets were involved in PI3K/Akt pathway and protein processing in endoplasmic reticulum,etc.CONCLUSION The endoplasmic reticu-lum stress in cerebral ischemic stroke is related to the bi-ological processes of reaction to oxidative stress,the reg-ulation of neuron death,and negative regulation of cell differentiation,the mechanism may be related to neuroin-flammation and apoptosis.

Objective:To explore any effect of transcranial direct current stimulation (tDCS) on neurons, behavior, cerebral blood flow (CBF), vascular regeneration, and the expression of vascular endothelial growth factor (VEGF) and CD34 protein in rats modeling cerebral infarction.Methods:Thirty-two adult male Sprague-Dawley rats were randomly divided into a sham surgery group (Sham group), a model group (modeled with middle cerebral artery occlusion, MCAO group), an anode transcranial direct current stimulation group (A-tDCS group), and a cathode transcranial direct current stimulation group (C-tDCS group), each of 8. MCAO models were established in the rats of the MCAO, A-tDCS and C-tDCS groups using thread fixation. Twenty-four hours after successful modeling, both the Sham and MCAO groups were connected with electrodes without current stimulation, while the A-tDCS and C-tDCS groups were given 20 minutes of 200μA anodic or cathodic electrical stimulation daily, 5 days a week for 12 days. Before and 24 hours after the modeling, and then after the 12 days of treatment, the four groups received Longa neurobehavioral scoring. Moreover, three days after the modeling as well as after the 12 days of treatment, changes in CBF were observed using MRI. Any blood vessel regeneration was observed using immunofluorescence methods, and the expression of VEGF and CD34 proteins were detected using western blotting.Results:The rats in the MCAO, A-tDCS and C-tDCS groups exhibited various degrees of neurological deficit after the modeling. After the 12 days of treatment the average neurobehavioral scores of the A-tDCS and C-tDCS groups were significantly lower than that of the MCAO group, with the A-tDCS group′s average significantly lower than that of the C-tDCS group. Three days after the modeling, 3D-arterial spin labeling scanning showed a significant decrease in CBF around the ischemic lesion in the MCAO, A-tDCS and C-tDCS groups, but that had increased to varying degrees after 12 days of treatment. The changes in the A-tDCS and C-tDCS groups were significantly larger than in the MCAO group on average, with the former group improving significantly more than the latter. After the 12 days of treatment, new vascularization and the expression of VEGF and CD34 proteins were significantly higher in the A-tDCS and C-tDCS groups than in the MCAO group, with the change in the former group again significantly greater than in the latter.Conclusions:tDCS can relieve the symptoms of neurological deficits in rats with cerebral infarction, promote vascular regeneration, CBF, and expression of VEGF and CD34 proteins. Anodic is superior to cathodic stimulation.

Objective: To analyze the epidemiology and spatial-temporal distribution characteristics of hand, foot and mouth disease (HFMD) in Shanxi province. Methods: The data of HFMD in Shanxi province from 2009 to 2020 were collected from notifiable disease management information system of Chinese information system for disease control and prevention and analyzed by descriptive epidemiology, Joinpoint regression, spatial autocorrelation analysis and spatio- temporal scanning analysis. Results: A total of 293 477 HFMD cases were reported in Shanxi province from 2009 to 2020, with an average annual incidence of 67.64/100 000 (293 477/433 867 454), severe disease rate of 5.36/100 000 (2 326/433 867 454), severe disease ratio of 0.79%(2 326/293 477), mortality of 0.015/100 000 (66/433 867 454), and fatality rate of 22.49/100 000 (66/293 477). The reported incidence rate, severe disease rate, mortality rate and fatality rate of HFMD showed decreasing trends. The main high-risk groups were scattered children and kindergarten children aged 0-5. The incidence of HFMD had obvious seasonal variation, with two peaks every year: the main peak was during June-July, the secondary peak was during September-October and the peak period is from April to November. A total of 13 942 laboratory cases were confirmed, with a diagnosis rate of 4.75% (13 942/293 477), including 4 438 (35.11%, 4 438/293 477) Enterovirus A71 (EV-A71) positive cases, 4 609 (33.06%, 4 609/293 477) Coxsackievirus A16 (CV-A16) positive cases, and 4 895 (31.83%, 4 895/293 477) other enterovirus positive cases. There was a spatial positive correlation (Moran's I ranged from 0.12 to 0.58, all P<0.05) and the spatial clustering was obvious. High-risk regions were mainly distributed in Taiyuan in central Shanxi province, Linfen and Yuncheng in southern Shanxi province, and Changzhi in southeastern Shanxi province. Spatial-temporal scanning analysis revealed 1 the most likely cluster and 8 secondary likely clusters, of which the most likely cluster (RR=2.65, LLR=22 387.42, P<0.001) located in Taiyuan and Jinzhong city, Shanxi province, including 12 counties (districts), and accumulated from April 1, 2009 to November 30, 2018. Conclusions: There was obvious spatial-temporal clustering of HFMD in Shanxi province, and the epidemic situation was in decline. The key areas were the districts in urban areas and the counties adjacent to it. Meanwhile, the monitoring and classification of other enterovirus types of HFMD should be strengthened.
Child ; Humans ; Hand, Foot and Mouth Disease/epidemiology* ; Spatial Analysis ; Enterovirus Infections ; Spatio-Temporal Analysis ; Cluster Analysis

ObjectiveIn this study， the two different origins of Lycii Cortex in the 2020 edition of Chinese Pharmacopoeia were determined to analyze their chemical consistency by comparing their main chemical composition. MethodThirty representative batches of Lycii Cortex were collected， content determination and fingerprint analysis methods were established by ultra performance liquid chromatography-photodiode array detector （UPLC-PDA） combining with multivariate statistical analysis to evaluate the similarities and differences between two origins of Lycii Cortex. Respectively by the mobile phase of acetonitrile （A）-0.15% trifluoroacetic acid aqueous solution （B） and the mobile phase of acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-4 min， 5%-12%A； 4-8 min， 12%A； 8-12 min， 12%-14%A； 12-15 min， 14%-30%A； 15-17 min， 30%-40%A； 17-18 min， 40%-90%A）， and the detection wavelength was set at 280 nm. ResultThis established content determination and fingerprint methods had good precision， stability and repeatability. The similarities of 30 batches of Lycii Cortex were above 0.90 by comparing with the control fingerprint， and the eight common peaks in fingerprints of Lycii Cortex from Lycium barbarum and L. chinense were all phenolic amides， which were kukoamine B， N-（4，9，13-triazatridecan-1-yl）-3，4-dihydroxybenzenepropanamide， feruloylputrescine， N₁，N₅-bis （dihydrocaffeoyl） spermidine or N₅，N₁₀-bis （dihydrocaffeoyl） spermidine， N₅-caffeoyl-N₁₀-dihydrocaffeoylspermidine， N₅-dihydrocaffeoyl-N₁₀-caffeoylspermidine， N₁，N₅-bis （caffeoyl） spermidine and lyciumin A. Among them， the content ranges of kukoamine B in Lycii Cortex from L. chinense and L. barbarum were 1.22%-8.18%， 2.52%-12.24%， respectively. ConclusionThe established UPLC analysis method can be used for the content determination and fingerprint analysis of Lycii Cortex. This study indicates that chemical contour of Lycii Cortex from L. barbarum and L. chinense are similar， there are no significant differences in kukoamine B content， and they have consistency in the chemical composition.