Objective:To investigate the mechanism of IL-6 affecting the expression of CD73 on human placenta-derived mesenchymal stem cells (hPMSCs) and regulating their migration, adhesion and proliferation.Methods:Flow cytometry (FCM) and Western blot were used to analyze the effects of exogenous IL-6 or IL-6 secreted by hPMSCs on the expression of CD73 on hPMSCs. The influence of IL-6 on the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in hPMSCs was detected by monoclonal antibody blocking test and Western blot. Real-time cellular analysis (RTCA) was used to analyze the changes in the migration, adhesion and proliferation of hPMSCs after knockdown of CD73 expression or APCP pretreatment.Results:FCM and Western blot showed that both exogenous and autocrine IL-6 from hPMSCs promoted the expression of CD73 on hPMSCs ( P<0.001, P<0.01). Moreover, CD73 expression decreased significantly with the presence of IL-6R inhibitor ( P<0.01). IL-6 could up-regulate the levels of both p-STAT3 and CD73 in hPMSCs ( P<0.05, P<0.01), while CD73 expression decreased after adding STAT3 inhibitor ( P<0.01). RTCA showed that knockdown of CD73 expression on hPMSCs significantly inhibited the adhesion and proliferation ability of hPMSCs( P<0.01, P<0.05), but promoted the migration ability of hPMSCs ( P<0.05). Similarly, inhibiting the hydrolase activity of CD73 on hPMSCs by APCP also resulted in a significant decrease in the adhesion and proliferation capacities of hPMSCs, and an increase in the migration capacity of hPMSCs ( P<0.05). Conclusions:IL-6 enhanced the expression of CD73 on hPMSCs via the JAK/STAT3 pathway, thus affecting the migration, adhesion and proliferation of hPMSCs.

Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.

Objective To explore the application of the awake anesthesia and intra-operative cortico-subcortical electro-stimulation in the surgery for patients with lesions in eloquent areas.Methods Retrospective analysis of 10 patients with lesions in eloquent area,admitted to our hospital from May 2011 to December 2013,was performed.Neuroimaging was used to assess the location of the lesions before surgery,neuron-navigation was used in the craniotomy,awake anesthesia and intra-operative cortico-subcortical electro-stimulation in the surgery of lesions in eloquent areas was performed; and then,total excision of the lesions was adopted.Results Specific motor response was monitored in all the 10 patients accepted cortico-subcortical electro-stimulation,which was matched with that from anterior central gyrus; 5 of them also performed electrophotoluminescence in the language area could be detected with positive reactions.In all 10 patients,total resection was achieved in 8 and subtotal excision in 2.Two patients had transient language dysfunction after operation and got improvement within one week,and recovered to the normal state in three weeks.Myodynamia transitorily decreased in 3 patients after operation and started recovery in one week and achieved the normal state in three month.Perpetual aphasis was noted in all the patients.Conclusion Awake anesthesia and intraoperative direct electrical stimulation were helpful to distinguish lesions from eloquent area,which is a reliable,precise,and safe eloquent area location method; maximum resection of the lesions and minimal damage to the eloquent area can be achieved and the life quality of patients can be improved.

Objective:To investigate the mechanism of human placenta derived mesenchymal stem cells (hPMSCs) in the inhibition of TNF-α secretion in CD4 + IFN-γ + T cells (Th1) through CD73/nuclear factor-erythroid 2-related factor 2(Nrf2) pathway to reduce liver injury in mice with graft versus-host disease (GVHD). Methods:Flow cytometry (FCM) was used to analyze the expression of TNF-α in Th1 cells and the expression of PD-1 on CD4 + IFN-γ + TNF-α + T cells (TNF-α + Th1 cells) isolated from peripheral blood and liver tissues of mice with GVHD. Hematoxylin-hosin (HE) staining, Masson staining and immunofluorescence staining were used to observe the pathological changes in liver tissues of GVHD mice in each group. HE staining was also used to observe the pathological changes in skin and lung tissues of GVHD mice. A nonconditional protocol to induce the differentiation of peripheral blood mononuclear cells (PBMCs) into Th1 cells in vitro was established. The proportion of TNF-α + Th1 cells and the mean fluorescence intensity (MFI) of Nrf2 and phosphorylated nuclear factor-kappa B (p-NF-κB) in this T cell subgroup were detected. Results:Compared with the normal control group, the proportion of TNF-α + Th1 cells and the expression of PD-1 on this T cells in peripheral blood and liver tissues of mice in the GVHD high group increased significantly ( P<0.01). The proportion of TNF-α + Th1 cells in peripheral blood and liver tissues decreased after hPMSCs treatment ( P<0.001), but the expression of PD-1 on this T cell subset was promoted in peripheral blood and liver tissues ( P<0.01, P<0.001). However, the intervention effects of shCD73 on TNF-α + Th1 cells in peripheral blood and liver tissues were significantly weakened ( P<0.05, P<0.01). Liver histopathological analysis showed that the proportion of TNF-α + Th1 cells in liver was positively correlated with Suzuki′s score, collagen area and the MFI of α-SMA ( P<0.001). Similarly, histopathological analysis of skin and lung tissues also showed that the proportion of TNF-α + Th1 cells in peripheral blood was positively correlated with skin Marina score and lung Shukai Qiao score ( P<0.001). In vitro experiment also showed that hPMSCs down-regulated the proportion of TNF-α + Th1 cells ( P<0.01) and up-regulated the expression of PD-1 on them ( P<0.05). Further analysis showed that hPMSCs could enhance the MFI of Nrf2 ( P<0.05) and weaken the MFI of p-NF-κB ( P<0.01) in TNF-α + Th1 cells. Conclusions:hPMSCs could up-regulate the expression of PD-1 through CD73/Nrf2 pathway to inhibit the formation of TNF-α + Th1 cells, thereby alleviating liver injury in GVHD mice.

Objective To investigate the efficacy of low-dose aspirin in combination with low-molecular-weight heparin calcium for the prevention of preeclampsia,as well as its impact on hemorheological status and maternal-infant outcomes.Methods A retro-spective review was conducted on data from 367 pregnant women identified with risk factors for preeclampsia,who were examined in the Obstetrics Department of the First Affiliated Hospital of Hebei North University from June 2018 to December 2021.Participants were cate-gorized into three groups based on the preventive medication regimen they received:Group A(low-dose aspirin,n=137),Group B(low-molecular-weight heparin calcium,n=107),and Group C(combination of low-dose aspirin and low-molecular-weight hep-arin calcium,n=123).The study compared coagulation function parameters[prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer(DD)and fibrinogen(FIB)],hemorheological measures(whole blood viscosity,plasma viscosity,hemato-crit),and adverse drug reactions before and after the administration of medication.Follow-up continued until delivery to document pla-cental indicators[vascular endothelial growth factor(VEGF),microvessel density(MVD)],and maternal-infant outcomes.Results After treatment,the DD,FIB,whole blood viscosity,plasma viscosity,hematocrit and the incidence rate of premature birth in group C were lower than those in groups A and group B while the positive expression rate of VEGF,MVD,PT,APTT and Apgar score were higher than those in group A and group B(all P＜0.05).There were no statistical differences in the coagulation function,hemorheology and placental indicators between group A and group B as well as the incidence rates of eclampsia,cesarean section,postpartum hemorrhage and stillbirth and incidence rates of adverse drug reactions among the three groups(all P＞0.05).Conclusion Both low-dose aspirin and low-molecular-weight hep-arin calcium can play a preventive role in preeclampsia,and can improve the coagulation function,hemorheology and placental indicators.The combination of the two drugs has a better preventive effect and does not significantly increase the risk of medication.

Objective:To identify and characterize one Yokenella regensburgei strain(designated as CXLZQ123) isolated from a case of perionychial abscess. Methods:Strain CXLZQ123 was isolated from a patient with periungual abscess at the Dermatology Department of San County Central Hospital in June 2, 2023. The strain was initially identified through morphological and biochemical tests, followed by mass spectrometry identification, 16S rRNA sequencing and whole-genome sequencing. MEGA 11.0 was used to compare and analyze the strain′s genetic relationship with relevant species in GenBank, and a phylogenetic tree was constructed based on genetic distance to analyze its genetic evolution. Meanwhile, the average nucleotide identity between its genome and similar strains were compared.Results:The strain was identified as a Gram-negative rod. MicroScan WalkAway biochemical tests indicated that the strain was either Yokenella regensburgei (91.47%) or Hafnia alvei (8.53%). MALDI-TOF mass spectrometry confirmed it as Yokenella regensburgei. Based on 16S rRNA gene sequence analysis, the strain showed the highest similarity(99.37%) to CIP 105435 (sequence number NR_104934.1). The 16S rRNA gene sequence of the isolated strain Yokenella regensburgei was submitted to the National Center for Biotechnology Information (NCBI) with the GenBank sequence number of OR230248.1. The whole-genome of CXLZQ123 were sequenced and uploaded (NCBI, SRA sequence number: SRR26510420). The average nucleotide identity between CXLZQ123 and Yokenella regensburgei strains W13 and UU2206353 were 98.82% and 99.04%, respectively. Conclusions:Through morphological observation, biochemical identification, mass spectrometry identification, 16S rRNA and whole-genome sequencing, this pathogenic strain is identified as Yokenella regensburgei. This rare bacterium is sensitive to most detected antibiotics. This study provides diagnostic and treatment experience for Yokenella regensburgei-related infections.

Objective To explore the effect of food improvement on the retention time of nasogastric tube in stroke patients with dysphagia. Methods Sixty cases were assigned to the control group(30 cases) and the experimental group(30 cases) by random digits table method, the control group received routine nasogastric feeding, and the experimental group were given texture modified foods and thickened liquid to try to help them eating through the mouth. The feeding tube was pull out when the person in experimental group was capable of taking texture modified foods and thickened liquid without difficulty,while the tube was pull out when the person in control group was able to eat regular food and drink regular fluids. The retention time of nasogastric tube of two groups was compared. Results The retention time of nasogastric tube was(6.13±2.96)d in the experimental group and(18.93±7.58)d in the control group, there was significant difference (t =-8.162, P<0.01). Conclusions Food improvement can effectively shortenthe retention time of nasogastric tube in stroke patients with dysphagia.

Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.

Systemic lupus erythematosus(SLE)is a heterogeneous autoimmune disease that affects multiple organs.Extracel-lular vesicles(EVs),including exosomes,microparticles and apoptotic bodies,are released by most types of cells and carry nucleic acids,proteins and lipids,which play a crucial role in communication among cells.In SLE,extracellular vesicles can act as autoadju-vants to enhance the formation of immune complexes and maintain inflammatory states.In this review,the biological origin and mes-senger role of EVs in cell communication are reviewed,and the research progress of EVs in immune regulation and pathogenesis in SLE is highlighted.

Objective:The drug-resistant genes carried by carbapenem-resistant Klebsiella pneumoniae(CRKP)limit clinical treatment options,and its virulence genes severely affect patient prognosis.This study aims to investigate the distribution of virulence genes,capsular serotypes,and molecular epidemiological characteristics of CRKP in ICU,to understand the characteristics of CRKP infections in ICU,and to provide a scientific basis for effective monitoring and control of CRKP infections in ICU. Methods:A total of 40 non-duplicate strains of CRKP isolated from the ICU of Guangdong Provincial People's Hospital between January 2021 and December 2022 were collected and analyzed.Whole-genome sequencing was used to analyze the distribution of resistance genes,virulence genes,and capsular serotypes of the strains.The sequences of 7 housekeeping genes of CRKP genome were uploaded to the Klebsiella pneumoniae(KPN)multilocus sequence typing(MLST)database to determine the sequence types(STs)of the strains. Results:The age of the 40 ICU CRKP-infected patients was(69.03±17.82)years old,with various underlying diseases,and there were 20 patients with improved clinical outcome and 20 patients with death.The isolated strains primarily originated from mid-stream urine and bronchoalveolar lavage fluid.Whole-genome sequencing results revealed that the strains predominantly carried blaKPC-1(29 strains,72.5%)and blaNDM-1(6 strains,15.0%),with 5 strains carrying both blaKPC-1 and blaNDM-1.Various virulence genes were detected,among which the carriage rates of genes such as entA,entB,entE,entS,fepA,fepC,fepG,yag/ecp,and ompA reached 100%,while the carriage rates of genes such as entD,fimB,iroB,iroD,fes,and pla were low.The CRKP strains isolated from ICU were predominantly ST11(27 cases,67.5%),with KL64 being the main capsular serotype(29 cases,72.5%).A total of 23 ST11-KL64 CRKP strains were detected,accounting for 57.5%. Conclusion:The main type of ICU CRKP is ST11-KL64,carrying various virulence genes,primarily those related to iron absorption.Furthermore,blaKPC has shifted from blaKPC-2 to blaKPC-1.Therefore,close monitoring of the molecular epidemiological changes of CRKP is necessary,and strict control measures should be implemented to effectively curb the occurrence of CRKP infections.