Objective:To explore the difference of type 2 innate lymphoid cell(ILC2),IL-9 and related cytokines between chronic lymphocytic leukemia(CLL)patients and normal individuals,as well as the correlation between ILC2 and IL-9 and other cytokines in CLL patients.Methods:Flow cytometry was used to detect the expression of ILC2 and regulatory T cells(Tregs)in peripheral blood of 26 CLL patients at initial diagnosis and 10 healthy controls.RT-qPCR was used to detected IFN-γ,TGF-β,IL-9 and IL-10 mRNA in peripheral blood mononuclear cell(PBMC).ELISA was used to detect serum IFN-γ,TNF-α,TGF-β,IL-9,IL-10 and IL-21.ILC2 and IL-9 were observed in the cervical lymph node of 12 CLL patients at initial diagnosis and 12 patients with reactive lymphoid hyperplasias by multiplex indirect immunofluorescence staining.Spearman test was used to analyze the correlation between peripheral blood ILC2 and IL-9,IL-9 and IL-21,IFN-γ mRNA and IL-10 mRNA in CLL patients.Pearson test was used to analyze the correlation between TNF-α and TGF-β in CLL patients.Results:Compared with control group,the proportions of ILC2 and Tregs were significantly increased in CLL group(both P＜0.05).The mRNA expressions of IFN-γ,IL-9,IL-10 and TGF-β in PBMCs of CLL patients were significantly increased(all P＜0.05).In CLL patients,the expressions of IFN-γ,TNF-α,TGF-β,IL-9 and IL-10 in serum were significantly increased(all P＜0.01),while IL-21 slightly increased without statistical difference(P＞0.05).In CLL patients,the peripheral blood ILC2 was positively related to IL-9(r=0.56),IL-9 was positively related to IL-21(r=0.397),IFN-γ mRNA was positively related to IL-10 mRNA(r=0.623),and TNF-α was positively related to TGF-β(r=0.577).Compared with reactive lymphoid hyperplasias patients,the mean fluorescence intensities of GAT A3 and CRTH2 representing ILC2 and IL-9 in cervical lymph nodes were significantly increased in the CLL group(all P＜0.001),and showed colocalization.Conclusion:In CLL patients,the proportions of ILC2 and IL-9 in peripheral blood and lymph nodes increase,and ILC2 and IL-9 show colocalization in lymph nodes.There is a positive correlation between ILC2 and IL-9 in the peripheral blood of CLL patients,the ability of ILC2 to secrete IL-9 is increased,and ILC2 may affect the occurrence and development of CLL through IL-9.

Aim To explore the effect of neurite out-growth inhibitor A/neurite outgrowth inhibitor receptor(Nogo-A/NgR)pathway on psychedelic-reduced pre-pulse inhibition in mice.Methods Mice were injec-ted intraperitoneally with psilocybin,DOI to establish an animal model of prepulse inhibition(PPI)reduc-tion.The effects of psilocybin and DOI on PPI in mice after lateral ventricular injection of Nogo-A inhibitor NEP1-40 30 min in advance were evaluated.Finally,Rtn4r knockout mice were constructed to further verify the conclusion.Results The injection of NEP1-40(1 g·L-1,5 μL/mice,i.c.v)30 min in advance had no effect on PPI of mice.Under the conditions of 70 dB and 75 dB prepulse stimulation,NEP1-40 significantly up-regulated the PPI reduction induced by psilocybin.At the same time,NEP1-40 significantly up-regulated the DOI induced PPI reduction in mice at 70 dB and 80 dB prepulse stimulation.Compared with the two solvent groups,the PPI of Rtn4r-/-mice was not differ-ent from that of wild-type mice.Compared with the mice in Rtn4r-/-solvent group,the PPI of mice in Rtn4r-/-administration group showed a decreasing trend,but had no significant difference.Under the con-dition of 70 dB prepulse stimulation,there was a signif-icant difference between the Rtn4r-/-administration group and wild-type mice.Conclusion Nogo-A/NgR pathway is involved in the destruction of sensorimotor gating in mice by the psychedelic psilocybin or DOI.

Aim To explore the effect of neurite out-growth inhibitor A/neurite outgrowth inhibitor receptor(Nogo-A/NgR)pathway on psychedelic-reduced pre-pulse inhibition in mice.Methods Mice were injec-ted intraperitoneally with psilocybin,DOI to establish an animal model of prepulse inhibition(PPI)reduc-tion.The effects of psilocybin and DOI on PPI in mice after lateral ventricular injection of Nogo-A inhibitor NEP1-40 30 min in advance were evaluated.Finally,Rtn4r knockout mice were constructed to further verify the conclusion.Results The injection of NEP1-40(1 g·L-1,5 μL/mice,i.c.v)30 min in advance had no effect on PPI of mice.Under the conditions of 70 dB and 75 dB prepulse stimulation,NEP1-40 significantly up-regulated the PPI reduction induced by psilocybin.At the same time,NEP1-40 significantly up-regulated the DOI induced PPI reduction in mice at 70 dB and 80 dB prepulse stimulation.Compared with the two solvent groups,the PPI of Rtn4r-/-mice was not differ-ent from that of wild-type mice.Compared with the mice in Rtn4r-/-solvent group,the PPI of mice in Rtn4r-/-administration group showed a decreasing trend,but had no significant difference.Under the con-dition of 70 dB prepulse stimulation,there was a signif-icant difference between the Rtn4r-/-administration group and wild-type mice.Conclusion Nogo-A/NgR pathway is involved in the destruction of sensorimotor gating in mice by the psychedelic psilocybin or DOI.

Objective:To investigate effect of rapamycin on proliferation of human chronic lymphoblastic leukemia tumor cell MEC-1 in vitro.Methods:Human γδT cells were cultured and expanded in vitro.Human γδT cells percentage was detected by flow cytometry on the 10th day.γδT cells were treated with different concentrations of rapamycin(0,50,100 and 200 nmol/L).After 48 h of intervention,IL-17,IL-12,IFN-γ and TNF-α contents secreted by γδT cells were determined by ELISA,and AKT/mTOR protein expression was detected by Western blot.Supernatant of γδT was collected and co-cultured with MEC-1 indirectly.Co-cultured experi-mental was divided into DMSO group,rapamycin group,γδT group,rapamycin treated γδT group and control group.Survival rate of MEC-1 cells in each group was determined by CCK-8 after 48 h of culture.Results:IL-12,IFN-γ and TNF-α levels secreted by γδT cells were the highest when rapamycin was 100 nmol/L,which was significantly higher than other groups(P<0.05).When rapamycin was 50 nmol/L,IL-17 secretion level of γδT cells was the highest,and IL-17 level secreted by γδT cells gradually decreased with increase of rapamycin concentration.Survival rates of MEC-1 cells in supernatant of DMSO group,rapamycin group,rapamycin treated γδT cell group and γδT cell group were(93.48±2.52)%,(71.44±4.31)%,(83.93±1.54)%and(57.97±2.47)%,whose differences were statistically significant compared with control group(P<0.05).Compared with control group,mTOR protein level of γδT cells was decreased in all rapamycin treated groups.Protein expressions of upstream AKT,pAKT and downstream specific transcription factor 4EBP-1 were decreased with increase of rapamycin concentration(P<0.05).Conclusion:There is a dose-effect relationship between rapamycin concentration and IL-17,IL-12,IFN-γ,TNF-α secretions by γδT cells.Rapamycin and γδT cells can inhibit pro-liferation of MEC-1 cells,and 100 nmol/L rapamycin can enhance inhibitory effect of γδT cells on proliferation of MEC-1 cells.Rapa-mycin can weaken AKT pathway on γδT cells,and rapamycin combined with γδT cells plays a positive role in anti-tumor application of leukemia.

Objective:To explore the difference of type 2 innate lymphoid cell(ILC2),IL-9 and related cytokines between chronic lymphocytic leukemia(CLL)patients and normal individuals,as well as the correlation between ILC2 and IL-9 and other cytokines in CLL patients.Methods:Flow cytometry was used to detect the expression of ILC2 and regulatory T cells(Tregs)in peripheral blood of 26 CLL patients at initial diagnosis and 10 healthy controls.RT-qPCR was used to detected IFN-γ,TGF-β,IL-9 and IL-10 mRNA in peripheral blood mononuclear cell(PBMC).ELISA was used to detect serum IFN-γ,TNF-α,TGF-β,IL-9,IL-10 and IL-21.ILC2 and IL-9 were observed in the cervical lymph node of 12 CLL patients at initial diagnosis and 12 patients with reactive lymphoid hyperplasias by multiplex indirect immunofluorescence staining.Spearman test was used to analyze the correlation between peripheral blood ILC2 and IL-9,IL-9 and IL-21,IFN-γ mRNA and IL-10 mRNA in CLL patients.Pearson test was used to analyze the correlation between TNF-α and TGF-β in CLL patients.Results:Compared with control group,the proportions of ILC2 and Tregs were significantly increased in CLL group(both P＜0.05).The mRNA expressions of IFN-γ,IL-9,IL-10 and TGF-β in PBMCs of CLL patients were significantly increased(all P＜0.05).In CLL patients,the expressions of IFN-γ,TNF-α,TGF-β,IL-9 and IL-10 in serum were significantly increased(all P＜0.01),while IL-21 slightly increased without statistical difference(P＞0.05).In CLL patients,the peripheral blood ILC2 was positively related to IL-9(r=0.56),IL-9 was positively related to IL-21(r=0.397),IFN-γ mRNA was positively related to IL-10 mRNA(r=0.623),and TNF-α was positively related to TGF-β(r=0.577).Compared with reactive lymphoid hyperplasias patients,the mean fluorescence intensities of GAT A3 and CRTH2 representing ILC2 and IL-9 in cervical lymph nodes were significantly increased in the CLL group(all P＜0.001),and showed colocalization.Conclusion:In CLL patients,the proportions of ILC2 and IL-9 in peripheral blood and lymph nodes increase,and ILC2 and IL-9 show colocalization in lymph nodes.There is a positive correlation between ILC2 and IL-9 in the peripheral blood of CLL patients,the ability of ILC2 to secrete IL-9 is increased,and ILC2 may affect the occurrence and development of CLL through IL-9.

Objective To investigate the effects of strength training and flexibility training on the strategy of crossing obstacles for the elderly women and the risk of tripping over obstacles.Methods Twenty five elderly women were randomly divided into strength training group(n=13)and flexibility training group(n=12),and received corresponding intervention training for 12 weeks.The kinematics data of obstacle crossing were collected using an infrared three-dimensional(3D)motion capture system before and after training.Results Both strength training and flexibility training could significantly improve the gait speed(P=0.033),stride length(P=0.020)and toe distance(P=0.014)during 25 cm obstacle crossing.The interactive effect of training and time was significant for the crossing height(15 cm:P=0.025;25 cm:P=0.019).The interactive effect of training and time was significant for the margin of stability(MOS)in the internal-external direction during 25 cm obstacle crossing(P<0.05).The minimum MOS in the first single support period(P=0.046)and the MOS at the time when the toe crossed directly above the obstacle(P=0.043)in strength training group were significantly increased.Conclusions Both strength training and flexibility training can improve the spatiotemporal characteristics of the elderly women during obstacle crossing.Compared with flexibility,muscle strength is the most important reason that restricts the crossing height of the elderly women.Strength training can effectively reduce the risk of tripping over obstacles by improving the crossing height and dynamic stability of elderly women.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.

Objective To investigate the effects of strength training and flexibility training on the strategy of crossing obstacles for the elderly women and the risk of tripping over obstacles.Methods Twenty five elderly women were randomly divided into strength training group(n=13)and flexibility training group(n=12),and received corresponding intervention training for 12 weeks.The kinematics data of obstacle crossing were collected using an infrared three-dimensional(3D)motion capture system before and after training.Results Both strength training and flexibility training could significantly improve the gait speed(P=0.033),stride length(P=0.020)and toe distance(P=0.014)during 25 cm obstacle crossing.The interactive effect of training and time was significant for the crossing height(15 cm:P=0.025;25 cm:P=0.019).The interactive effect of training and time was significant for the margin of stability(MOS)in the internal-external direction during 25 cm obstacle crossing(P<0.05).The minimum MOS in the first single support period(P=0.046)and the MOS at the time when the toe crossed directly above the obstacle(P=0.043)in strength training group were significantly increased.Conclusions Both strength training and flexibility training can improve the spatiotemporal characteristics of the elderly women during obstacle crossing.Compared with flexibility,muscle strength is the most important reason that restricts the crossing height of the elderly women.Strength training can effectively reduce the risk of tripping over obstacles by improving the crossing height and dynamic stability of elderly women.

Beta-amylases (BAMs), key enzymes in starch hydrolysis, play an important role in plant growth, development, and resistance to abiotic stress. To mine the saline-alkali tolerance-related BAM genes in alfalfa (Medicago sativa L.), we identified MsBAM genes in the whole genome. The physicochemical properties, phylogeny, gene structures, conserved motifs, secondary structures, promoter cis-acting elements, chromosome localization, and gene replication relationships of BAM gene family members were analyzed. RNA-seq and quantitative real-time PCR (qRT-PCR) were employed to analyze the expression patterns of BAM family members under saline-alkali stress. The results showed that 54 BAM genes were identified in the genome, which were classified into 8 subgroups according to the phylogenetic tree. The members of the same subgroup had similar gene structures except that those of subgroups 1 and 7 had large differences. Conserved motif analysis showed that all MsBAM proteins had a typical glycohydrolysis domain. The chromosome localization analysis showed that MsBAM gene family members were unevenly distributed on 27 chromosomes. The duplication of gene segments led to the increase in BAM gene number in alfalfa. The promoters of BAM genes contained a large number of elements in response to plant hormones and stress. Transcriptome data and qRT-PCR results showed that the expression levels of most MsBAM genes were up-regulated in response to saline-alkali stress. Under the saline-alkali stress, the expression levels of 28 genes, including MsBAM6, were up-regulated on days 1 and 7, and those of 5 genes, including MsBAM9, were up-regulated by over 2 folds. In addition, under salt-alkali stress, BAM activity and soluble sugar content were significantly increased. These results indicate that BAM genes play a key role in alfalfa in response to saline-alkali stress, laying a foundation for further research in this field.
Medicago sativa/physiology* ; beta-Amylase/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Stress, Physiological/genetics* ; Multigene Family ; Alkalies ; Plant Proteins/genetics*

With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*