OBJECTIVE: To investigate the correlation between the types and quantities of immune cells in the graft and early immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influence on clinical prognosis. METHODS: The clinical data of 83 patients with hematological diseases who received allo-HSCT in Shanxi Bethune Hospital from September 2020 to June 2023 were retrospectively analyzed. The number of mononuclear cells (MNC), CD34⁺ cells and lymphocyte subsets (including CD3⁺T, CD3⁺CD4⁺T(Th), CD3⁺CD8⁺T(Ts), NK cells and B cells) infused into the recipients was counted, and the peripheral blood lymphocytes were detected before conditioning and on days 14, 30, 60 and 100 post-HSCT. RESULTS: Multivariate analysis showed that the number of MNC in the graft affected the recovery of CD4⁺T lymphocytes after HSCT, and the number of CD4⁺T lymphocytes in the graft affected the recovery of NK cells and B cells after HSCT. The patient age, donor sex, stem cell source, degree of HLA matching, use of ATG before HSCT, the occurrence of acute graft-versus-host disease (aGVHD) after HSCT, and viral infection all affect the early cellular immune reconstitution post-HSCT. The number of infused cells had no significant impact on the median engraftment time for neutrophils and platelets after HSCT. Patients with lower numbers of CD3⁺T, CD4⁺T and B cells in the graft were more prone to viral infection after HSCT. However, the cells in the graft had no significant effect on disease recurrence or mortality. CONCLUSION The recovery rate of lymphocyte count after allo-HSCT varies. The numbers of MNC and CD4⁺T cells in the graft may be related to the cellular immune reconstitution after HSCT, while the numbers of CD34⁺,CD3⁺T,CD8⁺T,NK and B cells have no significant effect on the cellular immune reconstruction. The numbers of CD3⁺T,CD4⁺T and B cells in the graft were negatively correlated with viral infection after HSCT, but the cellular components of the graft have no obvious influence on hematopoietic reconstitution, disease recurrence, death, recurrence-free survival(RFS) and overall survival(OS) after HSCT.
Humans ; Hematopoietic Stem Cell Transplantation ; Immune Reconstitution ; Transplantation, Homologous ; Retrospective Studies ; Graft vs Host Disease/immunology* ; Male ; Female ; Killer Cells, Natural/immunology* ; Adult ; Middle Aged ; B-Lymphocytes/immunology* ; Prognosis ; Lymphocyte Subsets/immunology* ; Adolescent

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

ObjectiveTo explore the effect of Baitouweng Tang （BTWT） on the apoptosis of human colorectal cancer HCT116 cells and decipher the underlying mechanism based on the Hedgehog （Hh） signaling pathway. MethodHCT116 cells were treated with BTWT （25， 50， 100， 200， 500， 750， and 1 000 mg·L^-1） for 24 h， and then the cell proliferation was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. Five groups were designed for the treatment of HCT116 cells， including a blank control group， BTWT groups （125， 250， and 500 mg·L^-1）， and a positive control （5-fluorouracil， 5-FU， 40 mmol·L^-1） group. The cell morphology was observed under an inverted microscope. The migration of the cells was detected by scratch test， and the apoptosis by Hoechest 33324/propidium iodide （PI） staining and flow cytometry. Western blot was employed to determine the protein levels of sonic hedgehog （SHh）， GLI family zinc finger protein 1 （Gli1）， smoothened （Smo）， suppressor of fused （SuFu）， cellular-myelocytomatosis viral oncogene （c-Myc）， and the apoptosis-related proteins B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）. The quantitative real-time reverse transcription PCR （Real-time PCR） was employed to determine the mRNA levels of Bax， Bcl-2， SHh， Gli1， Smo， SuFu， and c-Myc. ResultCompared with the blank control group， BTWT changed the cell morphology （making the cell become round with dense nucleus）， inhibited the proliferation of HCT116 cells in a dose-dependent manner， decreased the ability of migration （P<0.05， P<0.01）， and increased apoptotic cells. Compared with the blank control group， BTWT （500 mg·L^-1） treatment for 24 h up-regulated the protein and mRNA levels of Bax （P<0.05， P<0.01） and down-regulated the protein and mRNA levels of Bcl-2 in HCT116 cells （P<0.05， P<0.01）. Moreover， the treatment down-regulated the mRNA and protein levels of SHh， Gli1， Smo， and c-Myc （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of SuFu （P<0.05， P<0.01）. ConclusionBTWT inhibited the proliferation and migration and induced the apoptosis of colorectal cancer HCT116 cells by down-regulating the Hh signaling pathway.

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism. METHODS: A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected. RESULTS: After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment ( CONCLUSION Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.
Acupuncture Points ; Aged ; Dopamine ; Electroacupuncture ; Humans ; Melatonin ; Sleep Initiation and Maintenance Disorders/therapy*

OBJECTIVE To investigate the pharmacological effect of ursolic acid (UA) on colitis-associated colorec?tal cancer (CAC) and its underlying mechanism based on the Wnt signaling pathway. METHODS The CAC model in mice was established by azoxymethane (AOM) combined and dextran sulfate sodium salt (DSS), accompanied by treat?ment with various dosages of UA and concomitant appraisal of body weight, stool and physical state of the mice. After the sacrifice of the mice, the tumor and length of the colorectum were measured, followed by retrieval of the liver, spleen, thymus and tumor tissue for downstream assays. The levels of inflammatory factors interleukin-6 (IL-6), IL-1βand C-reactive protein (CRP) in the tumor and serum were examined by enzyme-linked immunosorbent assay (ELISA). The pathological changes of colorectal tissues were observed by HE staining. The levels in tumors of Wnt/β-catenin sig?naling pathway-related proteins Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry (IHC). The mRNA expressions of Wnt4, GSK-3β,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, Bax, caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR (RT-qPCR). The protein levels of Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, phospho-β-catenin, phospho-GSK-3β, Bcl-2 and Bax in tumors were probed by analyzed by Western blotting (WB). Also, RNA-seq was employed to assess the gut microbiota in the mice. RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC, evidenced by improved physical state, body weight, survival rate, colorectal length, the mass of liver, thy?mus, spleen, and decreased CAC load and colorectal mass. UA attenuated the levels of IL-6, IL-1β and CRP in the mouse serum and colorectal tumor in a dose-dependent manner. HE staining showed that UA lessened carcinogenesis in the colorectum, with lower infiltration of lymphocytes, versus the control. IHC indicated that UA mitigated the expres?sion of Wnt4,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and promoted the GSK-3βexpression, compared with the control. Furthermore, UA diminished the mRNA expressions of Wnt4, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and heightened the mRNA levels of GSK-3β, caspase-3, capase-9 and Bax in CAC. The results of mRNA expressions were verified by WB analysis, which revealed that UA impeded the protein expression of Wnt4,β-catenin, c-Myc, cyclin D1, Bcl-2, TCF4, LEF1, and elevated the protein levels of GSK-3βand Bax, phospho-β-catenin in mouse CAC. In addi?tion, UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC. CONCLU?SION Ursolic acid may protect against CAC, potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

Abstract　　Spleen tyrosine kinase (SYK) is not only a key kinase in the B-cell receptor (BCR) signaling pathway, but also a critical component of other signal transduction pathways such as Fc receptor, complement receptor and integrin. Abnormal activation of SYK closely related to the occurrence and development of hematological malignancies, thus targeting SYK has become a research hotspot. Several SYK inhibitors including Fostamatinib, Entospletinib and Cerdulatinib were being evaluated in clincal trials. As a second generation SYK inhibitor, Entospletinib has achieved good efficacy in lymphoid and myeloid hematologic tumors. Furthermore, Entospletinib can significantly relieve hematopoietic stem cell transplantation(HCT) related graft versus host disease (GVHD). In this review the role of SYK inhibitors in treatment of hematological malignancies is summarized brifely.
Graft vs Host Disease ; Hematologic Neoplasms ; Humans ; Protein Kinase Inhibitors ; Spleen ; Syk Kinase

Abstract　　In recent years, development of the targeted drugs according to the biological characteristics of tumors have provided more treatment options for tumor patients. It was found that the overactivation or abnormality of B cell receptor (BCR) signal pathway closely related to the occurrence and development of various B cell tumors, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a key kinase in the BCR pathway, BTK inhibitors have obvious anti-tumor effect when its activity is being inhibitered. Currently, BTK inhibitors developed include the first-generation Ibrutinib and the second-generation Acalabrutinib, which can be targeted at the inhibition of BTK and its downstream signaling pathway, and have important therapeutic value for a variety of B-cell tumors, such as CLL and partial non-Hodgkin's lymphoma (NHL). However, its side effects and drug-resistance also gradually emerged, effective drug combination therapy has shown a certain clinical activity. This reviews summarizes briefly the mechanism and status of BTK inhibitors in the treatment of various B-cell tumors.

Objective: Recent studies have shown the important influence of various micro factors on the general biological activity and function of endothelial cells (ECs). Vascular endothelial growth factor (VEGF) and angiogenin (ANG) are classic micro factors that promote proliferation, differentiation, and migration of ECs. The underlying pathophysiological mechanisms and related pathways of these micro factors remain the focus of current research. Data sources: An extensive search was undertaken in the PubMed database by using keywords including "micro factors" and "endothelial cell." This search covered relevant research articles published between January 1, 2007 and December 31, 2018. Study selection: Original articles, reviews, and other articles were searched and reviewed for content on micro factors of ECs. Results: VEGF and ANG have critical functions in the occurrence, development, and status of the physiological pathology of ECs. Other EC-associated micro factors include interleukin 10, tumor protein P53, nuclear factor kappa B subunit, interleukin 6, and tumor necrosis factor. The results of Gene Ontology analysis revealed that variations were mainly enriched in positive regulation of transcription by the RNA polymerase II promoter, cellular response to lipopolysaccharides, negative regulation of apoptotic processes, external side of the plasma membrane, cytoplasm, extracellular regions, cytokine activity, growth factor activity, and identical protein binding. The results of the Kyoto Encyclopedia of Genes and Genomes analysis revealed that micro factors were predominantly enriched in inflammatory diseases. Conclusions In summary, the main mediators, factors, or genes associated with ECs include VEGF and ANG. The effect of micro factors on ECs is complex and multifaceted. This review summarizes the correlation between ECs and several micro factors.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

AIM:To investigate the ameliorative effect of salvianolic acid B on vasodilatory function in diabetic rats and the possible mechanisms.METHODS:SD rats(n=40)were fed on high-sugar and high-fat diet for 4 weeks, followed by a single intraperitoneal injection of streptozotocin(40 mg/kg).The rats with random blood glucose level over 16.7 mmol/L were considered diabetic and randomly allocated to 3 groups, namely model group, low dose(80 mg· kg-1· d-1)of salvianolic acid B group and high dose(160 mg· kg-1· d-1)of salvianolic acid B group.The rats in salvianolic acid B groups were intragastrically administered with corresponding doses of salvianolic acid B for 6 weeks. Vasodilatory function was measured as endothelium-dependent and-independent vasodilation of the aortic rings.The primary histopathological changes of aorta were observed by HE staining.Serum levels of interleukin-6(IL-6),tumor necrosis fac-tor-α(TNF-α)and C-reactive protein(CRP)were measured by ELISA.The levels of total antioxidant capacity,malondi-aldehyde(MDA)and nitric oxide(NO)in aortic tissues were evaluated by colorimetric assays.The protein levels of inter-cellular adhesion molecule-1(ICAM-1)and monocyte chemotactic protein-1(MCP-1), and the activation of nuclear fac-tor-κB(NF-κB)were determined by Western blot.RESULTS: Treatment with salvianolic acid B evidently ameliorated endothelium-dependent diastolic function and pathological changes of aorta in diabetic rats(P<0.05 or P<0.01).Sup-plementation with salvianolic acid B resulted in significant increases in NO content and total antioxidant capacity in aortic tissues,accompanied by marked decreases in the level of MDA in aorta tissues and the serum levels of IL -6, TNF-αand CRP(P<0.05 or P<0.01).Salvianolic acid B markedly down-regulated NF-κB p65 nuclear translocation and protein expression of ICAM-1 and MCP-1 in aorta tissues(P<0.05 or P<0.01).CONCLUSION:Salvianolic acid B effectively ameliorates endothelium-dependent diastolic function of aorta in diabetic rats, which might be attributed to suppression of NF-κB activation and subsequent expression of inflammatory cytokines.The beneficial effect of salvianolic acid B on vascu-lar endothelium might be derived from its antioxidant capacity.