Objective To explore the effect of Evodiamine (Evo) on the immune function of allergic rhinitis (AR) rats and the regulatory mechanism on C-C motif chemokine ligand 2 (CCL2)/ C-C motif chemokine receptor 2 (CCR2) pathway. Methods The related targets of Evo-AR-immune function were screened by network pharmacology, and the protein interaction network diagram of intersecting targets was constructed. The AR rat model was established by ovalbumin (OVA) combined with aluminium hydroxide, and the rats were divided into six groups: a normal control (NC) group, a model group, a Loratadine (LOR) group, an Evodiamine low dose (Evo-L) group, a Evodiamine high dose (Evo-H) groups, and an Evo-H combined with CCL2 group. After the last administration, the symptoms of rats in each group were scored; ELISA was applied to detect the levels of histamine, immunoglobulin E (IgE), interleukin 4 (IL-4), IL-13 and interferon γ (IFN-γ); Diff-Quick staining solution was applied to detecte the number of cells in the nasal lavage fluid (NALF); hematoxylin eosin (HE) staining was applied to observe the pathological changes of nasal mucosa tissue; real-time quantitative PCR was applied to detect the levels of CCL2 and CCR2 mRNA in tissue; Western blot was applied to detect the expression levels of CCL2, CCR2 and CXC motif chemokine ligand 8 (CXCL8) proteins in nasal mucosa. Results There were eight intersection targets of EVo-AR-immune function, and protein interaction network diagram showed that CXCL8 was the core target. Compared with the NC group, the score of nasal symptoms, the levels of histamine, IgE, IL-4 and IL-13, the numbers of eosinophil, macrophages, neutrophils, lymphocytes and total cells, the mRNA and protein expression levels of CCL2 and CCR2, and the expression of CXCL8 protein in the model group were increased, while the level of IFN-γ was decreased. Compared with the model group, the score of nasal symptoms, the levels of histamine, IgE, IL-4 and IL-13, the numbers of eosinophil, macrophages, neutrophils, lymphocytes and total cells, the mRNA and protein expression levels of CCL2 and CCR2, and the expression of CXCL8 protein in LOR and Evo groups were decreased, while the level of IFN-γ was increased. Further use of CCL2 recombinant protein for compensatory experiments revealed that the improvement effect of Evo on immune function in AR rats was reversed by CCL2. Conclusion Evo can improve the immune function of AR rats, and its mechanism may be related to the inhibition of the CCL2/CCR2 pathway.
Animals ; Receptors, CCR2/immunology* ; Signal Transduction/drug effects* ; Chemokine CCL2/immunology* ; Rats ; Rhinitis, Allergic/metabolism* ; Immunoglobulin E/blood* ; Quinazolines/pharmacology* ; Male ; Interferon-gamma ; Rats, Sprague-Dawley ; Interleukin-13 ; Histamine ; Interleukin-4/immunology* ; Disease Models, Animal

Objective To investigate the effects of ROCK-siRNA transfection on endothelial cell senescence and endothelial microparticles (EMPs) induced by angiotensin II (Ang II). Methods Human umbilical vein endothelial cells (HUVECs) were treated with Ang II (1.0 μmo/L) to induce cellular senescence models, followed by transfection with ROCK-siRNA. The cells were divided into four groups: control group, model group, negative transfection control group (Ang II combined with NC-siRNA), and ROCK-siRNA transfection group (Ang II combined with ROCK-siRNA). Cellular senescence was assessed by SA-β-Gal staining. EMP levels in cell supernatants and intracellular reactive oxygen species (ROS) levels were assessed using flow cytometry. The expression levels of silenced information regulator 1(SIRT1) and p53 protein in each group were analyzed by Western blotting. Results Following ROCK-siRNA transfection, the number of senescent cells induced by Ang II was significantly reduced, accompanied by decreased CD31⁺ EMP levels and suppressed intracellular ROS levels. Meanwhile, the expression levels of SIRT1 were up-regulated, while the expression levels of p53 were down-regulated. Conclusion Silencing ROCK expression suppresses EMP release, reduces ROS generation, regulates the expression of SIRT1 and p53, and ultimately attenuates Ang II-induced endothelial cell senescence.
Humans ; Angiotensin II/pharmacology* ; Cellular Senescence/genetics* ; Human Umbilical Vein Endothelial Cells/cytology* ; RNA, Small Interfering/metabolism* ; Reactive Oxygen Species/metabolism* ; Sirtuin 1/genetics* ; Transfection ; Tumor Suppressor Protein p53/genetics* ; Cell-Derived Microparticles/drug effects* ; rho-Associated Kinases/metabolism* ; Endothelial Cells/metabolism* ; Cells, Cultured

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β₂-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.
Humans ; Multiple Myeloma/drug therapy* ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Treatment Outcome ; Hematologic Diseases

OBJECTIVE: To investigate the phenotypes and gene frequencies of Kell blood group system K antigen and Rh blood group system D antigen in Xinjiang, and summarize and understand the distribution of Kell(K) blood type and Rh(D) blood type in this area. METHODS: A total of 12 840 patients who met the inclusion criteria during physical examination and treatment in our hospital and 18 medical institutions in our district from January 1, 2019 to December 31, 2019 were collected for identification of Kell blood group system K antigen and Rh blood group System D antigen, and the distribution of K and D blood groups in different regions, genders and nationalities were investigated and statistically analyzed. RESULTS: The proportion of K positive in the samples was 1.39%, the highest was 1.91% in southern Xinjiang, and the lowest was 1.03% in northern Xinjiang(P<0.01). The proportion of Rh(D) negative samples was 2.75% and the gene frequency was 16.64%. The proportion of Rh(D) negative samples was 4.03% and the gene frequency was 20.10% in southern Xinjiang, followed by eastern Xinjiang and the lowest in northern Xinjiang (P<0.01). The frequency of K antigen in Uygur nationality was the highest, reaching 2.16%, Kirgiz 1.54%, and the distribution trend of D/d antigen was similar to that of K antigen. Among women, the K positive frequency of Kazak nationality was slightly higher than that of Mongolian nationality. The highest proportion of K positive in Uygur women was 2.38%, which was higher than that in Uygur men (1.86%). The frequency of d phenotype in Kazak women was 3.15%, which was higher than that in Kirgiz （2.89%） (P<0.01). CONCLUSION The distributions of Kell(K) and Rh(D) blood groups in northern and southern Xinjiang and eastern Xinjiang had its own unique characteristics and differences. There are significant differences in blood group distribution among different ethnic groups and gender groups. In the future, k antigen detection can be included to further improve the investigation on the distribution of Kell blood group system in this region.
Female ; Humans ; Male ; Asian People ; China ; Ethnicity ; Gene Frequency ; Kell Blood-Group System/genetics* ; Rh-Hr Blood-Group System/genetics*

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

OBJECTIVE: To establish a stable mouse model of acquired aplastic anemia. METHODS: Female BALB/C mice aged 6 months were intraperitoneally injected with cyclophosphamide and cyclosporine for 14 days. The number of peripheral blood cells, the concentration of hemoglobin, the number of bone marrow nucleated cells, bone marrow smear, bone marrow pathological sections and other indexes were observed. RESULTS: In BALB/C mice injected intraperitoneally with cyclophosphamide and cyclosporine, the number of peripheral blood cells and the concentration of hemoglobin were significantly decreased, especially the white blood cells and platelets. Bone marrow smear showed a significant decrease in the number of nucleated cells and bone marrow hyperplasia. Bone marrow pathology showed decreased hematopoietic cells and increased non-hematopoietic cells such as adipocytes. CONCLUSION The mouse model with intraperitoneal injection of cyclophosphamide and cyclosporine can meet the diagnostic criteria of acquired aplastic anemia, which can be used as a mouse model for the study of the pathogenesis and treatment of acquired aplastic anemia.
Anemia, Aplastic ; Animals ; Bone Marrow ; Cyclophosphamide ; Cyclosporine ; Female ; Mice ; Mice, Inbred BALB C

OBJECTIVE: To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma. METHODS: Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified. RESULTS: 44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013). CONCLUSION CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.
Histones ; Humans ; Multiple Myeloma/genetics* ; Neoplasm Recurrence, Local ; Oligopeptides/therapeutic use* ; Prognosis ; Receptors, CXCR4

OBJECTIVE: To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation. METHODS: The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups. RESULTS: The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups. CONCLUSION Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.
Child ; Child, Preschool ; Graft vs Host Disease/complications* ; Hematopoietic Stem Cell Transplantation ; Humans ; Quality of Life ; Retrospective Studies ; Thalassemia/therapy* ; beta-Thalassemia/therapy*

OBJECTIVE: To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors. METHODS: The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients. RESULTS: Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis. CONCLUSION Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.
Aged ; Female ; Hematologic Neoplasms/complications* ; Humans ; Leukemia, Myeloid, Acute/complications* ; Male ; Myelodysplastic Syndromes/complications* ; Prognosis ; Retrospective Studies