Objective:To investigate the effect of single nucleotide polymorphism (SNP) of FCN gene on the susceptibility of pre-eclampsia (PE) in Han nationality pregnant women.Methods:A total of 274 PE pregnant women (PE group) and 154 healthy pregnant women (control group) admitted to Boai Hospital of Zhongshan, Affiliated Hospital to Southern Medical University from October 2020 to October 2022 were collected. The general information, medical history, reproductive history, blood pressure, body mass index and blood biochemical indicators before delivery were compared between the two groups. Twenty-three SNP loci of FCN gene family were genotyped by time-of-flight mass spectrometry, and the serum levels of ficolins (ficolin-1, -2 and -3) were detected by enzyme-linked immunosorbent assay.Results:(1) Compared with the control group, the body mass index, mean arterial pressure, gestational age at delivery, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, direct bilirubin, albumin, and C-reactive protein in the PE group were significantly higher than those in the control group (all P<0.05). The levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), placental growth factor (PlGF) and human soluble vascular endothelial growth factor receptor-1 (sFlt-1) were significantly different between the two groups (all P<0.05). (2) Among the 23 SNP loci in FCN gene family, 18 loci were in Hardy-Weinberg genetic equilibrium, including 5 loci in FCN1 gene, 10 loci in FCN2 gene, and 3 loci in FCN3 gene. Five loci that did not conform to Hardy-Weinberg genetic equilibrium were not included in the subsequent analysis. Compared with the control group, the genotype distribution of 3 loci of FCN2 gene (rs7872508, rs11103563, rs73664188) and 1 locus of FCN3 gene (rs3813800) in the PE group were significantly different (all P<0.05). After Bonferroni correction, only the genotype distribution of rs7872508 and rs73664188 in FCN2 gene were statistically different between the PE group and the control group (all P<0.05). Further analysis showed that for the rs7872508 locus of FCN2 gene, compared with GG genotype, genotype GT ( OR=3.025, 95% CI: 1.080-8.471) and TT ( OR=4.777, 95% CI: 1.758-12.979) both significantly increased the risk of PE (both P<0.05). For rs73664188 locus of FCN2 gene, compared with TT genotype, genotype TC ( OR=0.510, 95% CI: 0.334-0.778) significantly reduced the risk of PE ( P<0.05). (3) Compared with the control group, the serum levels of ficolin-1 and ficolin-2 in pregnant women in the PE group were significantly reduced (both P<0.05), while the level of ficolin-3 showed no significant change ( P=0.271). Correlation analysis showed that the serum levels of ficolin-2 in pregnant women in the PE group were significantly positively correlated with PlGF level ( r=0.321, P<0.001), and significantly negatively correlated with sFlt-1 level ( r=-0.187, P=0.002) and NT-proBNP level ( r=-0.392, P<0.001). Further analysis revealed that the serum levels of ficolin-2 in pregnant women of the PE group with GT and TT genotypes at rs7872508 locus of FCN2 gene were significantly reduced (both P<0.05), while the serum level of ficolin-2 in pregnant women of the PE group with TC genotype at the rs73664188 locus were significantly increased ( P<0.05). Conclusion:The SNP of FCN2 gene in FCN gene family might be related to the susceptibility to PE and have an effect on serum ficolin-2 level in PE pregnant women.

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.

Humans ; Non-alcoholic Fatty Liver Disease ; Prospective Studies ; Risk Factors ; Exercise ; Liver

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 μmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; bcl-2-Associated X Protein ; Vimentin/metabolism* ; Cell Proliferation ; Signal Transduction ; Apoptosis ; Cell Line, Tumor ; Colorectal Neoplasms/genetics* ; Cadherins/genetics* ; Cell Movement

OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.
Humans ; Adolescent ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Acute Disease ; Prognosis ; Leukemia-Lymphoma, Adult T-Cell/therapy* ; Nuclear Pore Complex Proteins

OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed. RESULTS: Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m² d1 + oxaliplatin 100 mg/m² d 1 + etoposide 60 mg/m² d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later. CONCLUSION PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.
Humans ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies ; Etoposide ; Neoplasm Recurrence, Local/drug therapy* ; Asparaginase ; Deoxycytidine ; Lymphoma, T-Cell, Peripheral/drug therapy* ; Lymphoma, Extranodal NK-T-Cell/therapy* ; Oxaliplatin/therapeutic use*

OBJECTIVE: To screen better promoters and provide more powerful tools for basic research and gene therapy of hemophilia. METHODS: Bioinformatics methods were used to analyze the promoters expressing housekeeping genes with high abundance, so as to select potential candidate promoters. The GFP reporter gene vector was constructed, and the packaging efficiency of the novel promoter was investigated with EF1 α promoter as control, and the transcription and activities of the reporter gene were investigated too. The activity of the candidate promoter was investigated by loading F9 gene. RESULTS: The most potential RPS6 promoter was obtained by screening. There was no difference in lentiviral packaging between EF1 α-LV and RPS6-LV, and their virus titer were consistent. In 293T cells, the transduction efficiency and mean fluorescence intensity of RPS6pro-LV and EF1 αpro-LV were proportional to the lentiviral dose. The transfection efficiency of both promoters in different types of cells was in the following order: 293T>HEL>MSC; Compared with EF1 αpro-LV, RPS6pro-LV could obtain a higher fluorescence intensity in MSC cells, and RPS6pro-LV was more stable in long-term cultured HEL cells infected with two lentiviruses respectively. The results of RT-qPCR, Western blot and FIX activity (FIX∶C) detection of K562 cell culture supernatant showed that FIX expression in the EF1 α-F9 and RPS6-F9 groups was higher than that in the unloaded control group, and there was no significant difference in FIX expression between the EF1 α-F9 and RPS6-F9 groups. CONCLUSION After screening and optimization, a promoter was obtained, which can be widely used for exogenous gene expression. The high stability and viability of the promoter were confirmed by long-term culture and active gene expression, which providing a powerful tool for basic research and clinical gene therapy of hemophilia.
Humans ; Transduction, Genetic ; Genetic Vectors ; Hemophilia A/genetics* ; Transfection ; Blood Coagulation Factors/genetics* ; Lentivirus/genetics*

Bone marrow microenvironment is a highly complex environment surrounding tumor, which plays an important role in the survival, proliferation, drug resistance and migration of multiple myeloma (MM) cells. As an important cellular component in tumor microenvironment, tumor-associated macrophages(TAM) has attracted attention due to its key role in tumor progression and drug resistance. Targeting TAM has shown potential therapeutic value in cancer treatment. In order to clarify the role of macrophages in MM progression, it is necessary to understand the differentiation of TAM and its characteristics of promoting MM. This paper reviews the research progress on how TAM is programmed in MM and the mechanism of TAM promoting tumor development and drug resistance.
Humans ; Multiple Myeloma/pathology* ; Tumor-Associated Macrophages ; Macrophages/pathology* ; Cell Differentiation ; Tumor Microenvironment

OBJECTIVE: To investigate the risk factors and prognosis of cardiovascular damage in hypereosinophilia (HE). METHODS: The clinical data of 62 patients with HE in Gansu Provincial Hospital from January 2015 to December 2020 were retrospectively analyzed, including clinical characteristics and laboratory indicators, and the influencing factors of survival and prognosis were also analyzed. RESULTS: In this study, there were 34 males and 28 females, with a median age of 53.5 (20-79) years, 35 patients without cardiovascular damage, 27 patients with cardiovascular damage, including 22 patients with abnormal electrocardiogram (ECG) (81.5%), 18 patients with abnormal echocardiography (ECHO) (66.7%), 9 patients with single ECG abnormality, 5 patients with single ECHO abnormality, and other 13 patients with multiple abnormalities. In cardiovascular damage group, peripheral white blood cell count, absolute value of eosinophils, troponin T (TNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-4 and IL-5 levels at initial diagnosis were significantly higher than those in the non-cardiovascular damage group (P <0.01), while hemoglobin, IL-2 and interferon-γ levels were significantly lower (P <0.01). There were no significant differences in age, sex, course of disease, etiological classification, platelet count, serum creatine kinase, serum creatine kinase isoenzyme and lactate dehydrogenase between the two groups (P >0.05). The 5-year overal survival rate of patients with cardiovascular damage was 88.9%, and that of patients without cardiovascular damage was 100%, the difference was statistically significant (P =0.012). The 5-year event-free survival (EFS) rate of patients with cardiovascular damage was 59.3%, and the median time was 37 (21-52) months, while that of patients without cardiovascular damage was 80%, and the median time was 63 (51-74) months (P =0.002). Age (>60 years old), course of disease (>24 months), NT-proBNP (>3 000 pg/ml), TNT (>100 ng/L), elevated IL-4 and IL-5 were associated with EFS shortening in patients with cardiovascular damage, which were independent risk factors for EFS. CONCLUSION The EFS rate in HE patients without cardiovascular damage is significantly higher than patients with cardiovascular damage. Age, course of disease, NT-proBNP, TNT, IL-4 and IL-5 are independent risk factors affecting EFS of patients with cardiovascular damage.
Male ; Female ; Humans ; Middle Aged ; Aged ; Interleukin-4 ; Biomarkers ; Retrospective Studies ; Interleukin-5 ; Prognosis ; Risk Factors ; Eosinophilia ; Peptide Fragments ; Natriuretic Peptide, Brain

OBJECTIVE: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI). METHODS: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed. RESULTS: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M₂). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. CONCLUSION Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Dexamethasone/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Bortezomib/therapeutic use* ; Renal Insufficiency/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*