OBJECTIVE: To analyze the significance of total vitamin D (tVD), total procollagen type I amino-terminal propeptide (tPINP) and β-CrossLaps (β-CTx) in the staging and prognosis of patients with multiple myeloma (MM). METHODS: A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group (MM group), and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group. The expression levels of tVD, tPINP and β-CTx in the two groups were detected by chemiluminescence method. The differences in the expression levels of tVD, tPINP and β-CTx among MM patients at different ISS stages were analyzed. The expression levels of tVD, tPINP and β-CTx in MM patients with different levels of hemoglobin (Hb), serum calcium (Ca), creatinine (Crea), albumin (ALB), β₂-microglobulin (β₂-MG) and lactate dehydrogenase (LDH) were compared. The correlations between the expression levels of tVD, tPINP, β-CTx and the aforementioned clinical parameters were analyzed, respectively. The relationship between the expression levels of tVD, tPINP, β-CTx and the progression-free survival (PFS) of MM patients was analyzed. RESULTS: The expression level of tVD in the MM group was significantly lower than that in the control group (21.73±14.45 ng/ml vs 30.78±9.94 ng/ml, P =0.022). The expression level of β-CTx in the MM group was significantly higher than that in the control group (1.43±0.99 ng/ml vs 0.53±0.29 ng/ml, P =0.013). The tVD level in MM patients with ISS stage I-II was significantly higher than that of MM patients with ISS stage III (29.50±14.59 ng/ml vs 12.62±7.73 ng/ml, P =0.028), indicating that the higher the ISS stage, the lower the tVD level. The tPINP and β-CTx levels in MM patients with high Ca levels (>2.65 mmol/L) were significantly higher than those in patients with low Ca levels (≤2.65 mmol/L) (P =0.016, P =0.021). The tVD level of MM patients was positively correlated with the ALB level (r =0.570), tPINP was positively correlated with Ca and β₂-MG levels (r =0.791,r =0.673), and β-CTx was positively correlated with tPINP level (r =0.616). The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group (P =0.041). CONCLUSION The expression level of tVD is decreased in MM patients, which can be used as an indicator to evaluate the disease stage and prognosis of the patients. The β-CTx expression level is increased in MM patients. tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.
Humans ; Multiple Myeloma/pathology* ; Procollagen/blood* ; Vitamin D/blood* ; Prognosis ; Peptide Fragments/blood* ; Collagen Type I/blood* ; Female ; Male ; Middle Aged ; Aged ; Neoplasm Staging

OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

ObjectiveThe purpose of this study was to explore the difference in expression of gene between the osteosarcoma metastasis and primary specimens through NGS detection， in order to find the molecular mechanism of inducing osteosarcoma occurrence and metastasis. MethodsNext generation sequencing （NGS） was used to detect the tumor tissue samples of paired primary and metastatic lesions in 12 patients with metastasis， including 9 pairs of Panel detection （678 genes） and 3 pairs of whole exon detection （WES）. Copy number variation was detected by Excavator. DNA mutations were detected by Lumpy fusion， and RNA mutations were detected with Defuse + Star fusion. The distribution of mutations was shown by Circos. Metascape was used to analyze the enrichment of Go and KEGG signal pathways of differential genes. Pyclone+Citup/LICHEE was used for clonal evolution analysis. ResultsThe most frequent gene mutation mode of osteosarcoma was gene amplification， high-frequency mutation genes were FLCN（37.5%），GID4（37.5%），TP53（33.3%），ATRX（25%），CALR（25%），CCND3（25%），CCNE1（25%），NOCR1（25%），TFEB（25%），VEGFA（25%）， and the mutation frequency of cell cycle pathway was the highest. KT1， PLCG2 and EGFR were closely related to the metastasis of osteosarcoma. The frequency of tumor mutation burden （TMB） in metastatic lesions was significantly higher than primary lesions （P = 0.013）. Three patients detected by WES showed linear clonal evolution， suggesting that the mutations of osteosarcoma metastasis genes may be accumulated sequentially. We identified new candidate genes that may play an important role in the progression of osteosarcoma， including PLCG2， MYO15A and PEX6. ConclusionsThe most frequent gene mutation pattern of osteosarcoma occurrence and metastasis is gene amplification， and the frequency of tumor mutation burden （TMB） in metastatic lesions is significantly higher than that in primary lesions. There is an interrelated linear gene clonal evolution in patients with metastasis. This study suggests that PLCG2， MYO15A and PEX6 may play an important role in the progression of osteosarcoma.

The minimally invasive cardiovascular surgery developed rapidly in last decades. In order to promote the development of minimally invasive cardiovascular surgery in China, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) has gradually standardized the collection and report of the data of Chinese minimally invasive cardiovascular surgery since its establishment. The total operation volume of minimally invasive cardiovascular surgery in China has achieved substantial growth with a remarkable popularization of concepts of minimally invasive medicine in 2019. The data of Chinese minimally invasive cardiovascular surgery in 2019 was reported as a paper for the first time, which may provide reference to cardiovascular surgeons and related professionals.

BACKGROUND: Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC. METHODS: A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo. RESULTS: We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA. CONCLUSION Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.
Animals ; Cell Line, Tumor ; Cell Proliferation/genetics* ; China ; Epithelial-Mesenchymal Transition/genetics* ; Mice ; Stomach Neoplasms/genetics*

OBJECTIVE: To investigate the effect of 2-methoxyestradiol (2-ME2) to lymphoma Raji cells and its mechanism. METHODS: Different concentrations of 2-ME2 were used to treat lymphoma Raji cells. CCK8 method was used to detect the effect of 2-ME2 to proliferation of Raji cells. Flow cytometry FITC/PI double labeling method was used to detect early apoptosis of the cells. Western blotting was used to detect the effect of 2-ME2 to the expression of BCL-2, Bax, Caspase-3 and C-myc proteins in Raji cells. RESULTS: 2-ME2 significantly inhibited the proliferation of Raji cells. The inhibition rate increased with the increasing of drug concentration, and increased significantly with the prolongation of drug treatment time (r=0.9215). Flow cytometry FITC/PI double staining showed that the apoptotic rate of 2.5 μmol/L 2-ME2 treatment group was (33.79±1.63) %, while the apoptosis rate of the 48 h group was (51.90±2.72) %, and that of the control group was (7.08±0.36) %. After treated with 2.5 μmol/L 2-ME2 for 12 h, the expression of Bax protein was up-regulated, BCL-2 protein was down-regulated, caspase-3 protein expression was up-regulated, and C-myc protein expression was down-regulated, all of them showed a time-dependent relationship. CONCLUSION 2-ME2 shows obvious inhibitory effect on lymphoma Raji cells in a dose- and time-dependent manner. Its mechanism of treatment on lymphoma Raji cells may be related to up-regulation of Bax/BCL-2 ratio and activation of Caspase-3 to induce apoptosis in cancer cells. Down-regulation of C-myc protein expression also participates in the apoptotic process.
2-Methoxyestradiol ; Apoptosis ; Caspase 3/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lymphoma ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Up-Regulation ; bcl-2-Associated X Protein

Objective: To investigate the histological features and prognostic factors of angioimmunoblastic T-cell lymphoma (AITL). Methods: The pathological data of 62 patients with AITL with complete follow-up information were retrospectively collected and analyzed from Changhai Hospital during September 2012 and September 2017. Histological and immunohistochemical (IHC) examination, in situ hybridization (ISH), and single nucleotide polymorphisms (SNP) gene mutation analysis were done. Subgroup evaluation with histology, IHC, ISH, SNP gene mutation, and association with clinical progression were performed. Results: The cohort included 62 cases of AITL, including 46 males and 16 females patients, with a median age of 64 years. Follicular dendritic cells (FDC) area showed significantly expansion (≥30%) in 40 cases; increased plasma cells (≥10%) was seen in 37 cases; B cells were distributed around blood vessels in 37 cases; and increased p53 mutation positive cells (≥40%) were seen in 39 cases; high Ki-67 index (≥40%) was seen in 39 cases; RHOA mutation was seen in 19 cases; TET2 mutation was seen in 9 cases. Overall survival analysis showed these factors were significantly correlated with tumor prognosis (P<0.05). Multivariate analysis showed that CD38 positive cells<10%, Ki-67≥40%, RHOA and TET2 mutations were risk factors associated with overall survival. Conclusions AITL could be divided into two different prognostic groups, low-grade and high-grade, with statistically significance outcome, based on the FDC area expansion, degree of plasma cell proliferation, B cells distribution pattern combined with gene mutations and clinical progression. Low-grade malignant group progresses slowly, and high-grade malignant group is highly invasive.

OBJECTIVETo investigate the clinical characteristics and outcome of parhents with EBV infection conbined with hemophagocytic syndrome and Hodgkin's lymphoma.

METHODSThe morphotogy of bone marrow cells was observed by bone marrow smear and light microscopy, the pathologic changes of bone marrow ware analyzed by bone marrow biopsy and immunohistochemistry methord, the pathologic changes of lymphonudes ware detected by immunohistochemical methord, the paticnts were treated with ABVD （epirubicin, bleomycin, vincristine and dacarbazine） chemotherapeutic regimen.

RESULTSFever complicatid with pancytopenia, obvious increase of ferritin and sCD25, hypofibrinogenemia, hemophogocytic phenomen of bone marrow, increase of EBV-DNA copy number ware observed, which all accorded with the criteria EBV righted hemophagocytic syndrome. The curative efficacy of amtiinfective treatmatnt was poor, After treatment with HLH-2004 regimen, the fever symptome and the laboratory indicaters such as whole blood cells, ferritin and fibrinogen all were recovered to normal levels. Left mandibular lymphadenctasis was confirmed as Hodgkin's lymphoma （mixed cell type） by pathological examination. The patient achieved complete molecular remission after 1 course chemotherapy with ABVD regimen. The level of EBV-DNA copy number were also decreased. As the reshlt, the patient's hemophagocytic syndrome had bean effectively controlled, and the Hodgkin's lymphoma is still in complete remission.

CONCLUSIONEpstein-Barr virus-ratated hemophagocytic syndrome and Hodgkin's lymphoma are rare, and their long-term prognosis needs to be further explored.

OBJECTIVETo study the clinical characteristics and prognosis of patients with variant Ph chromosome-positive leukemia.

METHODSThe defection of morphology, cytogenetics, immunology and molecular biology was performed in 4 cares of variant Ph chromosome-positive leukemia, and the therepeuitics outcome of 4 patients was evaluated.

RESULTSAmong 4 cases of variant Ph+ leukemia, 3 cases were patients with CML, including 1 case in chronic phase and 2 cases in accelerated phase; and 1 cases was patient with adult B acute lymphoblasric leukemia(B-ALL).The defecfion of cytogenetics in 4 cases showed that 2 cases of CML displayed t(9; 22; 14) abnormality, 1 case of CML displayed t(5; 9; 22) abnormality, moreover, the BCR/ABL fution gane in 3 cases of CML all was e14a2 type, 1 cases of adult B-ALL disylayed t(9; 22; 17) abnormatlity, BCR/ABL fution gene of this case was e13a3 type, 4 patients all received treatment wire chemotherapeptic regimen contaiming methanesulfanate imatinib. As a result, 1 cases of adult B-ALL with e13a3 type BCR/ABL fusion gene positive relapsed after molecular biology remission for 4 months and died in the 10th month; and yet 3 cases of CML are still in molecular biology remission, the disease-free survival time of these 3 cases was 10, 19 and 27 months respectively.

CONCLUSIONThe patients with variant Ph chromosome-positive leukemia will response to the first generation tyrosine kinase inhibitors, but the prognosis of patients with e13a3 type of BCR/ABL fusion gene remains to be further explored.