OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

OBJECTIVE: To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed. RESULTS: Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months. CONCLUSION BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.
Humans ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Leukemia/pathology* ; Hematopoietic Stem Cell Transplantation ; Prognosis ; Myeloproliferative Disorders ; Skin Neoplasms/pathology* ; Acute Disease ; Dendritic Cells

Humans ; Tumor Lysis Syndrome/drug therapy* ; Leukemia, Myeloid, Acute/pathology* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Antineoplastic Agents/therapeutic use*

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.
Humans ; Kidney Neoplasms/pathology* ; Carcinoma, Renal Cell/pathology* ; Diagnosis, Differential ; Angiomyolipoma/diagnosis* ; Biomarkers, Tumor/metabolism* ; Leukemia, Myeloid, Acute/diagnosis* ; Membrane Glycoproteins

Acute pancreatitis is one of the common surgical acute abdominal diseases. Since people first recognized acute pancreatitis in the middle of the nineteenth century, a diversified minimally invasive treatment model with standardization has been formed today. According to the main line of surgical intervention of acute pancreatitis treatment,this period can be roughly divided into five stages:exploration stage, conservative treatment stage, pancreatectomy stage, debridement and drainage of the pancreatic necrotic tissue stage, and minimally invasive treatment as the first choice led by the multidisciplinary team mode stage. Throughout history, the evolution and progress of surgical intervention strategies for acute pancreatitis cannot be separated from the progress of science and technology, the update of treatment concepts and the further understanding of the pathogenesis. This article will summarize the surgical characteristics of acute pancreatitis treatment at each stage to explain the development of surgical treatment of acute pancreatitis,to help investigate the development of surgical treatment of acute pancreatitis in the future.
Humans ; Acute Disease ; Treatment Outcome ; Debridement ; Pancreatitis, Acute Necrotizing/pathology* ; Drainage

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ² test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.
Male ; Female ; Humans ; Retrospective Studies ; Acute Disease ; Treatment Outcome ; Calculi/pathology* ; Lithotripsy ; Pancreatitis, Chronic/pathology* ; Pancreatic Diseases/complications* ; Pancreatic Ducts ; Abdominal Pain/therapy*

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.
Humans ; Hepatitis B virus ; Acute-On-Chronic Liver Failure/pathology* ; Hepatitis B, Chronic ; T-Lymphocyte Subsets/pathology* ; Receptors, Immunologic

Shenfu Injection(SFI) is praised for the high efficacy in the treatment of septic shock. However, the precise role of SFI in the treatment of sepsis-associated lung injury is not fully understood. This study investigated the protective effect of SFI on sepsis-associated lung injury by a clinical trial and an animal experiment focusing on the hypoxia-inducing factor-1α(HIF-1α)-mediated mitochondrial autophagy. For the clinical trial, 70 patients with sepsis-associated lung injury treated in the emergency intensive care unit of the First Affiliated Hospital of Zhengzhou University were included. The levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured on days 1 and 5 for every patient. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to determine the mRNA level of hypoxia inducible factor-1α(HIF-1α) in the peripheral blood mononuclear cells(PBMCs). For the animal experiment, 32 SPF-grade male C57BL/6J mice(5-6 weeks old) were randomized into 4 groups: sham group(n=6), SFI+sham group(n=10), SFI+cecal ligation and puncture(CLP) group(n=10), and CLP group(n=6). The body weight, body temperature, wet/dry weight(W/D) ratio of the lung tissue, and the pathological injury score of the lung tissue were recorded for each mouse. RT-qPCR and Western blot were conducted to determine the expression of HIF-1α, mitochondrial DNA(mt-DNA), and autophagy-related proteins in the lung tissue. The results of the clinical trial revealed that the SFI group had lowered levels of inflammatory markers in the blood and alveolar lavage fluid and elevated level of HIF-1α in the PBMCs. The mice in the SFI group showed recovered body temperature and body weight. lowered TNF-α level in the serum, and decreased W/D ratio of the lung tissue. SFI reduced the inflammatory exudation and improved the alveolar integrity in the lung tissue. Moreover, SFI down-regulated the mtDNA expression and up-regulated the protein levels of mitochondrial transcription factor A(mt-TFA), cytochrome c oxidase Ⅳ(COXⅣ), HIF-1α, and autophagy-related proteins in the lung tissue of the model mice. The findings confirmed that SFI could promote mitophagy to improve mitochondrial function by regulating the expression of HIF-1α.
Humans ; Male ; Mice ; Animals ; Leukocytes, Mononuclear ; Mice, Inbred C57BL ; Lung/metabolism* ; Acute Lung Injury/drug therapy* ; Tumor Necrosis Factor-alpha/genetics* ; Sepsis/genetics* ; Hypoxia/pathology* ; Autophagy-Related Proteins ; Body Weight ; Drugs, Chinese Herbal

Objective To investigate the effects of miR-181b-5p on cells proliferation and apoptosis in acute myeloid leukemia (AML) by targeting paired box 9 (PAX9). Methods The relationship between expression level of PAX9 and prognosis in AML patients was analyzed by gene expression profiling interactive analysis (GEPIA) database and The Cancer Genome Atlas (TCGA) database. Kasumi-1 and AML5 cells were transfected with empty vector (Vector group) or PAX9 (PAX9 group). The proliferation activity was detected by CCK-8 assay, and cells cycle and apoptosis were detected by flow cytometry. Expressions of cyclin-dependent kinase 2 (CDK2), cyclin B1 (CCNB1), B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (BAX) were detected by Western blot analysis. The targeted microRNA (miRNA) by PAX9 was predicted by bioinformatics analysis, and the targeted effect was verified by luciferase reporter assay. The level of PAX9 mRNA was detected by real-time quantitative PCR, and expression of PAX9 protein was detected by Western blot analysis. Kasumi-1 and AML5 cells were transfected with miR-NC (miR-NC group) or miR-181b-5p (miR-181b-5p group). The cells were further transfected with PAX9 (miR-181b-5p combined with PAX9 group) in miR-181b-5p group. The proliferation, cycle and apoptosis of cells were detected by the above methods.Results GEPIA and TCGA databases showed that the expression of PAX9 was down-regulated in AML patients, which was correlated with poor prognosis. In Kasumi-1 and AML5 cells, compared with Vector group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were decreased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were increased in PAX9 group. It was confirmed by double luciferase reporter assay that PAX9 was the target gene of miR-181b-5p. Compared with miR-NC group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were increased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were decreased in miR-181b-5p group. Compared with miR-181b-5p group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were decreased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were increased in miR-181b-5p combined with PAX9 group. Conclusion The miR-181b-5p can promote the proliferation of AML cells and delay apoptosis by inhibiting PAX9.
Humans ; Apoptosis/genetics* ; bcl-2-Associated X Protein ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Leukemia, Myeloid, Acute/pathology* ; Luciferases ; MicroRNAs/metabolism* ; PAX9 Transcription Factor/genetics*

OBJECTIVE: To investigate the efficacy and safety of chemotherapy combined with venetoclax followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). METHODS: The clinical data of 3 patients with BPDCN undergoing allo-HSCT in Department of Hematology, Wuhan First Hospital from July 2017 to November 2021 were collected and retrospectively analyzed. RESULTS: Among the 3 patients, there were 1 male and 2 females, aged 27-52 years old. Skin lesions were observed during initial diagnosis, and it could also be characterized by acute leukemia. Characteristic molecular markers of tumor cells, such as CD4, CD56, CD123, and CD303 were positive. In addition, the expression detection of Bcl-2 in 3 patients were positive. Chemotherapy combined with venetoclax in the initial induction of chemotherapy (1 case) or disease recurrence and progress (2 cases) was performed. There were 2 cases evaluated as complete remission (CR) and 1 case as partial remission (PR) before allo-HSCT. The patients all received a nonmyeloablative conditioning without total body irradiation (TBI). The prevention programme of graft-versus-host disease (GVHD) was antithymocyte globulin + mycophenolate mofetil + cyclosporin A/FK506 ± methotrexate. The number of mononuclear cell (MNC) count was (16.73-18.35)×10⁸/kg, and CD34⁺ cell count was (3.57-4.65)×10⁶/kg. The 3 patients were evaluated as CR after allo-HSCT (+21 to +28 d), the donor-recipient chimerism rate was 100%, and Ⅲ-Ⅳ GVHD was not observed. One patient died at +50 d after transplantation, two patients were followed up for 28 months and 15 months, respectively, and achieved disease-free survival (DFS). CONCLUSIONS BPDCN is a highly aggressive malignant tumor with poor prognosis. Chemotherapy combined with venetoclax followed by allo-HSCT may lead to long-term DFS or even cure. Post-transplant maintenance is still unclear.
Female ; Humans ; Male ; Adult ; Middle Aged ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Acute Disease ; Graft vs Host Disease/prevention & control* ; Myeloproliferative Disorders ; Leukemia, Myeloid, Acute/pathology* ; Dendritic Cells