Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.
Humans ; Myeloid Differentiation Factor 88 ; Disease-Free Survival ; Retrospective Studies ; China/epidemiology* ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Pancreas/pathology* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

Objective: To evaluate diet quality and related problems among children and adolescents in Yunnan Province, in order to provide a theoretical basis for the formulation of targeted dietary interventions for children and adolescents in this region. Methods: Using a stratified random sampling method, 1 078 primary and secondary school students from six prefecture level cities in Yunnan Province were selected from August to November 2022. Dietary quality was evaluated by applying the China Children s Dietary Index (CCDI-2016) on the basis of a 3 d 24 h dietary survey. Results: The total dietary index score of children and adolescents in Yunnan Province was 62.63(54.57,71.19). The overall recommended intakes were largely achieved by consumption of cereals, eggs and sugary drinks, with dietary index scores of 9.91(8.24,10.00), 5.58(0,8.58) and 9.20(7.38,10.00), respectively; there were inadequate intakes of vegetables, legumes, water, vitamin A and dietary fiber, with scores of 5.63(4.09,7.59), 3.48 (0,9.70), 4.23(2.67,5.50), 2.33(1.56,3.53), 3.19(1.63,5.67), respectively; intake of fruits, dairy and aquatic products were severely deficient, with scores of 0(0,1.74), 0(0,2.37), 0(0,9.85), respectively; excessive intake of meat was found, with a dietary index score of 0(0,2.46). The stratified analysis showed that children and adolescents aged 11-13 years had the highest total dietary scores[65.35(54.29,72.03)], followed by those aged 7-10 years[63.46(56.19,72.63)], while the 14-17 year old age group had the lowest scores[59.07(51.15,68.30), H=32.23, P <0.01]. Girls had higher total dietary scores than that of boys[64.20(56.12,72.56), 59.32(52.60,69.72), Z=-5.16, P <0.01], while urban children and adolescents had higher total dietary scores than rural children and adolescents[65.30(54.84,73.62), 62.17(54.31,70.70), Z=-2.11, P <0.05]. Furthermore, higher total dietary index scores were observed among children and adolescents whose parents had a higher educational level( H=27.68, 22.58, P <0.01). The comparison of ethnic groups revealed that the Wa children and adolescents had the highest total dietary index scores, while the Hani children had the lowest( H=27.51, P <0.01). Conclusion The overall dietary quality of children and adolescents in Yunnan Province is not high, the imbalance of dietary nutrition is prominent, and the dietary structure needs to be adjusted and optimized. Intervention programs should focus on the problem of insufficient intake of fruits and vegetables, milk and legumes, aquatic products and excessive intake of poultry meat among children and adolescents.

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
Male ; Adult ; Humans ; Prognosis ; Retrospective Studies ; Myeloid Differentiation Factor 88 ; China/epidemiology* ; Testicular Neoplasms/drug therapy* ; Cyclophosphamide ; Rituximab/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone/therapeutic use* ; Doxorubicin/therapeutic use* ; Vincristine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on lung pathological phenotype and epithelial-mesenchymal transition of alveolar epithelial cells in lung fibrosis model rats caused by paraquat (PQ). Methods Lung fibrosis model was constructed by a single intraperitoneal injection of PQ (30 mg·kg

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Objective:To explore the efficacy and mechanism of Danggui Shaoyaosan on rats of nonalcoholic fatty liver disease （NAFLD）. Method:Sixrty SPF SD male rats were randomly divided into normal group， model group，essentiale （0.144 g·kg^-1） and low， middle and high-dose of Danggui Shaoyaosan groups （2.44， 4.88， 9.76 g·kg^-1）. High fat diet were fed to bulid the NAFLD model， and each treatment group was given corresponding drugs at the same time. After 8 weeks， the serum and liver tissue were collected to detect the contents or activities of total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartic acid aminotransferase （AST）， tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） in serum， the contents of TC， TG and free fatty acid （FFA） in liver tissue， Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to observe the gene and protein expressions of Toll-like receptor 4 （TLR4）， myeloid different factory 88 （MyD88） and c-Jun n-terminal kinase （JNK） and the protein expression of phosphorylation JNK（p-JNK） in liver tissue. Hematoxylin-eosin （HE） staining and Oil red staining to observe the pathological morphological changes of liver. Result:Compared with control group， the contents or activities of TC， TG， ALT， AST and TNF-α in serum， the contents of TC， TG and FFA in liver and the gene and protein expressions of TLR4， MyD88， JNK， and the protein expression of p-JNK in liver tissue of model group were distinctly increased （P<0.01）， the content of IL-10 was significantly decreased （P<0.01）. Compared with model group， the contents or activities of TC， TG， ALT， AST and TNF-α in serum， the contents of TC， TG and FFA in liver and the mRNA and protein expressions of TLR4， MyD88 and JNK， and the protein expression of p-JNK in liver tissue of Danggui Shaoyaosan groups were significantly reduced （P<0.05，P<0.01）， the content of IL-10 in serum of Danggui Shaoyaosan groups was distinctly increased（P<0.05，P<0.01）， HE staining and Oil red staining show that the degree of liver steatosis was alleviated obviously by Danggui Shaoyaosan. Conclusion:Danggui Shaoyaosan has a better treatment on NAFLD by inhibiting TLR4/MyD88/JNK pathway and alleviating the inflammation response.