Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

【Objective】 To explore the challenging blood cross-matching and resolution for multiple myeloma (MM) patients in different disease stages. 【Methods】 For a patient who was first diagnosed as MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method and tube test. When the major side of cross-matching was agglutinated, the patient’s plasma was cross matched with donors’ red blood cell (RBC) by polybrene test, then plasma dilution cross matched with donors’ RBC by microcolumn gel method. For a patient who was diagnosed as recurrent refractory MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method. 【Results】 1) Case 1 was a first-visit outpatient. The major side of microcolumn cross-match test was agglutinated with the shape of fine line. The result of tube method also showed agglutination of major sides, and the rouleaux were detected by the microscopy. Then polybrene method and microcolumn gel method (after plasma diluted) were applied for cross-matching again with the above two donors’ blood and showed compatibility. 2) Case 2 was a recurrent refractory MM patient. The major and minor sides of microcolumn cross-match test were both agglutinated with the shape of granular. The patient was treated with anti-CD38 monoclonal antibody. The RBCs, after treated with dithiothreitol (DTT) was used to cross match with patient plasma by microcolumn test, and the result was compatible. 【Conclusion】 Polybrene method and microcolumn gel method after plasma diluted are suitable for blood cross-matching of newly diagnosed MM patients, also for those treated with CD38 monoclonal antibody, as the drug interference with cross-matching can be eliminated by DTT.

The infection by Limnodrilus hoffmeisteri Claparède, 1862 (Oligochaeta: Tubificinae) in humans is relatively uncommon. The present report is to describe an incidental human infection with oligochaetes in the nasal cavity of a Chinese man, a 25-year-old man residing in Zhangjiakou city, Hebei province, China presenting with nose bleed, severe itching, continuous sneezing, and rhinorrhea. A lot of oligochaete worms were found in the nasal discharge of the patient. The detected worms were identified as Limnodrilus hoffmeisteri (Annelida: Oligochaeta) based on morphological and molecular characteristics. This incidental L. hoffmeisteri nasal infection is the first case in China and indicates that oligochaete worms can be encountered in humans.
Adult ; Asian Continental Ancestry Group* ; China ; Epistaxis ; Humans ; Nasal Cavity* ; Pruritus ; Sneezing

BACKGROUND: Studies have shown that umbilical cord mesenchymal stem cells are ideal seed cells for tissueengineering research.OBJECTIVE: To isolate, culture and identify tree shrew umbilical cord mesenchymal stem cells, in order toestablish a standardized tree shrew umbilical cord mesenchymal stem cell lines.METHODS: Caesarean-isolated tree shrew umbilical cord samples were used to isolate and culture umbilical cordmesenchymal stem cells using tissue explant adherent method. Flow cytometry assay was used to detect cellsurface markers. Osteogenic and adipogenic induction media were used to induce umbilical cord mesenchymalstem cells to differentiate into osteoblasts and adipocytes.RESULTS AND CONCLUSION: The cultured umbilical cord mesenchymal stem cells expressed CD90 and CD105 with the positive rate of 99.9% and 99.8% respectively. Hematopoietic stem cell marker CD34 expression ratewas 0.0% and the endothelial cell marker CD31 expression rate was 0.7%, in line with the characteristics of umbilicalcord mesenchymal stem cell surface markers. Calcium nodules by alizarin red staining and lipid droplets by oil red Ostaining were observed in the induced cells. These experimental findings indicated that umbilical cord mesenchymalstem cells from tree shrews capable of osteogenic and adipogenic differentiation were successfully isolated and cultured.

Humanumbilicalveinendothelialcells(HUVECs)weretreatedwith3nmol/Lliraglutidefor10, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, and 270 minutes at the concentrations of 5. 5 or 30 mmol/L glucose. Western blot analysis was used to detected protein expression and phosphorylation of insulin receptor substrates-1 ( IRS-1 ) and endothelial nitric oxide synthase ( eNOS ) . The results showed that the baseline level of phosphorylated-eNOS/eNOS was lower in high glucose group than that in normal group(0. 239 ± 0. 016 vs 0. 400 ± 0. 02,P<0. 05). Liraglutide time-dependently increased phosphorylated-eNOS/eNOS and phosphorylated-IRS-1/IRS-1 levels at 5. 5 or 30 mmol/L glucose.

Objective To investigate the effect and mechanism of Imatinib mesilate (Imatinib) on intimal hyperplasia of rabbit carotid arteries after balloon injury. Methods Thirty adult Newzealand rabbits were randomly divided into three groups:group A, B and C. Their right carotid arteries were injuried then administered with 0, 25 or 50 mg/kg of Imatinib dai?ly for 14 consecutive days when the rabbits were sacrificed. The carotid arteries were harvested and sectioned for HE-stain?ing and immunohistochemisty staining. Real-Time PCR was used to examine transcription levels of PDGF-B and PDGFR-βmRNA. The plasma level of PDGF-BB was assayed by ELISA. Results Arterial intimal hyperplasia and stenosis following balloon injury were seen in three groups. Thickness and area of neointima, ratio of thickness of intima to media, ratio of area of intima to media and mRNA level of PDGF-β are all higher in group A than those in group B than those in group C (P<0.01). By contrast, the mRNA transcription level of PDGFR-β increased significantly in group C than that in group A (1.236±0.356 vs 0.708±0.372;t=2.91;P<0.01). Plasma level of PDGF-BB increased in all three groups after balloon injury than that in the baseline (P<0.01). The transcription level of PDGF-BB is higher in group A than that in group B and in group C (ng/L:23.464±3.542, 19.504±2.454, 16.588±1.207, F=17.322, P<0.05). There was no difference between group B and C. There was positive correlation between mRNA transcription level of PDGF-B and plasma level of PDGF-BB ( r=0.806, P<0.01). Conclusion Vascular injury can cause intimal hyperplasia and increased PDGF-B mRNA transcription. Imatinib mesilate could inhibit the intimal hyperplasia through down regulating PDGF-B mRNA transcription.

OBJECTIVE: To study clinical efficacy of surgery after the DCF induction chemotherapy in T2-3 laryngeal carcinoma and hypopharyngeal carcinoma. METHOD: To analyze clinical data about 102 cases of T2-3 laryngeal carcinoma and hypopharyngeal carcinoma retrospectively, 62 cases were divided into experimental group and 40 cases in control group, the experimental group completed three cycles of the DCF induction chemotherapy, then the efficacy was evaluated, surgery were carried out in the end, the control group received operation directly. In two groups, tumor response rates, toxicities, positive surgical margin rates and survival rate differences were observed and compared. RESULT: Tumor response rate was 61.3% in experimental group, the laryngeal carcinoma rate was significantly lower than that in hypopharyngeal (44.4% VS 84.6%, P < 0.05). Compared to its control, there were no significant differences about the positive surgical margin rate, the median survival time, 3-year and 5-year survival rate of laryngeal carcinoma(P > 0.05). The foci edges of 0. 3 cm and 0. 5 cm positive margin rate of hypopharyngeal carcinoma in experimental group were significantly lower than in its control (P < 0.05), but among the 1 cm edge' positive rate, the median survival time, 3-year and 5-year survival rate no significant differences were found (P > 0.05). During induction chemotherapy in the experimental group, no serious adverse reactions were found. CONCLUSION Induction chemotherapy of DCF regimen can not only narrow T2-3 laryngeal carcinoma and hypopharyngeal carcinoma' area, but also ensure an adequate safety margin.
Combined Modality Therapy ; Humans ; Hypopharyngeal Neoplasms ; drug therapy ; surgery ; Induction Chemotherapy ; Laryngeal Neoplasms ; drug therapy ; surgery ; Retrospective Studies ; Survival Rate

Objective To investigate the effect of evidence-based nursing on oral ulcer of leukemia patients undergoing chemotherapy. Methods A total of 60 leukemia patients in our hospital from January 2014 to October 2014 were enrolled as observation group, and given evidence-based nursing intervention including health education, pH adjustment of mouth, mouthwash by ice water, and oral ulcer nursing according to the degree. Clinical data of 60 leukemia patients from April to December 2013 before the implementation of evidence-based nursing( control group) was retrospectively analyzed and the incidence rate and recovery of oral ulcer were compared. Results The incidence rate of oral ulcer in observation group (21. 67%, 13/60) was lower than that in the control group (60. 00%,36/60) (χ2 =5. 964,P<0. 05); the healing time of oral ulcer in the observation group (4.23 ±2.14)d was shorter than that in the control group (7.15 ±2.44)d (t =4. 614,P<0. 05). Conclusions Taking evidence-based nursing in leukemia patients can promote the quality of nursing care, reduce the incidence of oral ulcer, and improve the rehabilitation effect.

Treatment strategies of advanced hepatocellular carcinoma reduce pain,improve quality of life and prolong survival.The latest developments at home and abroad focus on a variety of topical treatments (endovascular treatment,a variety of ablation therapy,radiation therapy) combined with each other and also combined with targeted therapy.In addition,systemic chemotherapy,biological targeting therapy and traditional Chinese medicine have achieved some new progressions.