Objective · To investigate the histone methyltransferase capability of DOT1L-long form and its role in breast cancer metastasis.Methods · The existence of DOT1L-long form was confirmed by PCR, and the mRNA level of DOT1L was tested by real-time PCR. In HEK293T cells in which DOT1L canonical and DOT1L-long were overexpressed respectively, Western blotting was used to test the expression level of DOT1L and the histone methyltransferase capability. In the MCF10A cell line with inducible expression of DOT1L-long, real-time PCR was used to detect the mRNA level of epithelial-mesenchymal transition (EMT) marker, and transwell assay was used to detect the migration of breast cancer cells in which the expression level of DOT1L is low or high. Results · PCR demonstrated the existence of DOT1L-long form, and real-time PCR showed it widely exists in HCT116, T98G, MCF10A cells, etc. Western blotting showed the expression of DOT1L-long form and its H3K79 methyltransferase activity. In MCF10A cells in which overexpressed canonical DOT1L and DOT1L-long, mRNA levels of N-cadherin and fibronectine increased. Transwell showed canonical DOT1L and DOT1L-long both substantially increased the migration of breast cancer cells. Conclusion · The existence of DOT1L-long was confirmed and investigated, which is 202 amino acids longer than the canonical DOT1L, and is coded by a new exon, located between exon 27 and 28. Further, the DOT1L-long has H3K79 methyltransferase activity, and is able to promote breast cancer metastasis.

Adult ; Aged ; Copper ; Hearing Loss, Noise-Induced ; epidemiology ; Humans ; Male ; Middle Aged ; Mining ; Occupational Diseases ; epidemiology

Adolescent ; Adult ; Cities ; Cross-Sectional Studies ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Occupational Exposure ; Occupational Health ; Private Sector ; Sampling Studies ; Young Adult

Objective To investigate the developmental profiles on surface expression and colocalization of NMDA receptor and AMPA receptor on dendritic structures in cultured hippocampal neurons of rats. Methods Two vectors expressing green fluorescent protein tagged GluR1 subunit(GFP-GluR1) and FLAG tagged NR2B subunit(FLAG-NR2B) were co-transfected into cultured hippocampal neurons at 5 days in vitro(DIV5).Surface expressed GFP-GluR1 containing AMPA receptor clusters and FLAG-NR2B containing NMDA receptor clusters were then labeled in living neurons by using anti-GFP primary antibody followed by Alex488-conjugated secondary antibody,and anti-FLAG primary antibody followed by Cy3-conjugated secondary antibody.Furthermore,distribution of the surface clusters was observed on the detailed dendritic structures visualized with co-expression of cyan fluorescent protein tagged actin(CFP-Actin). Results The numbers for GluR1 containing AMPA receptor clusters,NR2B containing NMDA receptor clusters,and colocalized receptor clusters per 100*!?m dendrite in DIV7 and DIV14 neurons were 59.2?5.6 and 74.8?3.1(P

Abstract: Objective　To analyze the epidemiological characteristics of 151 cases of melioidosis and the drug resistance of Burkholderia pseudomallei (BP), in order to provide the basis for diagnosis, treatment and reasonable prevention of melioidosis. Methods　A total of 151 inpatients and outpatients from the Second Affiliated Hospital of Hainan Medical University from January 1, 2013 to August 31, 2022 were collected, and clinical specimens were submitted for examination to isolate and identify BP strains. The clinical data of 151cases of melioidosis and the drug resistance characteristics of pathogenic bacteria were retrospectively analyzed, and using SPSS26.0 software for statistical analysis. Results　Among 151 cases with BP infection, there were 138 males (91.4%) and 13 females (8.6%); the most patients were aged from 45-<60 years old, accounting for 74 cases (49.0%); melioidosis incidence was concentrated in October (19.2%), November (19.2%), August (9.9%) and July (8.6%), and; the number of confirmed cases showed an increasing trend and the time for confirmation was <10 d; Internal medicine system (31.1%), surgery system (26.5%) and intensive care department (20.5%) were the common departments for treating melioidosis; blood (49.0%), sputum (9.9%) and wound secretion (8.6%) were the main clinical specimens for detecting BP; pulmonary infection (68.2%), sepsis (35.1%) and local suppurative infection (23.8%) were the top clinical manifestations in patients with BP infection; the effective rate of treating melioidosis was 74.8%; abnormal liver function was a risk factor for the curative effect of melioidosis (χ2=5.010, P<0.05); the sensitivity rates of BP strains to sulfamethoxazole-trimethoprim (SXT), doxycycline (DOX), imipenem(IPM), ceftazidime (CAZ), amoxicillin/clavulanate (AMC) and tetracycline (TCY) were generally more than 90%, with sensitivities of 98.7%, 97.2%, 96.7%, 94.0%, 93.2% and 90.7%, respectively. Conclusions　It can be concluded that misdiagnosis or missed diagnosis of melioidosis is easy to occur, and the understanding of the epidemiological characteristics and risk factors in this area should be strengthened. The sensitivity of BP to commonly used antibiotics has shown a certain downward trend, clinical use should be standardized, and drug resistance monitoring should be strengthened to improve the efficacy of melioidosis treatment.

Objective To determine the prognostic value of standardized uptake value(SUV)of fluorodeoxyglucose(FDG)by positron emission tomography and computed tomography(PET-CT)in nonsmall cell lung cancer(NSCLC).Methods Forty-eight patients(39 male,9 female)with stage ⅢNSCLC were reviewed.All patients had at least two repeated FDG PET-CT scans either before and after therapy and the maximum standardized uptake value(SUVmax)of the primary lung lesion was calculated. Resuits Of the 45 eligible patients,after a median follow-up of 22.5 months(rang,13 to 35 months),24 patients had local and regional recurrenee or metastasis and 21 remain disease-free.The mean SUVmax of patients who had local recurrence or metastasis before and after treatment was 12.30±3.17 and 5.35±2.29,respectively.The mean SUVmax of patients who had no loeal recurrence or metastasis before and after treatment was 8.46±3.00 and 2.82±0.63,respectively.Significant differences(tbefore=4.15,Pbefore＜0.01;Pafter=4.88,Pafter＜0.01)in SUVmax were observed either before and after treatment.However,the percent change of SUVmax between pretreatment and post-treatment were not significiantly different(t=1.99,P＞0.05).Using the SUVbefore of 9.0 yielded 92% sensitivity,62% specificity,73% positive predictive value and 87%negaffve Dredictive value in predicting regional recurrence or metastasis. While using the SUVafter of 4.3 yielded 71% sensitivity,100% specificity,100% positive predictive valne and 72% negative Dredictive value. Conclusions PET-CT may have the potientials to predict response to therapy and the SUVmax is a significant predictor for recurrent or metastasis in patients of NSCLC.

Objective To evaluate the efficacy and safety of lenalidomide(Len)-based regimens in the treatment to patients with multiple myeloma (MM). Methods Twenty-five multiple myeloma patients who received Len-based regimens were enrolled in this study. There were 5 newly-diagnosed MM patients, 13 relapsed/refractory (rel/ref) MM and 7 MM patients at plateau after treatment. The newly-diagnosed patients received R-PAD regimen, rel/ref MM received R-MD and the patients at plateau(maintenance treatment group) due to more than 2 grade peripheral neuropathy (PN) received Len monotherapy. Results All of the five newly-diagnosed MM achieved complete remission (CR) (100 %) after 2 courses of theatment; of 13 rel/ref patients (76.92 %) achieved overall response, including 3 (23.08 %) achieving CR, 2 (15.38 %) very good partial response (VGPR), 5 (38.46 %) partial response (PR) and the overall response rate was 76.92 %. Two of the other three no response patients had stable disease(SD) and one had progress disease(PO). The seven patients in maintenant treatment group maintained remission in an average follow-up period of 38 weeks and their PN was relieved in various degrees. Conclusion R-PAD regimen is a highly active regimen for newlydiagnosed MM and R-MD regimen is a promising regimen for rel/ref MM, especially for the patients with serious PN; Len may be a good choice as maintenant chemotherapy for the patients with PN.

AIM: To test the effect of ERK1/2 on ischemic preconditioning (IPC) in diabetic rat hearts. METHODS: The diabetic rat model was made with alloxan. After eight weeks, 24 rats were divided into 4 groups: non-diabetic IPC rats (group A); non-diabetic non-IPC rats (group B); diabetic IPC rats (group C); diabetic non-IPC rats (group D). ECGⅡ lead, left ventricular development pressure (LVDP), and first derivative of LVDP ~(?dp/dt_~max ) were recorded. Myocardial phosphorylation of extracellular signal regulated kinases1/2 (ERK1/2) was detected by Western-blotting. RESULTS: (1) The ventricular arrythmia score was significantly lower in group A than that in group C (P

Objective:To investigate the significance of metronomic therapy against Helicobacter pylori (HP) in the prevention of delayed emesis caused by chemotherapy of gastric cancer compared with the routine therapy. Methods:HP infection was confirmed by carbon 14 breath test in 69 patients. Combined chemotherapy was employed for the first time in the patients, who were divided into groups A and B. Metronomic therapy was administered to group A (n=33). Briefly, triplex medication against Helicobacter bacil i triplex was oral y ad-ministered:20 mg of omeprazole and 0.5 g of amoxicillin twice daily, with 200 mg of tinidazole once daily. Oral administration in group A was performed for 14 days from the start of chemotherapy. Simultaneously, 5-HT3 antagonists were applied. By contrast, group B (n=36) was treated with the oral triplex medication against Helicobacter bacilli:20 mg of omeprazole and 1 g of amoxicillin twice daily, with 400 mg of tinidazole once daily. Oral administration in group B was performed for 7 days from the beginning of chemotherapy with simultaneous application of 5-HT3 antagonists. Both groups were simultaneously treated with the 5-HT3 antagonist granisetron at 3 mg once daily during the administration of anti-HP therapy. HP infection was evaluated by immunohistochemistry before and after treatment. Results:The total effective rate for emesis in group A was 84.85%, which was significantly higher than that in group B (55.56%). Among the patients in group A, 15.15%demonstrated delayed emesis, compared with 44.44%of the patients in group B;the number of individuals was significantly lower in group A than in group B. The average number of chemotherapy cycles in group A was significantly higher than that in group B at 3.1 cycles;the difference between groups was statistically significant (P<0.05). In addition, the HP infection in group B was significantly lower than that in group A (P<0.05). Conclusion:Compared with one week of treatment with the conventional dose, two weeks of low-dose metronomic therapy against HP during chemotherapy can significantly reduce chemotherapy induced delayed emesis and can significantly reduce the degree of HP infection in patients with gastric cancer with HP infection.