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.

Background Doxycycline is a broad spectrum antibiotic,and it is frequently used in the treatment of ocular surface diseases.Objective The purpose of the present study was to investigate the effect of doxycycline on the inhibition of cell proliferation in bovine corneal myofibroblasts in vitro and assess its contribution to ocular surface repairing mechanism.Methods Six fresh bovine corneas were collected.The corneal stromal layer was isolated by two-step method of 1.0 g/L and 2.0 g/L collegenase-1.Isolated cells were plated at mantaryay culture flask in 10％ FBS of RPMI-1640.Vimentin and alpha-smooth muscle actin (α-SMA) organization were evaluated by immunocytochemistry,and the cells with influoresccence staining for vimentin and α-SMA were identified as the corneal myofibroblasts.Doxycycline at the concentrations of 10,20,40,60,80 mg/L was added to the medium,respectively,in different concentrations of doxycycline groups.Dexamethasone (120 mg/L)was used in the same way in the positive control group,and no drug was used in the negative control group.Cell proliferation was evaluated by MTT and the cell cycle was analyzed by BD FACScan flow cytometer assay 24 hours and 48 hours after addition of any drug.Results The cells grew well and showed the positive response for vimentin and α-SMA.MTT assay showed that the A570values of bovine corneal myofibroblasts were gradually declined with the increase of the concentration of doxycycline and lapse of active time,showing statistically significant difference (Fconcentration =1233.778,P＜0.001 ; Ftime =227.564,P ＜ 0.001).And the difference between the two factors was also statistically significant (Ftime*concentration =51.656,P＜0.001).Flow cytometry cell cycle analysis showed that 24 hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.85％,84.36％,85.18％,87.12 ％ and 89.31％,showing significant increase in comparison with 63.89％ of the negative control group (all P＜0.05),and that of 40 mg/L doxycycline group was near the positive control group.Forty-eight hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.78％,86.15％,88.23％,89.57％,93.00％,with significant increase in comparison with 70.17％ of the negative control group (all P ＜ 0.01),and that of 40 mg/L doxycycline group was near the positive control group.Conclusions The growth of the bovine corneal myofibroblasts is inhibited by doxycycline in time-and dosedependent manner in the range from 10 mg/L to 80 mg/L,and 40 mg/L of doxycycline has an obviously inhibitory action as 120 mg/L dexamethasone.

Objective In order to know the effect of heating infusion for premature infants to pro-mote their restoration of physiological function. Methods Divided 160 premature infants who need infu-sion into the experimental group and the control group randomly, there were 80 cases in each group. Normal temperature infusion was used in the control group, while heating infusion was used in the experimental group, compared the body temperature, pluse, respiration, blood pressure, oxygen saturation and the blood ghcose between the two groups. Results There were significant difference about the indexes which had mentioned above between the two groups. Conclusions Heating infusion can effective promote the reha-bilitation of physiological function of premature infants.

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.

Objective To retrospectively analyze the outcomes and adverse effects of sequential therapy of BTD and MPT regimen for the newly-diagnosed multiple myeloma patients no eligible for high dose chemotherapy and stem cell transplantation. Methods Thirty-six patients were involved in this study and the patients were treated with tandem therapy of BTD and MPT regimen. The patients were treated with BTD regimen as induced therapy no less than 2 cycles. When the patients got PR or above PR,they were treated with MPT regimen as consolidation therapy which was no less than 2 cycles. Then,the patients who achieved PR or partial PR were received MPT chemotherapy regimen as consequent treatment. After that,low dose thalidomide was used as maintenance therapy. The outcomes and adverse effects were retrospectively evaluated. Results Thirty-six patients were treated with BTD regimen as induced therapy. The results were that 7 patients (19.4 %) achieved CR,8 (22.2 %) VGPR,14 (38.9 %) PR and the OR rate was 80.6 %. The patients (n=29) who achieved no less than PR was treated with MPT regimen as consequent therapy. The results were that four patients were in progression and the others were stable. Twenty-five patients were treated with low dose thalidomide as maintenance therapy. The median progression-free survival (PFS) did not reached yet until last follow-up (median follow-up time was 16.5 months). One-year overall survival rate was expected 86.0 % and 3-year expected overall survival rate was 77.0 %. The main regimen-associated toxicities included thrombocytopenia,peripheral neuropathy (PN),Herpes Zoster,gastrointestinal symptoms,anemia,neutropenia,constipation,fatigue,rash and so on. The incidence of grade 3 and 4 adverse events was low. Conclusion Sequential therapy of BTD and MPT regimen can be used as the front-line therapy for the newly-diagnosed multiple myeloma patients no eligible for high dose chemotherapy and stem cell transplantation.