Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective To investigate the application value of single detection and combined detection of 4 kinds of inflammatory indicators of procalcitonin (PCT ) ,high sensitivity C-reactive protein(hs-CRP) ,interleu-kin-6(IL-6) and white blood cell(WBC) in diagnosing type 2 diabetes mellitus(T2DM) bloodstream by analy-zing the levels of peripheral blood PCT ,hs-CRP ,IL-6 and WBC in the T2DM bloodstream infection group and T2DM non-bloodstream infection group .Methods The clinical data in 85 patients with T2DM bloodstream in-fection (T2DM bloodstream infection group ) and contemporaneous 80 cases of T2DM non-bloodstream infec-tion(T2DM non-bloodstream infection group) in this hospital from January 2013 to July 2016 were retrospec-tively analyzed .The levels of various inflammatory indicators in peripheral blood were analyzed .The receiver operating characteristic(ROC) curve of various inflammatory indicators was drawn ,the area under the curve (AUC) and the best cut-off value were calculated .The detection schemes included 24 kinds of schemes such as the single indicator ,2-indicator ,3-indicator and 4-indicator .Results The levels of PCT ,hs-CRP ,IL-6 and WBC in the T2DM bloodstream infection group were significantly higher than those in the T 2DM non-blood-stream infection group ,the difference was statistically significant (P<0 .05) .AUC of PCT ,hs-CRP ,IL-6 and WBC were 0 .909 ,0 .818 ,0 .838 and 0 .760 respectively ,with best cut-off values of 0 .493 ng/mL ,11 .19 ng/mL ,40 .95 pg/mL and 11 .87 × 109/L respectively .The Youden index of PCT was highest (0 .65) and the ac-curacy of IL-6 was highest (83 .33％ ) in the single indicator detection scheme .The Youden index and accuracy of the scheme of PCT/hs-CRP and PCT+hs-CRP+IL-6 were highest in the combined detection scheme .Con-clusion PCT detection has the prominent value in the assisted diagnosis of T 2DM bloodstream infection .Inthe combined detection scheme ,PCT/hs-CRP and PCT+hs-CRP+IL-6 have the highest value in the assisted diagnosis in T2DM bloodstream infection .

Objective To explore the effects of steering group model on knowledge of pelvic floor muscle exercise and postoperative discomfort and complications after cesarean section, so as to improve the effect of pelvic floor muscle exercise. Methods A total of 108 patients who underwent cesarean section from August 2015 to August 2016 were randomly divided into experimental group and control group by the random number table method, with 54 cases in each group. The puerperae in the control group were treated with conventional pelvic floor muscle exercise. In the experimental group, the nursing staff and the patients' one-on-one steering group was set up and the individualized pelvic floor muscle exercise was carried out during the hospitalization. The puerperae of the two groups were compared in stress urinary incontinence, pelvic organ prolapse, defecating unfinished feeling, pelvic bulge, lower genital tract discomfort, the level of cognition and behavior of pelvic floor muscle exercise and the puerpera satisfaction in the reexamination after 6 weeks of discharge. Results The number of puerperae with stress urinary incontinence and pelvic organ prolapse in the experimental group was less than that in the control group, and the difference was statistically significant (P< 0.05). The number of puerperae with defecating unfinished feeling, pelvic bulge and lower genital tract discomfort in the experimental group was significantly less than that in the control group (P< 0.05). The score of knowledge level of the pelvic floor muscle in the experimental group was (4.60±1.38), and the exercise behavior score was (4.36±1.17). The score of knowledge level of the pelvic floor muscle in the control group was (2.26±1.27), and the exercise behavior score was (2.57±1.24). The differences were statistically significant (P<0.05). The satisfaction rate was 81.48% in the experimental group and 42.59% in the control group (χ2=5.793,P<0.05). Conclusions The establishment of the steering group for maternal recovery exercise guidance can improve the maternal knowledge of exercise, so as to reduce all kinds of discomfort and complications, improve pelvic floor muscle exercise effect and improve maternal satisfaction.

We investigated the effects of IFN-γ on Chlamydia psittaci (Cps) infection.HeLa cells were treated with different concentrations of recombinant human IFN-γ (5 ng/mL,25 ng/mL,50 ng/mL) after infecting with C.psittaci 6BC,then the number and morphology of C.psittaci inclusion bodies were examined after 48 hours.C57BL/6J mice were intranasally infected with 2 × 106 IFUs C.psittaci 6BC,and intraperitoneally administrated with 10 μg recombinant murine interferon-γ 24 hours prior or post infection,then body weight,activity and survival rate were recorded.The histopathology of mice livers and lungs was analyzed by HE staining on day 5 or day10 post infection.And the chlamydial inclusion bodies were titrated in the lung homogenates of mice sacrificed on day 5 after infection.The inclusion body numbers of recombinant human IFN-γ treated groups (by 5ng/mL,25ng/mL,50ng/mL) were significantly less than that in the control group (23.8±5.1)× 106,(10± 3.58) × 106,(8.0±2.22) × 106,(43.3±11.05)× 106,respectively).And the morphology of inclusion bodies in IFN-γ treated HeLa cells was irregular and much smaller.We also found that IFN-γ could significantly improve the survival rate,reduce acute clinical manifestations and pathological injurery of lung and liver in C.psittaci respiratory tract infected mice model.So we summarized that IFN-γ can mediate strong immunological protection during acute C.psittaci early infection.

Objectives To explore the difference of heart rate deceleration capacity (DC), heart rate acceleration capacity (AC), and heart rate variability (HRV) among overweight children, obesity children, and metabolic syndrome (MS) children. The correlation between body mass index (BMI) and the indexes of DC, AC, and HRV was analyzed. Methods One hundred three overweight and obesity children over 10 years old were selected. The levels of DC, AC, and HRV were detected in these children. Results The level of DC (5.97±1.77 ms) in MS group was lower than that in non-MS group (7.93±1.56 ms); the level of AC (?6.78±1.56 ms) in MS group was higher than that in non-MS group (?8.17±1.61 ms2); the level of HF [335.2(157.03~659.33) ms2] in MS group was lower than that in non-MS group [497.5(345.6~767.1) ms2]; BMI (29.64±2.83 kg/m2) was higher than that in non-MS group (26.79±1.83 kg/m2) and the differences were statistically significant (P all < 0.05). The BMI in overweight and obesity children was negatively correlated with DC (r= ?0.241, P=0.014), and was positively correlated with AC (r=0.199, P=0.044). Conclusions The autonomic nervous function of MS patients is impaired, and the vagus nerve tension is decreased. The protective force on the heart was weaker in the higher degree of overweight, obesity and lower vagus nerve tension, and thus it was the more likely to cause cardiovascular disease.

Objective To explore the relationship between heart rate variability (HRV) and deceleration capacity (DC) in children with idiopathic ventricular premature contraction of different origins. Methods The clinical data from 155 children with idiopathic ventricular premature contraction were retrospectively analyzed. According to the age, the children were divided into young children group (

Objective To investigate the reason and prevention of severe hyponatremia in hysteroscope treatment of the submucous myoma.Method Retrospective study was done on 106 cases of submucous myoma,3 cases with severe hyponatremia after hysteroscope treatment.Results The rate of hyponatremia was 2.8％(3/106),patients appeared nausea and vomiting 1 hour after hysteroscope treatment,blood sodium was lower than 110 mmol/L,volume of distention liquid was 8000-10000 ml,the volume of discharge was 6300-7500 ml.Three patients were treated immediately,1 patient was given sodium lactate Ringer injection and 0.9％ sodium chloride by intravenous drip,and furosemide by discontinuous injection 15 hours later,the hyponatremia was recovery; 2 patients were given 3％ sodium chloride and 15％ potassium chloride by intravenous drip,and furosemide by injection,12 hours later,the hyponatremia were recovery.Conclusion The prevention of severe hyponatremia complication after hysteroscope treatment of the submucous myoma not only need operate carefully but also need take active preventive measures.

Objective To study the effects of light damages of epidermal permeability barrier on cosmetics function evalu-ation.Methods 10volunteers were selected during the1st stage i.e.the3-month experiment of cosmetics function carried out using the traditional method.The skin moisture,transepidermal water loss and skin elasticity were measured,and the required sample size was estimated also.The2nd stage of the experiment of cosmetics function was carried out based on the data of the1st stage.The skin surface was cleaned with the detergent containing sodium lauryl sulfate with mass fraction of5%to induce light damages in skin surface before testing with cosmetics every day,those indexes mentioned above were measured also.Re -sults The1st stage of the experiment using the traditional evaluation method showed that the skin moisture,transepidermal wa-ter loss and skin elasticity revealed significant differences in the3rd month after testing with cosmetics compared with those be-fore testing with out cosmetics(P

The effects of Amrinone (AMR)on left ventricular function in 30 cases of congestive heart failure patients was assessed by M-mode and pulsed Doppler echocardiography. AMR improves the systolic and diastolic function of left ventricle during and after 10 min (AMR lmg ? kg-1, infusion ). The mean stroke volume increased 20% and 18% ; cardiac output increased 23% , 19% ; cardiac index increased 23% and 23% ; ejection fraction increased 32% , 30%; mVcf increased 50% and 48% ; filling velocity in early diastole increased 30% and 21 %; respectively. There were no significant differently between during and after AMR infusion, but there were signifcantly difference a-mong before, during and after AMR infusion. The heart rate changed slightly without statistic significance. The results suggest that AMR could improve the systolic and diastolic function of left ventricle in congestive heart failure patients.

A murine MTEC_1 thymus epithelial cell line established by us has been characterized. The cells were polyhydral and closely packed each other as epithelial like cells. Using anti-keratin antibody, the keratin were shown in cytoplasm of all cells. Under electronmicroscope, bunches of tonofilaments were clearly shown in the cytoplasm, and desmosomes were seen between neighbouring cells. Using anti-mouse epithelial cell monoclonal antibodies for immunohistochemical study, nearly all of the MTEC_1 cells were MTS33 positive. It suggests that MTEC, cells were derived from the epithelial cells located in medulla. The majority of the MTEC_1 cells have normal mouse diploid chomosome number of 40. These results provide evidence that MTEC, cell line is normal murine thymus epithelial cells.