Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

Objective To study the changes of volatile oil of Atractylodis Rhizoma(AR)and Atractylodis macrocephalae Rhizoma(AMR)before and after co-decocting in different proportions(1∶3,1∶2,1∶1,2∶1,3∶1).Methods The volatile oil was extracted by steam distillation and analyzed by gas chromatography-mass spectrometry(GC-MS).Results After co-decocting,the yield of volatile in each group was higher than in single decocting.The relative contents of most components in the mixed volatile oil after co-decocting were significantly different from the theoretical calculation.Co-decocting could promote the extraction of hinesol,which is the main component of the essential oil of AR,and the compatibility with large doses of AMR(1∶2 and 1∶3)could also promote the dissolution of β-eudesmol.At the same time,the extraction of atractylon,germacrene B and valencene was inhibited by co-decocting,which were the main constituents of the volatile oil of AMR.Conclusion Co-decocting of AR and AMR could improve the extraction rate and change the chemical composition of volatile oil.After co-decocting,the dissolution of active components of AR increased,while the dissolution of active components of AMR decreased.It may lead to the change of pharmacological activity.

Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Coprococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

Acute aortic syndrome(AAS) is a lethal disease with acute onset and a high mortality rate as well as a higher incidence rate especially in an aging population. The diagnostic techniques of AAS have been improving in recent years. Many serum biomarkers have been shown to have the potential of further clinical implication. Advancement of imaging techniques has also improved the accuracy of early diagnosis. Although traditional treatment modality involving open surgery is life-saving, it still has a high mortality rate and a high major morbidity rate. The increasing utilization of endovascular techniques has greatly improved the prognosis of AAS, while it still need further optimization to be applied in different subgroups of patients.

Objective To study the clinical effect of specific immune therapy for children with allergic rhini-tis(AR)and its influence on the level of serum IL -17 and IL -35.Methods 174 children with AR were chosen as the research group,who were used specific immune therapy for 24 months.In same period,110 cases of healthy chil-dren were selected as the control group.Curative effect was evaluated by rhinitis symptoms total score(TRSS)points rate.quality of life was evaluated by nasal conjunctivitis related quality of life questionnaire(RQLQ)score.Pulmonary function before and after treatment,serum Eos counting,IL -17,IL -35 were detected.Results (1 )In research group,the total effective rate after treatment of 2 years was 89.66%,which was significantly higher than 71.26% after treatment of 1 year,there was statistically significant difference(χ2 =18.716,P <0.05).(2)In the research group, TRSS score and RQLQ score after treatment of 1 year and 2 years were lower than that before treatment(t =28.360, 42.850,7.749,42.850,all P <0.05 ),and the data after treatment of 2 years were less than that after treatment 1 year(t =19.207,10.558,all P <0.05).(3)In the research group,FEV1 /predictive value after treatment of 1 year and 2 years elevated compared to that before the treatment,the airway resistance value /forecast and Eos count were lower than that before the treatment(t =15.972,27.811,48.780,62.211,10.930,62.211,all P <0.05).FEV1 /pre-dicted value after treatment of two years was higher than that after treatment of 1 year,airway resistance value /forecast and Eos counts were less than that after treatment of 1 year(t =8.728,14.707,16.488,all P <0.05 ).(4)In research group,serum IL -17 after treatment of 1 year and 2 years reduced,while IL -35 rose (t =9.162,14.522, 10.235,14.522,all P <0.05).And IL -17 after treatment of 2 years was lower than that after treatment of 1 year,IL-35 was higher than after treatment of 1 year(t =5.795,7.731,all P <0.05).(5)Correlation analysis showed that the serum IL -35 and the level of IL -17 showed a negative correlation(r =-0.36,P <0.05).Conclusion Effect of specific immune treatment on children with allergic rhinitis is better,specific immune treatment can improve the clinical symptoms,inhibit IL -17,promote IL35 and improve lung function and quality of life of patients.

Objective To improve the quality of the clinical hematologic examination laboratories in national free preconception health examination project by using randomized blind sample test in the external quality assessment (EQA ) schemes .Methods Blind samples for clinical hematologic examination were prepared as higher ,middle ,lower three levels .Samples were dispensed in u‐nified way which included 4 times conventional EQA and in random way which included 1 time blind sample test .Samples will be tested by Clinical hematologic examination laboratories in national free preconception health examination project .The feedback re‐sults were summarized and analyzed by EQA organizer .Results In 4 times of conventional EQA ,the rates of accepted score of 134 laboratories were 72 .4% ,97 .8% ,97 .0% and 98 .5% respectively .The rates of accepted score in last three times were statistically significant higher than that in the first time(P<0 .05) .However ,the rates of accepted score (84 .3% ) in randomized blind sample test were significant lower than that(97 .0% ) in conventional EQA which was conducted at the same time(P<0 .05) .Conclusion The use of randomized blind sample test may help the EQA organizer to find the problems in laboratories participated EQA and find effective way to improve the quality of the laboratories .

Objective To investigate the prognosis correlation factors of sudden hearing loss.Methods A retrospective analysis was performed in 137 cases (149 ears) of sudden hearing loss.The relationships between the age,prehospital delay time,type of hearing loss,degree of hearing loss,and whether with dizziness,tinnitus,diabetes mellitus,high blood pressure and therapeutic effect were observed.Results The total effective rates in ＜ 45 years,45-59 years and ＞ 59 years patients were 86.36％(38/44),77.78％ (56/72) and 57.58％ (19/33) respectively.There were statistical differences in the total effective rate between ＜ 45 years,45-59 years patients and ＞ 59 years patients (x2 =8.128,P =0.004; x2 =4.525,P =0.033).The total effective rates in patients who were treated ≤7 d,8-14 d and ≥ 15 d were 83.52％ (76/91),76.67％(23/30) and 50.00％(14/28) respectively.There were statistical differences in the total effective rate between patients who treated ≤7 d,8-14 d and patients who were treated ≥ 15 d (x2 =13.050,P =0.000; x2 =4.459,P =0.035).The total effective rates in low-mid frequency type,all frequency type,total deafness type and mid-high frequency type were 89.66％ (52/58),84.44％ (38/45),7/12,47.06％ (16/34) respectively.There were statistical differences in the total effective rate between low-mid frequency,all frequency type and total deafness type,mid-high frequency type (P ＜ 0.05).The total effective rates in hearing loss mild degree,middle degree,severe degree,extremely severe degree and total deafness were 87.23％ (41/47),86.11％ (31/36),61.90％ (13/21),7/15 respectively.There were statistical differences in the total effective rate between mild degree,middle degree and severe degree,extremely severe degree and total deafness (P ＜ 0.05).The hearing loss prognosis with the dizziness,diabetes mellitus,high blood pressure was worse.Conclusions It is considered that the age,prehospital delay time,type of hearing loss,degree of hearing loss,and whether with dizziness,high blood pressure,diabetes mellitus are related to the total effective rate.The prognosis of hearing loss can be estimated according to these correlation factors.

Background and objective hTis study aims to explore the effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) on the lymphangiogenesis of lung cancer withEGFR mutation, as well as to determine the function of EGFR targeted therapy in relation to the inhibition of lymphangiogenesis during lung cancer treatment.Methods hTeEGFR double mutant lung cancer cell line NCI-H1975 is used to construct lung cancer xenogratf models. hTe models are divided into two groups:the solvent control group and the EGFR-TKI treatment group. Each group includes ifve mice. hTe inhibitory effect of EGFR-TKI on the growth of transplanted tumors was observed. Immunohistochemical method and lymphatic endothelium speciifc antibody D2-40 were used in the experiment to observe the inlfuence of EGFR-TKI on lymphangiogenesis in lung cancer.Results hTe weight and relative volume of tumors in the EGFR-TKI treated group were less than those in the solvent control group. hTe average lymphatic ves-sel density of EGFR-TKI-treated mice was 6.44 per case. hTis value was 10.70 per case in the solvent control group. Lower density of lymphangiogenesis was found in the EGFR-TKI treated group (P=0.023). hTe area and longest diameter of neonatal lymphatic vessel of the EGFR-TKI treated group were less than those of the solvent control group. Moreover, EGFR-TKI exhibited no signiifcant effect on the invasion of tumor cells into the lymphatic vessel (P=0.519).Conclusion EGFR-TKI can inhibit lymphangiogenesis inEGFR mutant lung cancer while suppressing vessel diameter and expansion area.

Objective To evaluate the effects ofbeta-endorphin (β-EP) and substance P (SP)with sedative and analgesic drugs on mechanical ventilated patients. Methods Twenty-eight mechanical ventilated patients were randomly divided into two groups: midazolam group (M group, 14 cases) and midazolam combined with fentanyl group (M + F group, 14 cases). Eight healthy persons were as control group (C group). The sedative target was VAS≤3 scores and Ramsay 2-4 scores. The levels of serum β -EP and SP were tested before sedation and 12, 24 h after sedation in mechanical ventilated patients and at 8 Am in C group. The sedation levels were evaluated and the hemodynamie and respiratory parameters were recorded before sedation and 1, 12, 24 h after sedation in mechanical ventilated patients. The oxygenation index was measured before sedation and 1,12, 24 h after sedation. Results The levels of serum β -EP and SP in M and M+F group were significantly higher than those in C group(P< 0.05). After sedation, the level of SP in M+F group [(101.42 ± 12.46) ng/L]was significantly lower than that in M group [(132.72 ± 23.82) ng/L] (P < 0.05). Compared with before sedation, there were significant differences in heart rate, VAS and Ramsay scores between M group and M+F group (P< 0.05). Compared with M group, pressure airway and respiratory rate at 12, 24 h and total after sedation were lower in M+F group (P <0.05). The amount of serum SP in mechanical ventilated patients. Fentanyl improves the ventilator synehron and reduces the dose of midazolam.

Objective:To Observe the effect of recombinant tissue-type plasminogen activator (rt-PA) in treatment of acute myocardial infarct.Methods:Two groups of patients were observed.The subjects in the control group (35 patients) were treated with routine intervention,while those in thrombolysis group (15 patients) were treated with rt-PA in addition to the routine intervention.Results:There is a better outcome in the thrombolysis group as compared with that in the control group,in terms of length of angina relief,degree and length of EKG changes as well as the time for serum enzyme changes.The mortality rate in the thrombolysis group was significantly lower than that in the control group (P＜0.01).Conclusion:The rt-PA for thrombolysis in acute myocardial infarct patients can reduce the infarct size and improve the cardiac function rapidly as well as increase the survival rate.