Oncogene c-jun is a member of jun family,the immediately early genes(IEGs),and belongs to one of the nuclear transcription factors of basic leucine zipper(bZIP)family.Combined with many gene promotors,c-jun is involved in the regulation of gene transcription.Its products play important roles in regulating gene expression,cell proliferation,differentiation and apoptosis.The structure,biological funetion,regulation of c-jun and its roles contributing to tissue damage are reviewed in this article,which may provide understanding for severity of tissue injury and wound age estimation in the field of forensic pathology.

BACKGROUND:Distraction osteogenesis is one of the most important tissue engineering technologies. However, the exact signaling pathway controling mesenchymal stem cel-osteoblast lineage (MSC-OB) migration during distraction osteogenesis has not yet been elucidated. More efforts should be paid to make a ful understanding of the mechanism on MSC-OB lineage migration, which can improve the clinical efficacy of distraction osteogenesis.
OBJECTIVE:To evaluate the effects of mechanical stretch on the ability of MSC-OB mobility and expression of mammalian target of rapamycin (mTOR) signaling pathway as wel as matrix metaloproteinases (MMPs) in MSC-OB, and to make clear the mechanism by which controls MSC-OB migration during distraction osteogenesis.
METHODS:Twelve Sprague-Dawley rats were randomized into two groups: experimental group (n=6), anin vivo rat mandibular distraction osteogenesis model was established on the right side of rats; non-stretch group (n=6), only the mandibular resection was done but with no distraction osteogenesis. Immunohistochemical staining was used to detect phosphorylated mTOR expression in new osteotylus at 15 days after operation. In addition, an in vitro cel stretch model was made in the mandibular mesenchymal stem cels from healthy Sprague-Dawley rats under resting tension force (6%, 4 hours); no distraction was done in control group. The ability of MSC-OB mobility, the expression of mTOR, Raptor, p70S6K and MMPs were evaluated using experiment methods including immunohistochemistry staining, real-time PCR and scratch assay.
RESULTS AND CONCLUSION: The expression of phosphorylated mTOR in MSC-OB was upregulated in the mandibular bone calus of the stretch group than the non-stretch group (P < 0.05). In thein vitro experiments, MSC-OB applied with mechanical stretch (6%, 4 hours) showed elevated gene expression levels of mTOR, Raptor, p70S6K, MMP-2, MMP-9 and MMP-13 compared with the control group (0%, 4 hours). Meanwhile, MSC-OB in the experiment group (6%, 4 hours) showed a greater ability of mobility, as demonstrated by a farther distance after 48 hours of observation (P < 0.05). The present study suggests that the enhancement of MSC-OB mobility correlates with increase of the gene expression of MMPs and mTOR signaling pathway. Mechanical stretch may promote MSC-OB migration through activation of mTOR/MMPs signaling pathway.

Objective To research the effect of regulating systemic inflammatory response by using ulinastatin in elderly patients after sevoflurane inhalation of postoperation cognitive function. Methods 60 patients under went elective abdominal surgery, were randomly double-blinded divided into 2 groups. Every group had 30 patients.Group A accepted continuously intravenousiy infusion ulinastatin 2000 units · kg-1 · h-1 , while group B got equivalent continuously intravenous infusion 0.9% sodium chloride injection. The time point of opening eye, extubation, response and the mini-mental state examination(MMSE) score on different time points were observed. Meanwhile, the changes of concentration of hs-CRP, IL-6,IL-10 were measured. Results Compared with two groups,group A has shorter time on response(F =4.399,P = 0.040). Two both groups had decrease of MMSE score 1 hour after surgery compared with preoperation(t =7. 732,11. 916, both P ＜ 0.01), and the score were less than the preoperative value of more than 2 points which showed cognitive decline in patients. But group A's rate of decline in MMSE score was lower than group B(F = 7. 582 ,P =0.012). Both groups had the MMSE score decline 6h after surgery (t = 4. 606,8. 615, both P ＜ 0.05). Group A's score was less than the preoperative value for less than 2 points, group B's score was lower than the preoperative value for more than 2 points, but the difference between the two groups was not significant (P ＞0. 05). Both groups had higher concentrations of hs-CRP、IL-6 、IL-10 at postoperative 1 d ,3d ,7d (all P ＜ 0.01), peaked at postoperative 1 d, and hadn't come back to the preoperative level 7d*after surgery. In group A, the concentrations of hs-CRP, IL-6 increased (postoperative 1 d,3d), but the rate was lower than the group B (F = 14. 885, P = 0.000;F = 4. 405, P = 0. 040; F = 18. 204, P = 0.000; F = 8. 074, P = 0. 006); while the increased rate of concentration of IL-10 was higher than the group B(F=5.197,P=0.026;F= 12.236,P =0.000). Conclusion Ulinastatin could promote the elderly after sevoflurane inhalation rapid recovery of cognitive function, which may be related to the regulation of systemic inflammatory response.

Objective To improve the knowledge of the diagnosis and treatment of functional insulinoma. Methods The clinical data of 12 cases of functional insulinoma in China-Japan Union Hospital of Jilin University from 2000 to 2009 were analyzed retrospectively. Results For the 12 cases of functional insulinoma, preoperative fasting blood glucose and the positive rate of insulin were 92% and 89% respectively. The positive rate of IRI/G and C-Peptide reached 100%. The accuracy of the niveau diagnosis of preoperative abdomen ultrasound, CT and of MRI were 75%, 36% and 0% respectively; whereas the accuracy of localization of intraoperative palpation combined with ultrasonography reached 100%. The result of glucose increased by one time within one hour after excision and the rest excision. In the 7 follow-up cases, the symptom of hypoglycemia was not found. There were 3 cases of pancreatic fistula after operation. Conclusions For the suspected cases of functional insulinoma, the measurement of IRI/G and C-Peptide are needed besides measuring blood glucose and insulin. Intraoperative palpation and ultrasonography are effective methods of the localization of functional insulinoma. The complete resection of the insulinoma can be assessed by monitoring the change of the blood glucose after excision as well as the rapid intraoperative pathological examination.

Objective To explore the significance of interleukin -35 (IL -35)in serum of patients with severe hepatitis.Methods Collected 39 cases of chronic hepatitis B(CHB)patients and severe hepatitis,and col-lected 19 cases of healthy control's(HC)peripheral blood at the same time.ELISA method was used to detect IL -35 levels.Results IL -35 in CHB and severe hepatitis group [(483.5 ±280.7)ng/mL and (277.9 ±248.7)ng/mL] were higher than HC group (50.5 ±47.8)ng/mL(t =2.089,3.303,P =0.044,0.002).In severe hepatitis group, the IL -35 levels in survivors group (305.3 ±301.2)ng/mL was higher than death group (78.7 ±33.2)ng/mL (P =0.012).IL -35 was positively correlated with ALT and AST,the correlation coefficient were 0.649 and 0.599. Conclusion IL -35 is involved in the pathogenesis of hepatitis B process,the low serum IL -35 levels in severe hepatitis patients may herald a bad prognosis.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

BACKGROUND: Over the last 10-20 years, international guidelines and consensus statements for the management of common allergic diseases (e.g. allergic rhinitis and asthma) have been developed and disseminated worldwide. However, their impact on knowledge and standard of clinical practice among primary care physicians and specialists is unknown. OBJECTIVE: To investigate need for an improvement in the dissemination of international guidelines for the diagnosis and management of allergic rhinitis. METHODS: Seven medical students who attended 3-day 1st International Basic Allergy Course (2010) took down all questions raised during the entire course. A systemic analysis of these questions was performed to identify areas for improvement in diagnosis and management of allergic diseases mainly in the Association of Southeast Asian Nations (ASEAN) region. RESULTS: 268 participants, 143 males and 125 females, comprising Ear, Nose and Throat (ENT) specialists (n = 106) and trainees (n = 34), general practitioners (n = 87), and other healthcare professionals (n = 41) attended the course. Of the 103 questions recorded, 59 were regarding treatment modalities in allergy practice such as immunotherapy (n = 38), pharmacologics (n = 15), nasal surgery (n = 2), and others (n = 4). 41 questions (39.8%) have answers based in the Allergic Rhinitis and its Impact on Asthma guidelines (2001 and 2008). Certain questions were selected for further analysis because they appeared to be (a) more commonly asked (e.g. immunotherapy) or (b) were deemed to be challenging or, even controversial (e.g. food allergy and differential diagnosis between vasovagal and anaphylaxis reaction), as the recommendations in current international guidelines were less well-defined. CONCLUSION: Our study identified several problems that, if tackled, could help minimize confusion and provide better care for patients suffering from allergic diseases especially in the ASEAN region.
Anaphylaxis ; Asian Continental Ancestry Group ; Asthma ; Consensus ; Delivery of Health Care ; Diagnosis ; Diagnosis, Differential ; Ear ; Female ; Food Hypersensitivity ; General Practitioners ; Humans ; Hypersensitivity ; Immunotherapy ; Male ; Nasal Surgical Procedures ; Nose ; Pharynx ; Physicians, Primary Care ; Rhinitis, Allergic ; Specialization ; Students, Medical

Objective:To design a modified S1PR3 specific agonist, GPS-725.017, and investigate its protective effect on acute lung injury by promoting macrophage clearance of bacteria.Methods:A short peptide derived from the intracellular region of S1PR3 receptor was named GPS725.017, which was modified with norleucine (Nle) and myristicacid (myr) at its N terminus. Mice were divided into the sham operation group, solvent group and GPS-725.017 treatment group. The acute lung injury model was induced by endotracheal injection of E. coli (5×10 6 CFU), and the experimental group was treated with GPS-725.017 (10 mg/kg). The 48-h survival rate of mice was recorded. After 5 h of modeling, the bacterial load and inflammatory cytokines in peripheral blood and lung were detected, and Vps34 protein content in alveolar macrophages was determined by Western blot. After 12-h of modeling, lung tissues were collected for H&E staining and pathological scores. Results:Compared with the solvent group, the survival rate of mice in the GPS-725.017 treatment group was significantly improved ( P<0.01), the bacterial CFU in blood and alveolar lavage fluid was significantly lower than that in the solvent group ( P<0.001), and the levels of TNF-α and IL-1β in blood and alveolar lavage fluid were significantly lower than those in the solvent group ( P<0.001). Western blot showed that the expression level of Vps34 protein in alveolar macrophages was significantly higher than that in the solvent group ( P<0.01). Histopathology result showed that the pathological damage of lung in the treatment group was significantly less than that in the solvent group ( P<0.001). Conclusions:The modified synthetic S1PR3 specific agonist GPS-725.017 could specifically activate the S1PR3 receptor on the membrane of alveolar macrophages and up-regulate the expression level of intracellular Vps34 protein, which can promote the removal of bacteria in alveolar macrophages, significantly reduce the degree of lung injury and improve the survival rate in ALI mice.

Objective:To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC).Methods:The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 μg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ 2 test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results:The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter ( r2=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter ( r2=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP ( P<0.01) . Conclusions:PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.

Objective:To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC).Methods:The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 μg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ 2 test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results:The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter ( r2=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter ( r2=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP ( P<0.01) . Conclusions:PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.