Inhibition of ANGPT2 activates autophagy during hypertrophic scar formation via PI3K/AKT/mTOR pathway

Abstract Background Hypertrophic scar (HS), a fibroproliferative disorder caused by aberrant wound healing following skin injuries such as burns, lacerations and surgery, is characterized by invasive proliferation of fibroblasts and excessive extracellular matrix (ECM) accumulation. The dysregulation of autophagy is the pathological basis of HS formation. Previously, angiopoietin-2 (ANGPT2) was found to be overexpressed in HS fibroblasts (HSFs) compared with normal skin fibroblasts. However, whether ANGPT2 participates in the process of HS formation and the potential molecular mechanisms are not clear. Objective This study is intended to figure out the role of ANGPT2 and ANGPT2-mediated autophagy during the development of HS. Methods RT-qPCR was used to detect ANGPT2 expression in HS tissues and HSFs. HSFs were transfected with sh-ANGPT2 to knock down ANGPT2 expression and then treated with MHT1485, the mTOR agonist. The effects of sh-ANGPT2 or MHT1485 on the proliferation, migration, autophagy and ECM accumulation of HSFs were evaluated by CCK-8 assay, Transwell assay and western blotting. The expression of PI3K/Akt/mTOR pathway-related molecules (p-PI3K, p-Akt and p-mTOR) was assessed by western blotting. Results ANGPT2 expression was markedly upregulated in HS tissues and HSFs. ANGPT2 knockdown decreased the expression of p-PI3K, p-Akt and p-mTOR. ANGPT2 knockdown activated autophagy and inhibited the proliferation, migration, and ECM accumulation of HSFs. Additionally, the treatment of MHT1485, the mTOR agonist, on ANGPT2-downregulated HSFs, partially reversed the influence of ANGPT2 knockdown on HSFs. Study limitations The study lacks the establishment of more stable in vivo animal models of HS for investigating the effects of ANGPT2 on HS formation in experimental animals. Conclusions ANGPT2 downregulation represses growth, migration, and ECM accumulation of HSFs via autophagy activation by suppressing the PI3K/Akt/mTOR pathway. Our study provides a novel potential therapeutic target for HS.

School physician in primary and secondary schools in Yichang of Hubei Province during 2019-2020 / 中国学校卫生

Objective@#To understand school physician in primary and secondary schools in Yichang City, Hubei Province from 2019 to 2020, and to provide a reference for strengthening the school physician team in primary and secondary schools.@*Methods@#149 and 102 primary and secondary schools from 6 municipal districts in Yichang City, Hubei Province, were randomly selected in November 2019 and November 2020, respectively, and were administered by questionnaire survey.@*Results@#The proportion of school physicians increased from 39.6% in 2019 to 65.7% in 2020. In the past two years, the equipment rate of school physician in both central and fringe urban areas increased, especially the fringe urban areas, number of school physician increased from 38 to 96. A total of 93 and 141 school physicians were selected to pariticipate in questionaire survey in 2019 and 2020 respectively. The survey showed that more than 90% of school physicians in primary and secondary schools in Yichang received training, and 74.5% had college education level. However, most of them lack professional qualification and medical background.@*Conclusion@#School physician of primary and secondary of Yichang is well development over the past two years, and the proportion substantially increased. However, there is still room for improvement in the quantity and quality of school physicians, and professional qualification needs to be improved. More attention should be paid to the marginal urban areas to achieve a balance between quantity and quality.

Cone-beam computed tomography evaluation of the distance between the root apex of mandibular molars and the inferior alveolar nerve canal in adults / 口腔疾病防治

Objective@# To evaluate the spatiotemporal relationship between the root apex of mandibular molars and the inferior alveolar nerve canal (IANC) in adults. @*Methods@#Cone-beam computed tomography (CBCT) images were collected in 236 patients, and the distances from the root apexes of mandibular molars to the IANC were measured in NNT 4.6 software. The relationship between distance and gender was evaluated. @*Results@#In two-rooted mandibular first molars, the distances from the mesial root and distal root to the IANC were 7.34 ± 2.07 mm and 6.69 ± 2.08 mm, respectively, in males and 6.47 ± 2.22 mm and 5.94 ± 2.11 mm in females. In three-rooted mandibular first molars, the distances from the mesial root, distobuccal root, and distolingual to the IANC were 7.29 ± 1.30 mm, 7.40 ± 2.33 mm, and 9.97 ± 2.19 mm, respectively, in males and 6.08 ± 2.57 mm, 6.35 ± 2.40 mm, and 9.01 ± 2.90 mm, respectively, in females. In one-rooted mandibular second molars, the distance from the root to the IANC was 4.09 ± 1.64 mm in males and 3.89 ± 1.76 mm in females. In two-rooted mandibular second molars, the distances from the mesial root and distal root to the IANC were 5.14 ± 2.08 mm and 4.39 ± 1.85 mm, respectively, in males and 3.78 ± 1.69 mm and 3.24 ± 1.72 mm, respectively, in females. There were no significant with in-gender differences between the left and right side in the distances from the root apexes to the IANC (P>0.05). The distances from the mandibular first molar were greater in males than in females. The longest average distance was from the distolingual root apexes of three-rooted mandibular first molars to the IANC, and the distances were longer from the distobuccal root apexes of three-rooted mandibular first molars to the IANC than from the distal root apexes of two-rooted mandibular first molars to the IANC (P<0.05). There was no within-gender difference in the distances from the root apexes of single-rooted mandibular second molars to the IANC (P>0.05), but the distances in two-rooted mandibular second molars were larger in males than in females (P<0.05). The distances from the root apexes to the IANC were smaller in mandibular second molars than in mandibular first molars (P<0.05). @*Conclusion @#There are significant differences between adult males and females in the distance from the root apex to the IANC for mandibular first molars and two-rooted mandibular second molars. The distances from the root apexes to the IANC were smaller in mandibular second molars than in mandibular first molars.

Discussion on the management strategy of patients aged over 70 years with esophageal cancer / 中国胸心血管外科临床杂志

@#Esophageal cancer (EC) is the eighth dangerous cancer in the world. As the global population ages, the management of elderly patients with EC poses a challenge as they have many aging-associated diseases and physiological changes. In addition, the data on the tolerability of cancer treatment and the use of combined therapies in the patients to guide their treatment are limited. In this paper, we reviewed the literatures and discussed the effect of surgical resection and the potential complications of elderly patients. We reviewed the basic principles of combined therapy and the potential benefits of chemotherapy or chemoradiotherapy for patients and focused on the management of elderly patients with EC as well as the role of comprehensive assessment for aging to provide treatment options for elderly patients.

Molecular cloning and characterization of a gene encoding RING zinc finger ankyrin protein from drought-tolerant Artemisia desertorum.

A RING zinc finger ankyrin protein gene,designated AdZFP1, was isolated from drought-tolerant Artemisia desertorum Spreng by mRNA differential display and RACE.Its cDNA was 1723 bp and encoded a putative protein of 445 amino acids with a predicted molecular mass of 47.9 kDa and an isoelectric point (pI) of 7.49. A typical C3HC4- type RING finger domain was found at the C-terminal region of the AdZFP1 protein,and several groups of ankyrin repeats were found at the N-terminal region. Alignments of amino acid sequence showed that AdZFP1 was 66% identical to the Arabidopsis thaliana putative RING zinc finger ankyrin protein AAN31869.Transcriptional analysis showed that AdZFP1 was inducible under drought stress in root,stem and leaf of the plant.Semi-quantitative reverse- transcriptase-polymerase chain reaction (RT-PCR) analysis showed that the transcript of AdZFP1 was strongly induced by exogenous abscisic acid (ABA) and also by salinity,cold and heat to some extent.Overexpression of the AdZFP1 gene in transgenic tobacco enhanced their tolerance to drought stress.