Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Cell Proliferation ; DNA, Mitochondrial ; Energy Metabolism ; Glucose ; Mouth Neoplasms/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism* ; Phosphatidylinositol 3-Kinases ; Reactive Oxygen Species

Abstract Teen E sports and their negative impact should not be underestimated. The effects of gaming, as an emerging sport, should be examined to determine whether it plays an active role in contributing to the onset of adolescent depression. Therefore, this study outlines the development status of E sports, analyzes the influence of E sports on adolescent depression, and highlights the hidden concerns that E sports pose for the mental health development of adolescents. While taking into account the advantages of E sports and exercise intervention programs, an emphasis should be placed on the prevention of depression, and feasible suggestions and countermeasures should be put forward to promote E sports, while at the same time safeguarding the healthy and orderly development of adolescent mental health.

Objective: To evaluate the shoulder function in patients after repair of head and neck defects with supraclavicular flap. Methods: A retrospective analysis was performed on 56 patients (54 males, 2 females, aged 35-74 years old) who received the repair of head and neck defects with supraclavicular flaps at Department of Otorhinolaryngology Head and Neck Surgery of Beijing Tongren Hospital, Capital Medical University in January 2013-December 2020. The areas and types of flaps, disruption or infections of the incision at the donor sites and other postoperative complications were recorded. Quick disabilities of the arm, shoulder and hand (Quick-DASH) was used for evaluating the shoulder functions in 43 patients conforming to the standard for evaluation of the clinical functions of shoulders and upper limbs, to compare the postoperative upper limb functions between patients treated with clavicular flaps and patients with acromion flaps. Meanwhile, 30 patients who received bilateral neck lymph node dissection over the same period of time were selected for a comparative evaluation of the donor sides (observation group) and the opposite sides (control group). Data were processed with SPSS 22.0. Results: The areas of obtained supraclavicular flaps were (4-10) cm × (10-18) cm. Three patients (5%) showed the defect widths of 8-10 cm at the donor sites, which couldn't be sutured directly, received the repair of their shoulder defects with partial flaps. Defects in other patients were sutured directly. After surgery, 3 patients (5%) suffered from disruption of the acromion incision, which healed after 2 weeks of local dressing. The follow-up time was 6-43 (27±14) months. All patients expressed no dissatisfaction with the appearance. Among 43 patients, 28 (65%) were clavicular type and 15 (35%) were acromion type. The acromion type showed average motor ability and Quick-DASH scores higher than the clavicular type [(average motor ability: (14.4±4.7) vs. (11.8±3.1), t=2.105, P=0.048; Quick-DASH: (16.9±11.6) vs. (12.2±7.1), t=2.284, P=0.033]. Among 30 patients who received bilateral neck lymph node dissection over the same period of time, the observation group showed higher average motor ability, local symptoms and Quick-DASH scores than the control group [average motor ability: (13.4±5.8) vs. (9.8±4.2), t=3.024, P=0.004; average local symptoms: (4.1±1.0) vs. (3.4±1.0), t=2.537, P=0.014; Quick-DASH: (15.6±14.7) vs. (5.2±11.1), t=3.106, P=0.003]. Conclusion: Shoulder dysfunction exists after treatment with supraclavicular flap, which is related to the flap type.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Retrospective Studies ; Shoulder/surgery* ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Treatment Outcome

Mitochondria, as the main site of cell metabolism and energy generation, contains the genome encoding the respiratory chain-associated complexes. Deletions or mutations of mitochondria will lead to mitochondrial respiratory chain deficiencies and these deficiencies play an important role in metabolic reprogramming which is considered as one of the important features of tumorigenesis and development. Many studies have found that tunneling nanotube (TNT), a well-established mitochondrial transfer pathway, is able to restore mitochondrial respiratory deficiencies. This review article focuses on the occurrence of mitochondrial transfer, the mechanism of TNT formation and the promising therapeutic targets acting on mitochondrial transfer.

Objective: We predicted the molecular mechanism of Panax notoginseng in the treatment and improvement of scar hyperplasia, by using the methods of network pharmacology and bioinformatics. Methods: We collected of related active constituents and targets of Panax notoginseng by retrieving TCM systems pharmacology database and analysis platform (TCMSP), and collected of related active constituents and targets of scar by Genecards database and OMIM database. Cytoscape 3.6.1 software was used to construct "drugs-chemical components-targets-diseases" interaction network diagram. The protein in teraction network map (PPI) was constructed by STRING database. The key targets were used to analyze gene ontology (GO) enrichment and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment. Results: Totally 7 chemical compponents, including beta-sitosterol, quercetin, Stigmasterol and etc. and 108 targets, including AKT1, JUN, MAPK1, IL6 and ect. Panax notoginseng exerts its effects on scar mainly by acting on signal pathways, including PI3K-AKt signal pathway, MAPK signal pathway, TNF signal pathway and ect. Conclusions Based on the methodology of network pharmacology, this study preliminarily predicted the major targets and pathways Panax notoginseng in the treatment of scar, providing a direction for further studies.

Objective: To establish an HPLC with charge aerosol detection (HPLC-CAD) method for the determination of kanamy-cin and kanamycin B in kanamycin sulfate injection. Methods: The samples were injected into a Boston Green ODS C18(250 mm× 4. 6 mm, 5 μm) column. The mobile phase was composed of 0. 2 mol·L-1trifluoroacetic acid aqueous solution-methanol (95: 5) , the flow rate was 1. 0 ml·min-1and the column temperature was maintained at 30 ℃. The nebulization temperature for the CAD was maintained at 55℃ and the gas pressure was 56. 4 psi. Results: The linear range of kanamycin was 0. 385-38. 500 μg·ml-1( r=0. 999 9), and the limit of detection was 0. 075μg·ml-1, the limit of quantitation was 0. 154 μg·ml-1, and the average recovery of the method was 100. 97% (n=9). The linear range of kanamycin B was 0. 374-37. 400 μg·ml-1(r=1. 000 0), and the limit of de-tection was 0. 075μg·ml-1, the limit of quantitation was 0. 150 μg·ml-1, and the average recovery of the method was 100. 44% (n=9). Conclusion: The method for the determination of kanamycin and kanamycin B by HPLC-CAD is simple and accurate, the limit of detection is lower than HPLC-ELSD, and the quality of kanamycin sulfate injection can be effectively controlled.

Objective To explore a practical and feasible method for isolation,culture and identification of mouse bone marrow endothelial progenitor cells(EPCs).Methods Bone marrow-derived mononuclear cells isolated by density gradient centrifugation were cultured in endothelial cell growth medium-2 MV medium.Growth and morphological changes of the cells were observed under inverted microscopy.Cell proliferation was observed by cell counting kit-8 assay.Surface markers of the EPCs were detected by flow cytometry.Angiogenic tube formation was determined by Matrigel tube formation assay.Fluores cein isothiocyanat e-ulex europaeus agglutinin-1 (FITC-UEA-1) binding and Dil-Ac-LDL uptake capabilities were observed by fluorescent microscopy.Results In the early stage,the cells were round and spindle-shaped after induced culture for 4 days.After 7 days,the cells grew in colony arrangement and gradually increased in number.After 14 days,the cells were differently shaped,such as short shuttle and triangle.After 21 days,the typical "paving stone" appearance of the cells was observed.The cells were positive for endothelial markers in flow cytometry:CD34 + (84.3％),vascular endothelial growth factor receptor 2 + (74.1％),but CD45 + (4.04％).The cells were capable of forming capillary-like tubes,up-taking Dil-Ac-LDL and binding FITC-UEA-1 in Matrigels.Conclusions A reliable method for isolation,culture and identification of mouse bone marrow EPCs may be improved on the basis of previous experiences.Since the EPCs obtained by this method may be capable of good proliferation,large in number,and stable in biological characteristics,they can serve as ideal seed cells for related subsequent studies.

Objective To investigate the correlation of ERα gene PvuⅡ ,XbaⅠ and ERβ gene RsaⅠ ,AluⅠ digestion polymorphism with coronary atherosclerotic heart disease(CHD) risk factors in Yancheng area .Methods A total of 124 cases of CHD and 163 persons undergoing physical examination served as the CHD group and CON group .The enzyme method was adopted to detect TG and TC .The direction method was adopted to detect HDL and LDL .ERα gene PvuⅡ ,XbaⅠ and ERβ gene RsaⅠ ,AluⅠ digestion polymorphisms were detected by adopting RFLP-PCR .Results The ratios of smoking history ,family history ,complicating hypertension and diabetes ,and the level of body mass index ,TC ,TG and LDLC in the CHD group were significantly higher than those in the control group ,the difference was statistically significant (P＜0 .05) .The various indicators had no statistically difference between male and female(P＞0 .05) .The frequency distribution and geographic distribution of ERα gene PvuⅡ ,XbaⅠ and ERβ gene RsaⅠ ,Alu Ⅰ digestion polymorphisms had no difference between the two groups ,all conformed to Hardy-Weinberg genetic equilibrium and had the group representativeness .pp ,xx ,RR and AA genotypes in the CHD group were maximal ,while PP , XX ,rr and aa genotypes were minimal ;Pp ,xx ,RR and AA genotypes in the CON group were maximal ,while PP ,XX ,rr and aa genotypes were minimal .The distribution frequency of p and x genes in the CHD group was significantly higher than that in the control group ,the difference was statistically significant(P＜0 .05) .Conclusion The estrogen gene polymorphism might be a target spot for effectively treating CHD ,and p and x gene distribution frequency may be related with CHD risk factors .

Objective To observe the changes of bone formation in type 2 diabetes mellitus (T2DM) mice and the effect of different exercises on their cAMP/CREB/Atf4 pathway and bone formation.Methods Forty four-week-old C57BL/6 male mice were randomly divided into a normal control group (ZC) of 10 and a T2DM group of 30.T2DM was induced using the high-fat diet and injection of streptozotocin.Then,the T2DM mice were randomly divided into a T2DM control group (TC),a T2DM swimming group (TS) and a T2DM downhill running group (TD),each of 10.The TS and TD groups were trained for eight weeks as their group names indicated.Then the concentration of cAMP in serum was tested using the enzyme-linked immunosorbent assay (ELISA).The reverse transcription-polymerase chain reaction (RT-PCR) was used to test the mRNA expression of the cAMP-response element binding protein (CREB),activate transcription factor 4 (ATF4),osteocalcin (OC),bone gla-protein (OCN)and bone sialoprotein (BSP) in the left tibia,and Western blotting was employed to test the protein expression of CREB in the right femur.The bone marrow mesenchymal stem cells (BMSCs) were taken and induced to differentiate into osteoblasts (OBs) and dyed using the alkaline phosphatase (ALP) solution.The left side hindlimb bone was taken and scanned the bone mineral density (BMD) of the distal end using the Skyscan Micro-CT.Results Compared with group ZC,the concentration of cAMP declined in group TC.Moreover,the mRNA expression of CREB,ATF4,OC,OCN and BSP as well as the protein expression of CREB of group TC were significantly down-regulated(P＜0.01 or P＜0.05),together with the OB osteogenic capacity and BMD (P＜0.01) compared to group ZC.Compared with group TC,significant increase was observed in the mRNA expression of OC and OCN (P＜0.01 or P＜0.05),as well as the OB osteogenic capacity of group TS.The concentration of cAMP of group TD decreased,the mRNA expression of CREB,ATF4,OC and OCN,as well as the protein expression of CREB were all significantly up-regulated (P＜0.01 or P＜0.05) compared with group TD.The OB osteogenic capacity and BMD(P＜0.05) of group TD also increased significantly.Compared with group TS,the concentration of cAMP(P＜0.05) and the OB osteogenic capacity increased,and the mRNA expression of CREB,ATF4 and OC of group TD increased significantly(P＜0.01 or P＜0.05).Conclusion The bone formation metabolism of type 2 diabetic mice is inhibited.The downhill running is superior to swimming in promoting the osteoblast differentiation and bone formation,as well as the bone mineral density through activating the cAMP/CREB/Atf4 pathway in the bone of T2DM mice.

Objective To explore the clinical therapeutic efficacy and value of endovascular embolization treatment for Hunt-Hess poor-grade intracranial aneurysms. Methods Eighty-seven patients with Hunt-Hess grade Ⅳ - Ⅴ intracranial aneurysrns were treated with endovascular embolization from May 2001 to February 2010,77 patients were grade Ⅳ and 10 patients were grade Ⅴ. Outcomes were assessed by using the Glasgow outcome scale (GOS). Results Follow-up time was from 3 months to 9 years. The therapeutic efficacy was as following according to GOS: 25 patients were grade Ⅰ , 5 patients were grade Ⅱ , 9 patients were grade Ⅲ , 12 patients were grade Ⅳ ,and 36 patients were grade Ⅴ. There were 55.17%(48/87) favorable outcome rate and 28.74% (25/87) mortality rate in all patients. There were 61.70%(29/47) favorable outcome rate and 25.53%(12/47) mortality rate in early stage treatment patients (diseased within 3 d), otherwise there were 47.50% (19/40) favorable outcome rate and 32.50%(13/40) mortality rate in medium and late stage treatment patients (diseased 3 d or later). There were no statistically significance in favorable outcome rate and mortality rate between them (P > 0.05). All the patients were embolized successfully ,technical complications occurred in 8 patients, 10 patients were found angiographic evidence of vasospasm. Conclusions Endovascular embolization is an effective method for treating Hunt-Hess poorgrade intracranial aneurysms. Early stage treatment is a feasible option because it can improve prognosis by reducing rebleeding and vasospasm.