Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Humans ; Child ; Retrospective Studies ; Thrombocytosis/etiology*

The "student-centered" flipped classroom teaching model can improve students' academic achievement, improve cognition, and cultivate innovation ability. However, it has obvious deficiencies in the integrity and systematization of knowledge as well as education. The traditional teaching concept based on " teacher-centered" has the unique advantages of systematization of knowledge learning and education. Therefore, we integrated the merits of these two different teaching models and introduced the semi-flipped classroom teaching model into the Biochemistry teaching of 2020 stomatology, pharmacy and preventive medicine majors in Cheeloo Medical College, Shandong University, compared with the traditional teaching of 2019 same majors. The data on the improvement of students ' academic achievement and self-cognition were analyzed. The results showed that the students' achievements of the semi-flipped classroom teaching model were better than those of the traditional teaching (P<0. 01). The students' self-cognitions were significantly improved after the implementation of semi-flipped classroom teaching (P<0. 01 or P<0. 05). This study provides a reference for the related teaching and research work in medical colleges.

BACKGROUND: Proteomics is a well studied research method, but its application in the non-surgical treatment of lumbar intervertebral disc protrusion (LIDP) is little reported. OBJECTIVE: To screen the differentially expressed proteins in patients with LIDP but without blood stasis before and after non-surgical treatment by proteomics. METHODS: Sixty patients with LIDP but without blood stasis were selected, and treated with non-surgical treatment for 4 weeks. The differentially expressed proteins were screened and identified by iTRAQ combined with LC-MS/MS. The bioinformatics analysis of the identified proteins was carried out, and the curative effectiveness was investigated. RESULTS AND CONCLUSION: Compared with those before treatment, the Visual Analogue Scale scores were significantly (P ＜ 0.05), the Japanese Orthopedic Association scores were significantly increased decreased (P ＜ 0.05), and the excellent and good rate reached 95.0% post-treatment. A total of 300 differentially expressed proteins were screened and 25 significantly expressed proteins were identified (P ＜0.05). Bioinformatics analysis revealed that nine of the significantly expressed proteins were enriched to 15 KEGG signaling pathways. These results suggest that the use of Western medicine non-surgical treatment for the LIDP without blood stasis can achieve satisfactory results. Besides, complement C1qA, cDNA protein (FLJ60724), complement C4B frameshift mutation, cDNA protein (FLJ53025), mannose binding protein C, apolipoprotein B, hemoglobin α-1 globin chain variant, hemoglobin β subunit and cDNA protein (FLJ76254) may be the potential serum markers of the non-surgical treatment for the LIDP without non-blood stasis.

OBJECTIVETo explore the effect of a self-made guiding needle of steel wire in guiding the wire through the tibial tunnel for the treatment of avulsion fractures of tibial posterior cruciate ligament with open reduction and wire fixation.

METHODSFrom February 2011 to June 2014, a total of 22 patients with avulsion fractures of tibial posterior cruciate ligament underwent surgical treatments were analyzed, including 14 males and 8 females with an average age of 35.6 years old (ranged, 17 to 63 years old). According to Meyers classification, 9 patients were classified as type II, 13 patients were classified as type III. All the patients underwent open reduction and wire fixation with medial knee "L" shape approach. A wire guiding needle was used to guide the wire through the tibial tunnel during operation.

RESULTSWith the assistance of wire guidance needles, wires passed through the tibial tunnel rapidly during the operation in all the 22 patients. All the patients were followed up, X-ray imagings 6 months after operation showed the fractures healed well. The average follow-up time in all patients was 6 months (ranged, 6 to 12 months). The averaged Lysholm knee score in 22 knee was 92.7 +/- 3.4. All patients' posterior drawer test were negative.

CONCLUSIONSelf-made wire guiding needle can simplify the operation procedures in which the wires pass through the tibial tunnel, shorten the operation time, reduce the surgical trauma and complications, and be worthy of clinical application.

Adolescent ; Adult ; Bone Wires ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Posterior Cruciate Ligament ; injuries ; surgery ; Tibia ; injuries ; surgery ; Tibial Fractures ; surgery ; Young Adult

OBJECTIVETo compare the clinical therapeutic effects between ozone and triamcinolone acetonide for the treatment of mild meniscal injury.

METHODSFrom January 2008 to December 2012, 119 patients with meniscal injury diagnosed as type I or II by MRI were divided into three groups. In the triamcinolone acetonide (A) group, there were 38 males and 2 females, with an average age of (25.34 +/- 6.34) years old, ranging from 18 to 48 years old; 36 patients had single knee injuries, 4 patients had double knee injuries and 44 knees with joint effusion. In the ozone (B) group,there were 37 males and 2 females, with an average age of (26.98 +/- 7.20) years old, ranging from 19 to 50 years old; 33 patients had single knee injuries, 6 patiens had double knees injuries and 40 knees with joint effusion. In the combination of ozone and triamcinolone acetonide (C) group, there were 37 males and 3 females,with an average age of (26.44 +/- 6.38) years old, ranging from 18 to 47 years old; 33 patients had single knee injuries, 7 patients had double knees injuries and 39 knees with joint effusion. The patients were treated with injection of 3 mg triamcinolone acetonide alone, 30 ml (30 microg/ml) ozone alone, or both two drugs respectively in knee joint cavity. All the treatment methods were carried out weekly and 4 times injections were required for a treatment course. Knee joint function was evaluated by Lysholm scale and knee joint effusion was examined by MRI before and after treatment.

RESULTSThe scale of knee joint function was 35.68 +/- 4.15 and 65.55 +/- 7.66 in group A, 36.35 +/- 6.83 and 74.39 +/- 8.47 in group B, 36.62 +/- 6.03 and 95.47 +/- 4.78 in group C before and after treatment. Compared with that before treatment, the total scale of knee joint function improved after treatment in every group. The total scale of group C was better than that of the other groups after the treatment,but there was no significant difference between group A and group B. The effective rate of these drugson joint effusion was 68.18% in group A, 62.5% in group B and 87.18% in group C. The effect of co-injection on joint effusion in group C was significantly better than that of triamcinolone acetonide or ozone alone, but the difference between group A and group B was not significant.

CONCLUSIONOzone and triamcinolone acetonide are effective in the treatment of mild meniscal injury, which can relieve symptoms and promote the recovery of joint function. Campared with the single injection, the combination of ozone and triamcinolone acetonide is better.

Adult ; Case-Control Studies ; Female ; Humans ; Knee Injuries ; drug therapy ; Male ; Menisci, Tibial ; drug effects ; Middle Aged ; Ozone ; administration & dosage ; Triamcinolone Acetonide ; administration & dosage ; Young Adult

OBJECTIVETo explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in human GC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells.

METHODSCEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone (Dex). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot.

RESULTSWhen incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR(p-GR), and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein of mTOR (mammalian target of rapamycin).

CONCLUSIONAfter the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.

Apoptosis ; drug effects ; Base Sequence ; Blotting, Western ; Cell Line ; DNA Primers ; Dexamethasone ; pharmacology ; Glucocorticoids ; pharmacology ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Real-Time Polymerase Chain Reaction ; Receptors, Glucocorticoid ; metabolism ; Sirolimus ; pharmacology ; Up-Regulation ; drug effects

Objective To measure the serum growth differentiation factor (GDF15) levels in children with hemophagocytic lympohistiocytosis (HLH),and to explore its possible implications in the development of hyperferritinemia in HLH.Methods Twenty-eight children with newly-diagnosed HLH and 20 age-and-sex matched healthy children were enrolled in this study as research subjects and controls respectively.Serum GDF15 levels were measured by Quantikine ELISA assay (product of R&D Company,USA) according to manufacturer's instructions.Serum ferritin concentration and other biochemical parameters were determined by conventional methods.Comparison of serum GDF15 levels between HLH group and healthy control group were made by nonparametric Mann-Whitney test.Correlations between serum GDF15 concentration and hemobiochemical parameters (Hb,serum ferritin,fibrinogen,blood lipids,and liver and renal function tests) were made via Spearman correlation analysis.Results Serum GDF15 concentration was significantly higher in HLH group than that in healthy control group,with median concentrations and ranges of 1710 ng/L,190-2400 ng/L,and 260 ng/L,104-649 ng/L,respectively (P ＜ 0.001).Serum GDF15 concentration was correlated neither to Hb concentration at diagnosis nor to lowest Hb concentration before HLH-directed chemotherapy.Nevertheless it was positively correlated to serum level of total bilirubin at diagnosis and highest concentration of triglycerates during disease course (x2 =0.475,0.465 ; P =0.011,0.019,respectively),and negatively correlated to lowest levels of fibrinogen and albumin at diagnosis (x2 =-0.423,-0.399 ;P =0.031,0.039,respectively).Serum GDF15 level was not correlated to underlying etiology and mortality rate of children with HLH.Conclusions GDF15 has been documented as an upstream negative regulator of hepcidin,the central iron regulatory hormone produced primarily by hepatocytes,and is massively produced by activated macrophages in an autocrine fashion to suppress further activation of macrophages.This research finding that serum GDF15 level is significantly elevated in children with HLH suggests that GDF 15 is intimately implicated in the modulation of iron homeostasis and the development of hyperferritinemia in HLH.

OBJECTIVETo compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT).

METHODSData of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed.

RESULTSIn the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications.

CONCLUSIONSTo compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

Age Factors ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Length of Stay ; Lung Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Operative Time ; Pneumonectomy ; adverse effects ; classification ; methods ; Postoperative Complications ; etiology ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies ; Smoking ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy ; adverse effects ; methods