The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective:To fabricate the composite scaffolds for bone regeneration with silk fibroin (SF), bacterial cellulose nanofibers (BCNR) and hydroxyapatite (HAp) and evaluate their osteogenic activity.Methods:HAp particles, BCNR and bone morphogenetic protein-2 (BMP2) were added into SF aqueous solution in turn, poured into molds of different sizes after being mixed evenly and processed at -25 ℃ for 24 hours to obtain frozen molds, and the composite scaffolds were frozen-dried by freezing-drying machine. The composite scaffolds with different mass ratios of SF and BCNR were divided into groups A (2∶1), B (4∶1) and C (6∶1), and the inactive composite scaffolds without BMP2 fell into group D. The surface morphology and pore structure of the scaffolds were detected by scanning electron microscopy. The porosity of the scaffolds was measured by mercury intrusion porosimeter. The stress-strain curve was obtained by using the universal material testing machine to compress the scaffolds, with which their compressive strength and Young′s modulus were analyzed. Immortalized mouse embryonic fibroblasts (iMEF) were inoculated on the composite scaffolds of group A, B, C and D. At 4 and 8 days after cell inoculation, the proportion of alive and dead cells in each group was detected by cell survival/death staining; the cell counting kit-8 (CCK-8) was used to detect cell proliferation activity in each group; the positive staining cells were detected in each group by alkaline phosphatase (ALP) staining; the ALP activity was observed in each group with ALP activity detection. A total of 15 female SD rats were selected to establish osteogenesis models with ectopic muscle bag. The composite scaffolds implanted with different SF/BCNR mass ratios and the inactive composite scaffolds without BMP2 fell into group A′ (2∶1), B′ (4∶1), C′ (6∶1) and D′ respectively, and a sham operation group was set at the same time, with 3 rats in each groups. In the sham operation group, the muscle bag and skin were sutured without scaffold implantation after the incision of skin, the blunt separation of the quadriceps muscle, and the formation of muscle bag in the muscle. In the other four groups, the corresponding scaffolds were implanted in the muscle bag and the muscle bag and skin were sutured. X-ray examination was performed at 2 and 4 weeks after operation to observe the osteogenesis in each group. At 4 weeks after operation, the implanted scaffolds and tissue complexes were collected by pathological tissue sectioning, HE staining and Masson staining, and for observing the osteogenesis by in each group. Immunohistochemical staining was also performed on the tissue sections to observe the expression of osteogenic markers type I collagen (COL1) and osteopontin (OPN) in each group.Results:Scanning electron microscopy showed that the lamellar and micropore structures of group B were more regular and uniform than those of groups A and C. The porosity rate analysis showed that the porosity rates of groups B and C were (89.752±1.866)% and (84.257±1.013)% respectively, higher than that of group A [(81.171±1.268)%] ( P<0.05 or 0.01), with the porosity rate of group C lower than that of group B ( P<0.01). The mechanical property test showed that the compressive strengths of groups B and C were (0.373±0.009)MPa and (0.403±0.017)MPa respectively, higher than that of group A [(0.044±0.003)MPa] ( P<0.01), and the Young′s moduli of groups B and C were (7.413±0.094)MPa and (9.515±0.615)MPa respectively, higher than that of group A [(1.881±0.036)MPa] ( P<0.01), with the compressive strength and Young′s modulus of group C higher than those of group B ( P<0.05 or 0.01). The cell survival/death staining showed that the number of dead cells of group B was significantly smaller than that of groups A, C and D at 4 days after cell inoculation, and that group B had the most living cells and the fewest dead cells at 8 days after cell inoculation. The results of CCK-8 experiment showed that at 4 days after cell inoculation, the cell proliferation activity of groups A and B was 0.474±0.009 and 0.545±0.018 respectively, higher than 0.394±0.016 of group D ( P<0.01); the cell proliferation activity of group C was 0.419±0.005, with no significant difference from that of group D ( P>0.05), while the cell proliferation activity of groups A and C were both lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell proliferation activity of group B was 1.290±0.021, higher than 1.047±0.011 of group D ( P<0.01); the cell proliferation activity of group C was 0.794±0.032, lower than that of group D ( P<0.01); the cell proliferation activity of group A was 1.086±0.020, with no significant difference from that of group D ( P>0.05); the cell proliferation activity of groups A and C was lower than that of group B ( P<0.01). At 4 and 8 days after cell inoculation, ALP staining showed that more positive cells were found in groups A, B and C when compared with group D, and more positive cells were found in group B than in groups A and C. At 4 days after cell inoculation, the ALP activity detection showed that the ALP activity of groups A, B and C was 1.399±0.071, 1.934±0.011 and 1.565±0.034 respectively, higher than 0.082±0.003 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell activity of groups A, B and C was 2.602±0.055, 3.216±0.092 and 2.145±0.170 respectively, higher than 0.101±0.001 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). X-ray examination results showed that at 2 weeks after operation, no obvious osteogenesis was observed in the sham operation group, group D′, A′ and C′, while it was observed in group B′. At 4 weeks after operation, obvious osteogenesis was observed in group A′, B′ and C′, with significantly more osteogenesis in group B′ than in the other two groups, while there was no obvious osteogenesis in the sham operation group and group D′. At 4 weeks after operation, the HE staining and Masson staining showed that a large number of uniformly distributed new bone tissue was formed in group B′, while only a small amount of new bone tissue was found locally in groups A′ and C′, and only part of new tissue was found to grow in group D′ with no obvious new bone tissue observed. The maturity of new bone tissue formed in group B′ was higher than that in group A′ and C′. Immunohistochemical staining showed more COL1 and OPN positive staining in group B′ when compared with groups A′ and C′. The expression intensity analysis of COL1 and OPN showed that in groups A′, B′ and C′, the expression intensity of COL1 was 2.822±0.384, 22.810±2.435 and 12.480±0.912 respectively and the expression intensity of OPN was 1.545±0.081, 5.374±0.121 and 2.246±0.116 respectively, with higher expression intensity of COL1 and OPN in groups B′ and C′ than that in group A′ ( P<0.01) and lower expression intensity of COL1 and OPN in group C′ than that in B′ group ( P<0.01). Conclusions:The composite scaffold for bone regeneration is successfully fabricated with SF, BCNR and HAp. The composite scaffold with a mass ratio of SF to BCNR of 4∶1 has uniform pore structure, high porosity, good mechanical properties and biocompatibility, excellent pro-osteogenic properties in vitro, as well as excellent osteo-inductivity and osteo-conductivity.

Objective To explore the effect of mitral valve morphology on short-term and long-term outcomes in elderly patients with rheumatic mitral stenosis(MS)undergoing percutaneous balloon mitral valvuloplasty(PBMV).Methods In the prospective study,elderly patients with rheumatic mitral stenosis undergoing PBMV between February 1996 and June 2007 were followed up for 10 years.One hundred and twenty-four patients with full follow-up data were included in the study.According to echocardiography Wilkins score,83 cases of patients (Wilkins score ≤ 8)were selected as Wilkins score ≤ 8 group,and 41 cases were selected as Wilkins score＞ 8 group.The pressure gradient in mitral valve(MV△P),mitral valve area(MVA),left atrial diameter(LAD),left ventricular end-systolic diameter(LVESd),left ventricular end-diastolic diameter(LVEDd),pulmonary artery systolic blood pressure(sPAP),ejection fraction(EF)and mitral regurgitation were measured before and after the operation.Results In both Wilkins score ≤ 8 group and Wilkins score＞ 8 groups,MVA and EF were increased immediately after PBMV operation versus before PBMV operation,and MV△P,LAD,LVEDd,LVEDs and PAPs were decreased immediately after PBMV operation versus before PBMV operation(all P ＜0.05).Severe mitral regurgitation was not found in both two groups.The clinical effects of the Wilkins score≤8 group were stable after 10 years,which had no significant difference in the indexes compared with those in the Wilkins score≤ 8 group immediately after PBMV(P＞0.05).MVA and EF in the Wilkins score＞8 group were decreased,and MV△P,LAD,LVEDd,LVEDs and PAPS were increased after 10 years as compared with those immediately after PBMV(P＜0.05).The incidence of NYHA functional class Ⅲ or Ⅳ was lower in the Wilkins score ≤8 group than in the Wilkins score＞8 group(26.5％ or 22/83 vs.46.3％ or 19/41,x2 =4.879,P=0.027).And the incidence of mitral restenosis was lower in the ≤8 group than in the Wilkins score＞8 group(34.9％ or 29/83 vs.61.0％ or 25/41,x2 =7.567,P=0.006).There was no significant difference in the incidence of moderate or severe mitral regurgitation between the two groups(10.8％ or 9/83 vs.12.3％ or 5/41,x2=1.278,P=0.258).Conclusions The short-term and long-term outcomes are good in elderly individuals with rheumatic mitral stenosis undergoing PBMV operation,and the curative effect of PBMV operation is better in patients with Wilkins score ≤8 than in patients with Wilkins score ＞8.

Objective: To analyze on the identification cases of pneumoconiosis in coal enterprises in Occupational disease identification institution from 2010 to 2017. Discussion on the characteristics of pneumoconiosis identification in Coal enterprises, analyze the existing problems and put forward the countermeasures. Methods: The data of 235 pneumoconiosis cases were analyzed by the descriptive epidemiological method. Results: A total of 235 cases during this period, the mean age of onset was (51.08 ±7.17) years. The mean service length was (20.65±7.96) years. 131 cases were coal miners, accounting for 55.74%, and 132 cases were exposed to coal dust, accounting for 56.17%. The number of Identification cases was the lowest in 2011 (13 cases) , and gradually increased in the following years, with the highest number of Identification cases in 2016 (47 cases) . 96 cases came from western Chongqing, accounting for 41.20%, and 88 cases came from northeastern Chongqing, accounting for 37.77%. Pneumoconiosis stage one have accounted to 58.29%. The results of 74 cases were not consistent with those of diagnosis, and the difference rate was 31.76%. The difference rate of observation object identification results was 60.53%, and the difference rate of nonpneumoconiosisin identification results was 40.00%. Conclusion The main types of work are coal miners, and the dust exposed to them is coal dust. The regional distribution is mainly in the western part of Chongqing and the northeast part of Chongqing. The largest difference rate Pneumoconiosis Identification is observation object and nonpneumoconiosisin.

ObjectiveTo improve the correction rate of clinical, understand transpedicular vertebral intervertebral spinal shortening osteotomy for treatment of clinical efficacy of kyphosis. Methods40 patients with kyphosis,were selected as research objects. beffore and after the kyphosis correction surgery, pain improvement, efficacy and complications were retrospectively studied. ResultsBefore and after surgical correction of spinal kyphosis angle control study showed significant differences. Before and after surgical correction of grading oral pain control study showed significant differences.40 patients,the effects of surgical correction achieved grade Ⅰ ,35 cases(87.5％ ) ,grade Ⅱ in 5 cases ( 12.5％ ), grade Ⅲ and Ⅳ 0. ConclusionIntervertebral vertebral pedicle shortening osteotomy surgery could effectively correct spinal kyphosis, relieve pain and discomfort of patients, and safe, and it was worth to promote in the clinical use.

Objective To explore the relationship of serum level of Cystatin C and suPAR with tumor infiltration, metastasis, and treatment of patients with malignant tumor. Methods: The serum levels of Cystatin C was detected by particle enhanced nephelometic immunoassay (PENIA) by 7600-010 full-automatic biochemical analyzer made in Japan. The level of suPAR was detected by ELISA. The serum levels of Cystatin C and suPARof 82 normal adults and 172 patients with malignant tumor were measured and compared. Results: The serum level of Cystatin C and suPAR in patients with malignant tumor was significantly increased compared with that of normal adults (P＜0.01 and P＜0.01). The level of Cystatin C and suPAR in terminally ill patients or patients with metastasis was significantly higher than that in the control group. The levels of the two indices in postoperative patients were lower than those in preoperative patients. No significant difference was found in the levels of the two indicies before chemotherapy or radiotherapy and after therapy. Conclusion: The serum levels of Cystatin C and suPARin patients with malignant tumor are correlated with tumor invasion, metastasis and surgical intervention. Detection of Cystatin C and suPAR levels in patients with malignant tumor is valuable for disease monitoring and treatment evaluation.