Objective: To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods. Methods: Comprehensive analysis was performed in available mRNA microarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus(GEO) database. Gene ontology enrichment analysis, gene pathway enrichment analysis and protein interaction network analysis were performed based on significantly correlated genes. The expression level of genes was validated in the cancer genome atlas(TCGA) dataset. Survival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publications genomics of drug sensitivity in cancer(GDSC) database in CellMiner cross database(CellMiner CDB), Pearson correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maximal inhibitory concentration(IC50) of anticancer drugs. Results : There were a total of 77 genes which had a different expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues. The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule, extracellular exosome, cell cycle and signaling by nuclear receptors. Protein-protein interactions(PPI) network screened 6 most connected genes as molecular complex(MCODE). Among the MCODE, overexpressed ubiquitin conjugating enzyme E2 T(UBE2T), kinesin family member 20A(KIF20A), PCNA clamp associated factor(KIAA0101), pituitary tumor-transforming gene 1(PTTG1) and NIMA related kinase 2(NEK2) were associated with poor outcomes. Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients. Drug sensitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensitivity to multiple anticancer drugs, including paclitaxel and docetaxel. RT-PCR validation showed that PTTG1 andUBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR. Conclusion PTTG1 andUBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.

Objective:To explore the clinical effect on the treatment of radiation induced deep ulcers in the inguinal region with ipsilateral anterolateral thigh chimeric perforator flap.Methods:From March 2020 to March 2024, retrospective analysis of 8 patients with radiation induced deep ulcers in the inguinal region were treated with ipsilateral anterolateral thigh chimeric perforator flap in the Medical Centre of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University. All ulcers induced by radiation were caused by postoperative radiotherapy in the inguinal region, of which 4 were of vulvar or penile cancer, 2 of urinary tract tumour, 1 of inguinal protuberant dermatofibrosarcoma and 1 of myofibroblastic sarcoma in lower abdominal wall. The course of the radiation induced ulcer was 0.5-11.0 years, with an average of 2.9 years. The sizes of the ulcerative wound were 2.5 cm × 3.0 cm - 5.5 cm × 7.5 cm. Preoperative biopsies of the tissues around wound and pelvic CT scans were performed to preliminarily exclude a tumour recurrence or an ulcerative malignancy, as well as to confirm the depth of radiation ulcer. The wound size after debridement was 4.5 cm × 6.0 cm-13.5 cm × 19.0 cm, with a depth of 2.0-4.0 cm. An ipsilateral anterolateral thigh chimeric perforator flap was transferred to reconstruct the wound, after the wound edges were cleared from tumour through intraoperative frozen section examinations. The flaps were 5.5 cm × 7.0 cm - 14.0 cm × 20.0 cm in size, with the volumes of muscle flap at 7.0 cm × 4.0 cm × 3.0 cm - 14.0 cm × 7.0 cm × 3.0 cm. After having the deep defect at the base of wound filled with a muscle flap, the wound surface was covered by the flap. Four patients had direct suture of the donor sites and 4 received a thick skin graft of head or contralateral thigh grafting. Survival of the anterolateral thigh chimeric perforator flaps and the healing of donor sites were observed after surgery through scheduled postoperative follow-up by the visits of outpatient clinic and distant interviews via telephone, WeChat or the internet hospital.Results:One of the ipsilateral anterolateral thigh chimeric perforator flaps had venous occlusion within 24 hours after surgery. Emergency surgical exploration revealed that it was caused by a haematoma compression due to haemorrhage in the muscle flap. Further debridement, haemostasis and suture were performed, then the wound healed. The rest of 7 flaps all survived. All donor sites healed primarily. The postoperative follow-up lasted for 5-17 months with all of the 8 patients, at 8.4 months in average. Both the donor and recipient sites healed well without recurrence of radiation ulcer in the affected sites. The appearance and texture of the flaps were good, and there was no obvious functional impairment at the donor sites.Conclusion:The treatment of radiation induced deep ulcer in the inguinal region with an ipsilateral anterolateral thigh chimeric perforator flap has shown good results, without recurrence of ulcer after surgery. The appearance and texture of the affected sites are good, and there is no secondary functional impairment at the donor site.

Objective To establish a cellular model of Parkinson disease by treating retinoic acid(RA)-differentiated SH-SY5Y cells with α-synuclein preformed fibrils(α-Syn PFF).Methods SH-SY5Y cells were divided into undifferentiated and RA-differentiated groups.The expression levels of tyrosine hydroxylase(TH),dopamine transporter(DAT),lymphocyte activation gene 3(LAG3),and Nestin proteins in the cells were detected using Western blotting,whereas those of microtubule-associated protein 2(MAP2)and neu-ronal nuclei(NeuN)were detected using immunofluorescence staining.Furthermore,RA-treated SH-SY5Y cells were divided into control and α-Syn PFF groups,and their levels of chromatin condensation were detected using Hoechst 33342 staining.Nitric oxide(NO)levels were measured using a NO assay kit.Additionally,the protein levels of TH,poly(ADP-ribose)(PAR),and poly(ADP-ribose)poly-merase(PARP)in these cells were detected using Western blotting,whereas their expression levels of phosphorylated α-Syn(pS129-α-Syn)and phosphorylated histone H2AX(γH2AX)were detected using immunofluorescence staining.Results Treatment with RA resulted in a reduction in cell body size and the elongation of protrusions in SH-SY5Y cells.The results of Western blotting showed that RA treatment could increase the TH,DAT,and LAG3 levels and decrease the Nestin level in SH-SY5Y cells(P＜0.05).α-Syn PFF treat-ment decreased the TH protein level and increased the PAR,PARP-l,and cleaved PARP-1 levels in differentiated SH-SY5Y cells(P＜0.05).According to the immunofluorescence results,RA treatment increased the expression levels of MAP2 and NeuN in SH-SY5Y cells(P＜0.001).The α-Syn PFF treatment increased the expression levels of γH2AX and pS129-α-Syn in RA-differentiated SH-SY5Y cells(P＜0.01).The Hoechst 33342 staining results showed that α-Syn PFF treatment led to chromatin condensation in the differentiated SH-SY5Y cells(P＜0.001)and increased the NO levels(P＜0.01).Conclusion A cellular model of Parkinson disease can be established by treating RA-differentiated SH-SY5Y cells with α-Syn PFF.

Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.

Objective To establish a cellular model of Parkinson disease by treating retinoic acid(RA)-differentiated SH-SY5Y cells with α-synuclein preformed fibrils(α-Syn PFF).Methods SH-SY5Y cells were divided into undifferentiated and RA-differentiated groups.The expression levels of tyrosine hydroxylase(TH),dopamine transporter(DAT),lymphocyte activation gene 3(LAG3),and Nestin proteins in the cells were detected using Western blotting,whereas those of microtubule-associated protein 2(MAP2)and neu-ronal nuclei(NeuN)were detected using immunofluorescence staining.Furthermore,RA-treated SH-SY5Y cells were divided into control and α-Syn PFF groups,and their levels of chromatin condensation were detected using Hoechst 33342 staining.Nitric oxide(NO)levels were measured using a NO assay kit.Additionally,the protein levels of TH,poly(ADP-ribose)(PAR),and poly(ADP-ribose)poly-merase(PARP)in these cells were detected using Western blotting,whereas their expression levels of phosphorylated α-Syn(pS129-α-Syn)and phosphorylated histone H2AX(γH2AX)were detected using immunofluorescence staining.Results Treatment with RA resulted in a reduction in cell body size and the elongation of protrusions in SH-SY5Y cells.The results of Western blotting showed that RA treatment could increase the TH,DAT,and LAG3 levels and decrease the Nestin level in SH-SY5Y cells(P＜0.05).α-Syn PFF treat-ment decreased the TH protein level and increased the PAR,PARP-l,and cleaved PARP-1 levels in differentiated SH-SY5Y cells(P＜0.05).According to the immunofluorescence results,RA treatment increased the expression levels of MAP2 and NeuN in SH-SY5Y cells(P＜0.001).The α-Syn PFF treatment increased the expression levels of γH2AX and pS129-α-Syn in RA-differentiated SH-SY5Y cells(P＜0.01).The Hoechst 33342 staining results showed that α-Syn PFF treatment led to chromatin condensation in the differentiated SH-SY5Y cells(P＜0.001)and increased the NO levels(P＜0.01).Conclusion A cellular model of Parkinson disease can be established by treating RA-differentiated SH-SY5Y cells with α-Syn PFF.

Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.

Objective:To explore the clinical effect on the treatment of radiation induced deep ulcers in the inguinal region with ipsilateral anterolateral thigh chimeric perforator flap.Methods:From March 2020 to March 2024, retrospective analysis of 8 patients with radiation induced deep ulcers in the inguinal region were treated with ipsilateral anterolateral thigh chimeric perforator flap in the Medical Centre of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University. All ulcers induced by radiation were caused by postoperative radiotherapy in the inguinal region, of which 4 were of vulvar or penile cancer, 2 of urinary tract tumour, 1 of inguinal protuberant dermatofibrosarcoma and 1 of myofibroblastic sarcoma in lower abdominal wall. The course of the radiation induced ulcer was 0.5-11.0 years, with an average of 2.9 years. The sizes of the ulcerative wound were 2.5 cm × 3.0 cm - 5.5 cm × 7.5 cm. Preoperative biopsies of the tissues around wound and pelvic CT scans were performed to preliminarily exclude a tumour recurrence or an ulcerative malignancy, as well as to confirm the depth of radiation ulcer. The wound size after debridement was 4.5 cm × 6.0 cm-13.5 cm × 19.0 cm, with a depth of 2.0-4.0 cm. An ipsilateral anterolateral thigh chimeric perforator flap was transferred to reconstruct the wound, after the wound edges were cleared from tumour through intraoperative frozen section examinations. The flaps were 5.5 cm × 7.0 cm - 14.0 cm × 20.0 cm in size, with the volumes of muscle flap at 7.0 cm × 4.0 cm × 3.0 cm - 14.0 cm × 7.0 cm × 3.0 cm. After having the deep defect at the base of wound filled with a muscle flap, the wound surface was covered by the flap. Four patients had direct suture of the donor sites and 4 received a thick skin graft of head or contralateral thigh grafting. Survival of the anterolateral thigh chimeric perforator flaps and the healing of donor sites were observed after surgery through scheduled postoperative follow-up by the visits of outpatient clinic and distant interviews via telephone, WeChat or the internet hospital.Results:One of the ipsilateral anterolateral thigh chimeric perforator flaps had venous occlusion within 24 hours after surgery. Emergency surgical exploration revealed that it was caused by a haematoma compression due to haemorrhage in the muscle flap. Further debridement, haemostasis and suture were performed, then the wound healed. The rest of 7 flaps all survived. All donor sites healed primarily. The postoperative follow-up lasted for 5-17 months with all of the 8 patients, at 8.4 months in average. Both the donor and recipient sites healed well without recurrence of radiation ulcer in the affected sites. The appearance and texture of the flaps were good, and there was no obvious functional impairment at the donor sites.Conclusion:The treatment of radiation induced deep ulcer in the inguinal region with an ipsilateral anterolateral thigh chimeric perforator flap has shown good results, without recurrence of ulcer after surgery. The appearance and texture of the affected sites are good, and there is no secondary functional impairment at the donor site.

Objective: To investigate the effects of long-term hyperglycemia on renal pathology of type 1 diabetic mellitus(T1DM) cynomolgus monkeys by establishing streptozotocin(STZ)-induced T1DM. Methods: Eight 4-year-old male cynomolgus monkeys were randomly divided into control and model groups. Four cynomolgus monkeys were used in the control group, and four cynomolgus monkeys were injected with streptozotocin to create a T1DM model. Hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining were used to observe renal pathological changes.The histological characteristics and changes were observed under transmission electron microscope. Morphometric measurements were used to analyze the glomerular area, the thickness of the glomerular basement membrane, the proportion of glomerular podocyte foot processes and the average area of foot processes. Results: In comparison to the control group, the model group showed pathological changes in the kidneys, including increased glomerular area(P<0.01), thickened basement membrane, capillary loop compression, disordered arrangement of endothelial cell fenestrations, proliferation of mesangial cells, mesangial expansion, accumulation of mesangial matrix glycoproteins, a decrease in the number of foot processes(P<0.001), a decrease in the average size of the foot processes(P<0.05), widened podocyte slit diaphragm, and an increase in the number of fused foot processes(P<0.001). Conclusion Cynomolgus monkeys with T1DM suffer from renal pathological changes due to long-term hyperglycemia.

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

Objective:To explore the effect of constructing WeChat platform and introducing PPT (PowerPoint) optimized by Media studio pro editing technology in the teaching of radiation therapeutics.Methods:Sixty undergraduates of medical imaging technology in Fujian Medical University were randomly divided into experimental group and control group in average. The experimental group set up a WeChat group and acquired the optimized PPT before class; control group received classroom teaching and clinical practice according to the traditional teaching mode. Twenty-four items of MCTQ (Maastricht clinical teaching questionnaire) were selected and translated. A total of 30 teachers majoring in tissue radiation oncology and medical imaging were randomly divided into two groups. The questionnaire was used to evaluate the two teaching models. To examine the academic performance of the two groups of students. SPSS 23.0 software was used for independent sample t-test. Results:By comparing the scores of MCTQ questionnaire between the two groups, it was concluded that the teaching mode of the experimental group had significant advantages in 11 aspects, such as clinical practice, obtaining more learning opportunities and so on ( P < 0.05). The scores of practice [(84.67±7.29) vs. (80.03±8.97)] and final evaluation [(81.53±8.78) vs. (76.77±9.49)] of the students in the experimental group were better than those in the control group ( P < 0.05). Conclusion:The application of optimized PPT by Media studio pro editing technology based on WeChat platform is worth popularizing in the teaching of radiation therapeutics.