Objective To investigate the mechanism of iron death induced by TRPC6/NF-κB in glomerular podiocytes mediated by high homocysteine(Hcy).Methods Mouse glomerulopocytes were cultured in vitro and divided into Control group(0 μmol/L Hcy)and Hcy group(80 μmol/L Hcy).After 48h of intervention,Western blot was used to detect the expression levels of iron death related proteins GPX4 and SLC7A11 and TRPC6 and NF-κ B.Real-time quantitative fluorescence PCR(qRT-PCR)and immunofluorescence were used to detect the expression of TRPC6.The level of podocyte apoptosis was detected by flow cytometry.Malondialdehyde(MDA)assay kit was used to determine intracellular MDA levels.After transfection of TRPC6 interference fragment and TRPC6 negative control(NC),qRT-PCR was divided into Control,si-NC and si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3).Western Blot was divided into Control,Hcy,si-NC+Hcy,si-TRPC6+Hcy.The expression of TRPC6 mRNA was detected by qRT-PCR.The expression levels of GPX4,SLC7A11,NF-κB and TRPC6 were detected by Western Blot.The level of podocyte apoptosis after interference was detected by flow cytometry.Results(1)Compared with Control group,the expression levels of iron death related proteins GPX4 and SLC7A11 in Hcy group were decreased,and the apoptosis rate was increased(P<0.05).(2)Compared with Control group,TRPC6 protein,mRNA levels and immunofluorescence expression were increased in Hcy group.The level of MDA and the expression of NF-κB signaling pathway protein increased in Hcy group,and the comparison between the two groups had statistical significance(P<0.05).(3)Compared with the si-NC group,the mRNA expression level of TRPC6 in si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3)group was decreased,and the interference effect of Si-TRPC6-3 was the best(P<0.05).After transfecting TRPC6 NC and TRPC6 interference fragment and administering Hcy,there was no difference in GPX4,SLC7A11,NF-κB and TRPC6 expression in si-NC+Hcy group compared with Hcy group.Compared with the si-NC+Hcy group,the si-TRPC6+Hcy group had higher expression of iron death related proteins,GPX4 and SLC7A11,lower expression of NF-κB and TRPC6,and decreased apoptosis rate(P<0.05).Conclusion This study confirmed that TRPC6/NF-κB can regulate iron death of renal podocytes under the induc-tion of Hcy,which is one of the mechanisms leading to kidney injury.

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

OBJECTIVE: To explore the genetic basis for a child with mental retardation. METHODS: Whole exome sequencing was carried out for the child. Candidate variant was screened based on his clinical features and verified by Sanger sequencing. RESULTS: The child was found to harbor a c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant in the SYNGAP1 gene. Bioinformatic analysis suggested it to be pathogenic. The same variant was not detected in either parent. CONCLUSION The c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant of the SYNGAP1 gene probably underlay the mental retardation in this child. Above finding has expanded the spectrum of SYNGAP1 gene variants and provided a basis for the diagnosis and treatment for this child.
Child ; Humans ; Intellectual Disability/genetics* ; Frameshift Mutation ; High-Throughput Nucleotide Sequencing ; Computational Biology ; Heterozygote ; Mutation ; ras GTPase-Activating Proteins/genetics*

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles

Purpose: Lymphoblastic lymphoma (LBL) is an invasive neoplasm of precursor T-cell or B-cell lineage.A broadly accepted standard treatment for adult LBL has not yet been defined. Materials and Methods: To address this issue, we compared two chemotherapy regimens: a modified non-Hodgkinlymphoma Berlin–Frankfurt–Mu!nster-95 (NHL-BFM-95) regimen and HyperCVAD/MA. Thisretrospective study consecutively enrolled 207 adult LBL patients at two hospitals from2000 to 2018. Univariate and multivariate analysis were used to assess prognostic factors. Results: In the present study, most clinical characteristics were similar between the two treatmentgroups except for age and lactate dehydrogenase (LDH) level. Patients treated with modifiedNHL-BFM-95 regimen tended to be younger and with elevated LDH level. The modified NHLBFM-95 regimen produced better treatment outcomes than those with HyperCVAD/MA inpatients with T-LBL or patients < 40 years. Treatment with HyperCVAD/MA, high EasternCooperative Oncology Group scores, and bone marrow involvement were independent riskfactors in T-LBL. No patients interrupted treatment for severe adverse events. Conclusion The results suggested that the modified regimen is well-tolerated and can produce the promisingoutcomes in patients with T-LBL or patients < 40 years.

Objective To investigate the related factors and preventive measures of delayed gastric emptying after operation for esophageal and cardiac carcinoma.Methods A total of 45 patients with delayed gastric emptying after operation for esophageal and cardiac carcinoma were selected as observation group,and 45 patients without delayed gastric emptying after operation for esophageal and cardiac carcinoma were selected as control group.Differences in the relevant factors were compared between the two groups.Results Single factor analysis showed that older age,high body mass index,short time education,malnutrition,poor mental state,rural residence,surgical incision,blood loss,long operation time,postoperative analgesia pump application,and the large amount of fluid volume were related risks of delayed gastric emptying (P ＜ 0.05).The Logistic regression analysis showed that older age (OR =4.15,95 ％ CI:1.89 ～ 26.30),bad psychological reaction (OR =3.96,95％ CI:1.38 ～ 25.38),long operation time (OR =3.40,95％ CI:1.11 ～ 20.28) and malnutrition (OR =3.02,95％ CI:1.09 ～ 19.35) were independent factors of delayed gastric emptying.Conclusion Delayed gastric emptying is one of the common complications after operation for esophageal and cardiac carcinoma,and the influencing factors are complex.

Objective To investigate the related factors and preventive measures of delayed gastric emptying after operation for esophageal and cardiac carcinoma.Methods A total of 45 patients with delayed gastric emptying after operation for esophageal and cardiac carcinoma were selected as observation group,and 45 patients without delayed gastric emptying after operation for esophageal and cardiac carcinoma were selected as control group.Differences in the relevant factors were compared between the two groups.Results Single factor analysis showed that older age,high body mass index,short time education,malnutrition,poor mental state,rural residence,surgical incision,blood loss,long operation time,postoperative analgesia pump application,and the large amount of fluid volume were related risks of delayed gastric emptying (P ＜ 0.05).The Logistic regression analysis showed that older age (OR =4.15,95 ％ CI:1.89 ～ 26.30),bad psychological reaction (OR =3.96,95％ CI:1.38 ～ 25.38),long operation time (OR =3.40,95％ CI:1.11 ～ 20.28) and malnutrition (OR =3.02,95％ CI:1.09 ～ 19.35) were independent factors of delayed gastric emptying.Conclusion Delayed gastric emptying is one of the common complications after operation for esophageal and cardiac carcinoma,and the influencing factors are complex.

Objective:To compare the alveolar cortical bone density and thickness of jaw bones between teenagers (12-18 years of age) and adults(19-48 years of age).Methods:Spiral computed tomographic images of 60 cases were obtained from the subjects with the ages of 12 to 48 years(27 Males and 33 females,35 teenagers and 25 adults).Buccal cortical bone thickness and density in Hounsfield units were measured at 12 interradicular sites and to a depth of 14 mm.Results:The alveolar cortical bone thicknesses and densities of the jaw bones significantly increased from the crest to base of alveolar crest.The average cortical bone thicknesses rangedfrom 1.0 to 1.5 mm in the anterior part of the jaw bones,1.1 to 1.8 mm in maxillary posterior area and 1.5 to 2.8 mm in the mandible posterior areas.The cortical bone thickness and density were greater in the mandible than in the maxilla(P ＜ 0.05).The thickness values did not show difference between males and females,between adolescents and adults.Higher values of bone density were found in the adults than in the teenagers(P ＜0.05).The highest bone density in the mandible posterior area of adults was observed,and the lowest bone density in the maxillary posterior area of adolescents.Conclusion:Alveolar cortical bone density of adolescents is lower than that of adults,especially in the maxilla posterior region.

BACKGROUND:The self-renew and regeneration capacity of the injured spinal cord is thought to be limited. Accordingly, cel transplantation is one potential strategy for promoting functional recovery after spinal cord injury. OBJECTIVE:To explore the effects ofPTEN silencing on the biological properties of bone marrow mesenchymal stem cels, hoping to offer better seed cels for tissue engineering. METHODS:Bone marrow mesenchymal stem cels were transfected with specific siRNA-silencedPTEN gene using the liposome method, and then RT-PCR was used to detect the mRNA expression ofPTEN. Variation of biological properties ofPTEN-transfected cels were detected by the way of MTT assay, cel cycle analysis, and Transwel assay. RESULTS AND CONCLUSION:PTEN is expressed highly in bone marrow mesenchymal stem cels, which is successfuly interfered by siRNA.PTEN-silenced cels have stronger survival, proliferation and migration abilities, which become a kind of better seed cels for tissue engineering.

Aim To study whether the mechanisms in-volved in resveratrol′s protective effects on vascular en-dothelial injury induced by high-calorie and high-chol-estrol diet are concerned with ERS and the change of eNOS expression. Methods Twenty-four male C57BL/6 mice were randomly divided into standard control diet (SCD),high-calorie and high-cholestrol diet(HCD)and HCD group treated with resveratrol (HCD +RES,400 mg·kg -1 ·d -1 ,1 2 weeks).Then the thoracic aorta was separated,embedded and sliced to analyze the pathological changes by HE and resor-cinol staining.The protein distribution of eNOS was measured with immunohistochemical analysis.The up-stream and downstream genes of ERS in thoracic aorta were detected by RT-PCR.After the pretreatment with different concentrations of resveratrol,the mouse aortic endothelial cells (MAECs)were treated with palmitic acid,then the changes of cell proliferation in each group were compared.Western blot,immunofluores-cence and immunohistochemistry were used to deter-mine the protein expressions of GRP78,CHOP and eNOS respectively.Results Mice fed with HCD showed thickening of thoracic aortic wall and disorgan-ized elastic fibers as compared with those in SCD group.The mRNA levels of ERS related genes were all increased obviously (P <0.05),while the protein expression of eNOS was decreased.Compared with HCDgroup,the thickened wall and the disorganized elasticfibers were improved significantly,the mRNA levels ofERS related genes were all decreased obviously (P <0.05)and the expression of eNOS protein was increased in HCD +RES group.Compared with NCgroup, the cell proliferation was significantly decreased,meanwhile GRP78 and CHOP was significantly increased (P <0.05)and the protein expression ofeNOS was decreased in PA group.The cell proliferation was increased significantly (P <0.05),the mRNA and protein expression of GRP78 and CHOP wasobviously decreased (P <0.05),meanwhile the protein expression of eNOS was increased in the mediumand large dose of RES pretreatment groups.Conclusion Resveratrol has obvious effects of improving endothelial damages induced by HCD and decreasing cellproliferateion of MAECs induced by PA, and themechanisms are possibly related with decreased ERSand increased level of eNOS protein.