PTEN-induced putative kinase 1 (PINK1), a Parkinson's disease (PD)-related protein, has two isoforms, the mitochondria-localized full-length isoform PINK1FL and the cytoplasm-localized short isoform PINK1-cyto. Studies have suggested that PINK1FL can selectively accumulate at the surface of damaged mitochondria and cooperate with another Parkinson's Disease-related protein PARKIN to trigger the degradation of MIRO1, a mitochondria trafficking regulator. The functions of PINK1-cyto are, however, not yet clear. To investigate the functions of PINK1-cyto, we expressed different proteins in cultured HEK293 cells by transfecting it with different plasmids, and detected the protein levels by Western blot after expressing for 24 h. We found that in cultured HEK293 cells, PINK1-cyto could also cooperate with PARKIN degrade MIRO1 in the presence of CK23, and the regulatory subunit of Casein Kinase II. Interestingly, this function of CK2P was not dependent on CK2alpha, the catalytic subunit of Casein Kinase II. We also found that CK2P could promote the direct interaction between PINK1-cyto and MIRO1 by immunocoprecipitation analysis. This result suggested that in addition to CK2alpha, CK2beta could also form a kinase complex.
Casein Kinase II ; metabolism ; HEK293 Cells ; Humans ; Mitochondrial Proteins ; metabolism ; Parkinson Disease ; Protein Kinases ; metabolism ; Protein Transport ; Ubiquitin-Protein Ligases ; metabolism ; rho GTP-Binding Proteins ; metabolism

Objective To discuss the impact of a immunosuppressive protocol using tacrolimus combined with mycophenolate without steroid on glycometabolism after liver tansplantation (LT).Methods 295 adult liver transplant recipients were under investigation and divided into two groups,to receive immunosuppression therapy using tacrolimus and mycophenolate with (n =142) or without steroid (n =153).The fasting blood-glucose level,rate of hyperglycemia,infection and metabolic complications were followed up at 1st,2nd,4th,8th,12th,16th,20th and 24th week after LT.Results There were no significant differences between two groups in gender,age.body weight and FBG level before LT.In both groups,the FBG levels were significantly elevated immediately and reached the peak at 1st week after LT,then gradually decreased over time post-LT.The FBG level and rate of hypcrglycemia were significantly lower in steroid-free group than in steroid group in each observation time point with the differences being significant (P＜0.05) at 4th week post-LT.The overall rate of hyperglycemia was 52.9％ in steroid free group and 76.8％ in steroid group with the difference being significant between the two groups (P＜0.05) and a risk ratio of 2.94 (steroid-free group versus steroid group).The rate of acute rejection was slightly higher in steroid-free group (8.50 ％ ) than in steroid group (7.75％ ) (P ＞ 0.05 ).Also the incidence of intention badness,infection and hypercholesterinemia was significantly lower in steroid group than in steroid-free group.Conclusion The immunosuppressive protocol without steroids is safe and effective of reducing the risk of hyperglycemia and metabolic complications after LT.

OBJECTIVE:To study the effects of paclitaxel combined with cisplatin on the proliferation,migration and invasion of thyroid cancer cells SW579 and its mechanism. METHODS:Cells were divided into blank control group,paclitaxel group (3μmol/L),cisplatin group(30 μmol/L),drug combination group(paclitaxel 3 μmol/L+cisplatin 30 μmol/L). 48 h after culture,the relative cell activity was measured by MTT assay. Cell cycle was detected by flow cytometry. Migration and invasion of cell was tested by Transwell assay. The expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN),protein kinase B(AKT),Cyclin D1,p27,matrix metalloproteinase(MMP)-2 and MMP-9 were detected by Western blot. RESULTS:Compared with blank control group,relative cell activity of all treatment groups were decreased;paclitaxel or plus cisplatin also made cell cy-cle arrest in G1 phase,and migration and invasion ability of cell were decreased;the expression of PTEN and p27 remarkably in-creased,while the expression of Cyclin D1,MMP-2,MMP-9 and phosphorylation of AKT were obviously reduced,with statisti-cal significance (P<0.05). Compared with single drug group,the effect of drug combination group strengthened,with statistical significance in above indicators(P<0.05). CONCLUSIONS:The inhibition effect of paclitaxel combined with cisplatin on the pro-liferation,migration and invasion of thyroid cancer cells SW579 cell will be strengthened,by a mechanism of up-regulating the ex-pression of PTEN and p27,down-regulating the expression of Cyclin D1,MMP-2 and MMP-9,inhibiting phosphorylation of AKT.

Objective:To analyze the current situation of falls in elderly patients with infirmity, and find out the related risk factors of injuries caused by falls, so as to provide reference for avoiding or reducing the injuries caused by falls in elderly patients with infirmity during hospitalization.Methods:Using the method of data mining, this paper analyzed the data of 56 elderly patients with falls reported by a tertiary hospital in Liaoning Province from January 1, 2017 to April 30, 2020. Through the Apriori algorithm for association analysis, using chi square test for effectiveness evaluation, and then according to the relevant professional knowledge for analysis.Results:Finally obtained six strong association rules with the elderly infirmity inpatients fall injury, which were poor sleep quality, poor activity ability, taking fall prone drugs, falling state for displacement, suffering from cerebrovascular disease, self-care ability was limited.Conclusion:Association analysis can be used to mine valuable association rules of fall injury in elderly patients, and attach importance to its strong association rules, so as to provide clinical intervention basis for preventing or reducing fall injury in elderly patients.

Objective:To investigate the clinical effect of the medial perforator flap of the first plantar artery for repairing the soft tissue defect near the first metatarsophalangeal joint.Methods:From January 2016 to April 2018, 10 patients of soft tissue defect near the first metatarsophalangeal joint were treated in the Department of Orthopedics, Shandong Police General Hospital, including 6 males and 4 females, aged 22-61 years old, with an average age of 40 years. The defects of the feet were recovered by the medial perforator flap of the first plantar artery, and the flap donor defects were covered by split-thickness skin grafts.Results:All flaps and skin grafts of the patients were survived.All patients were followed up for 12-22 months postoperationly/after operation. The flaps were not swollen or ruptured, and the patients walked normally with full weight-bearing.Conclusions:The perforator artery of this flap is consistant, the harvesting of the flap is simple, and the texture of skin is similarwith surrounding tissue, there is no deficit to the flood supply of the foot after harvesting the flap. So, it is an ideal choice for repairing the defect of the soft tissue near the first metatarsophalangeal joint.

Objective:To investigate the clinical effect of the medial perforator flap of the first plantar artery for repairing the soft tissue defect near the first metatarsophalangeal joint.Methods:From January 2016 to April 2018, 10 patients of soft tissue defect near the first metatarsophalangeal joint were treated in the Department of Orthopedics, Shandong Police General Hospital, including 6 males and 4 females, aged 22-61 years old, with an average age of 40 years. The defects of the feet were recovered by the medial perforator flap of the first plantar artery, and the flap donor defects were covered by split-thickness skin grafts.Results:All flaps and skin grafts of the patients were survived.All patients were followed up for 12-22 months postoperationly/after operation. The flaps were not swollen or ruptured, and the patients walked normally with full weight-bearing.Conclusions:The perforator artery of this flap is consistant, the harvesting of the flap is simple, and the texture of skin is similarwith surrounding tissue, there is no deficit to the flood supply of the foot after harvesting the flap. So, it is an ideal choice for repairing the defect of the soft tissue near the first metatarsophalangeal joint.

Objective:To evaluate the efficacy and safety of peroral endoscopic myotomy (POEM) in achalasia of cardia (AC) patients with the long course.Methods:A total of 159 AC patients who received POEM from January 2015 to March 2022 in the First Affiliated Hospital of Soochow University were divided into the long course group (≥10 years) and the non-long course group (<10 years). The baseline information, POEM procedure and postoperative recurrence were compared and the differences between the recurrent patients and non-recurrent patients in the long course group were explored.Results:The age (57.09±14.30 years VS 42.08±15.68 years, t=5.569, P<0.001), the rate of treatment history [28.9% (13/45) VS 9.6% (11/114), χ2=9.319, P=0.020], the proportion of Henderson grade Ⅲ esophagus [17.8% (8/45) VS 6.1% (7/114), χ2=7.020, P=0.030] in the long course group were significantly higher than those in the non-long course group. The recurrence rate in the long course group was significantly higher than that in the non-long course group [33.3% (15/45) VS 14.9% (17/114), χ2=6.811, P=0.009]. In the long course group, the age (62.50 ± 16.94 years VS 53.77 ± 12.95 years, t=-2.121, P=0.040), and the rate of treatment history [53.3% (8/15) VS 16.7% (5/30), χ2=6.544, P=0.016] in the recurrent patients were higher than those in the non-recurrent patients. Conclusion:POEM is safe and effective for long-course AC patients. In patients with the long course, the aged patients with previous treatment are more likely to relapse.

Objective:To investigate the diagnostic value of lung ultrasound in hospitalized children with community-acquired pneumonia (CAP).Methods:In the cross-sectional study, a total of 422 children with CAP who were hospitalized in the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University, from February 2021 to August 2022 and completed lung ultrasound examination within 48 hours after admission were enrolled. The clinical characteristics, lung ultrasound and chest CT were collected. The patients were divided into two groups according to the signs of pneumonia indicated by chest CT, and the signs of lung ultrasound with diagnostic value were screened according to the signs of pneumonia indicated by chest CT by least absolute shrinkage and selection operator (Lasso) regression. According to severity of the disease, the children were divided into the severe group and the mild group, and the differences of lung ultrasound signs between the two groups were compared. Kruskal-Wallis test, Fisher′s exact test was selected for comparison between groups. Random forest classifier wes used to evaluate the value of lung ultrasound in the diagnosis of CAP and prediction of severe pneumonia in children. The receiver operating characteristic curve was used to evaluate the prediction effect. Use DeLong test to compare the area under the curve.Results:Among the 422 cases of CAP, there were 258 males and 164 females, and the age of onset was 2.8 (1.3, 4.3) years. The confluent B-line, consolidation and pleural effusion detected by lung ultrasound were 309 cases (73.2%), 232 cases (55.0%) and 16 cases (3.8%), respectively, and the size of consolidation was 3.0 (0, 11.0) mm. One hundred and ten children (26.1%) with CAP completed chest CT. There were 90 cases with signs of pneumonia in chest CT and 20 cases without signs of pneumonia. Lasso was used for feature selection.Lung consolidation ( OR=2.46), bilateral lung consolidation ( OR=1.16) and confluent B-line ( OR=1.34) were the main index. With random forest classifier, the accuracy of models using full variables and Lasso-selected variables were 0.79 (95% CI 0.70-0.86) and 0.79 (95% CI 0.70-0.86), the sensitivity were 0.81 and 0.81, and the specificity were 0.75 and 0.70, and the area under curve were 0.87 (95% CI 0.81-0.94, P<0.001) and 0.84 (95% CI 0.76-0.91, P<0.001), respectively. There were 97 cases in severe group and 325 cases in mild group. Compared with the mild group, the detection rate of consolidation, multiple consolidation, the size of consolidation and the size of consolidation was adjusted by body surface area (consolidation size/body surface area) in severe group were higher (66 cases (68.0%) vs. 166 cases (51.1%), 42 cases (43.3%) vs. 93 cases (28.6%), 8.0 (0, 17.0) vs. 1.0 (0, 9.0) mm, 12.5 (0, 24.6) vs. 2.1 (0, 17.6), χ2=8.59, 9.98, Z=14.40, 12.79, all P<0.05). Using lung ultrasound lung consolidation size and consolidation size/body surface area to predict the severe CAP, the optimal cut-off value were 6.7 mm and 10.2, the accuracy was 0.80 (95% CI 0.75-0.83) and 0.89 (95% CI 0.86-0.92), the sensitivity was 0.99 and 0.99, the specificity was 0.14 and 0.56, respectively, and the area under the curve was 0.66 (95% CI 0.60-0.72, P<0.001) and 0.76 (95% CI 0.70-0.83, P<0.001), respectively. The area under the curve of consolidation size/body surface area was higher than that of consolidation size ( Z=5.50, P<0.001). Conclusions:Consolidation and confluent B-line, are important index for lung ultrasound diagnosis of CAP in children. The actual consolidation size adjusted by body surface area is superior to the size of consolidation in predicting severe CAP.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.