BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Objective:To study the effects of the alternate rapid maxillary expansion and constriction(Alt-RAMEC)with maxillary protraction on different parts of upper airway by CBCT.Methods:20 Angle Class Ⅲ patients aged 9-12 years were included,and CBCT images were taken before treatment and after Alt-RAMEC with maxillary protraction,the total volume of the upper airway,the volume of each part of the nasopharynx,palatopharynx,linguopharynx and laryngopharynx,the cross-sectional area of the division in-terface,and the minimum cross-sectional area were measured after 3D reconstruction using Dolphin software,the data were analyzed using SPSS 26.0 software.Results:The total upper airway volume,nasopharyngeal volume,and palatopharyngeal volume were in-creased by the average of 1 385.39 mm3(P=0.013),546.74 mm3(P=0.011)and 768.03 mm3(P=0.035)respectively after Alt-RAMEC with maxillary protraction treatment;the area of the nasopharyngeal and palatopharyngeal division interface increased by 73.79 mm2(P=0.002),the cross-sectional diameter by 1.41 mm(P=0.037),and sagittal diameter by 1.52 mm(P=0.022)respectively;however,there was no statistically significant change in the volume,minimum cross-sectional area,partition area,and partition transverse and sagittal diameters of the linguopharynx and laryngopharynx(P＞0.05).Conclusion:Alt-RAMEC with maxil-lary protraction can significantly increase nasopharyngeal and palatopharyngeal volumes,with no significant effect on the linguopharyn-geal and laryngopharyngeal segments of the airway.

Objective:To detective the cut-off values of amino acid levels in premature infants in Sichuan.Methods:Data of newborns screening for inherited metabolic diseases (IMD) by tandem mass spectrometry in Sichuan Province from January 2018 to December 2019 were retrospectively analyzed.They were divided into premature infant group ( n=2 264, 1 312 males and 952 females) and full-term infant group ( n=53 275, 28 269 males and 25 006 females). The cut-off values of amino acids in dry blood spots were expressed as percentage ( P0.5 - P99.5), and rank sum test was used for comparison between preterm and full-term infants. Results:(1) The distribution of 11 amino acids [alanine (ALA), arginine (ARG), citrulline (CIT), glycine(GLY), leucine (LEU), methionine (MET), ornithine (ORN), phenylalanine (PHE), proline (PRO), tyrosine (TYR) and valine (VAL)] in premature infants were abnormal.(2) The cut-off values of amino acids in premature infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.34-47.04 μmol/L, CIT: 5.66-32.02 μmol/L, GLY: 181.48-909.93 μmol/L, LEU : 71.10-283.29 μmol/L, MET: 4.21-34.51 μmol/L, ORN: 40.58-293.76 μmol/L, PHE: 23.60-106.30 μmol/L, PRO: 77.76-358.24 μmol/L, TYR: 27.52-352.91 μmol/L, VAL: 53.74-228.37 μmol/L.(3) The cut-off values of amino acid in full-term infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.30-42.73 μmol/L, CIT: 5.92-30.35 μmol/L, GLY: 208.17-980.09 μmol/L, LEU: 72.91-287.49 μmol/L, MET: 4.27-33.90 μmol/L, ORN: 48.40-305.59 μmol/L, PHE: 27.63-92.27 μmol/L, PRO: 97.38-372.75 μmol/L, TYR: 40.19-276.54 μmol/L, VAL: 65.75-237.92 μmol/L.(4) Except for PHE ( Z=-0.58, P>0.05), the other indicators were significantly different between 2 groups [ALA ( Z=-15.32, P<0.05), ARG ( Z=-5.62, P<0.05), CIT ( Z=-5.86, P<0.05), GLY ( Z=-14.52, P<0.05), LEU ( Z=-5.62, P<0.05), MET ( Z=-5.22, P<0.05), ORN ( Z=-13.01, P<0.05), PRO ( Z=-22.09, P<0.05), TRY ( Z=-2.09, P<0.05), VAL ( Z=-17.82, P<0.05)]. Conclusions:The establishment of the cut-off values of amino acids in premature infants in Sichuan provides a theoretical basis for laboratory diagnosis of IMD screening, which enhances the accuracy of diagnosis and avoids excessive medical treatment.

Objective:To investigate the risk factors for abdominal infection after liver transplantation (LT).Methods:The retrospective case-control study was conducted. The clinical data of 356 patients who underwent LT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2015 to December 2018 were collected. There were 273 males and 83 females, aged from 21 to 67 years, with the median age of 46 years. Observation indications: (1) abdominal infec-tion after LT and distribution of pathogens; (2) analysis of risk factors for abdominal infection after LT; (3) follow-up and survival. Follow-up was performed using outpatient examination and tele-phone interview to detect postoperative 1-year survival rate and cases of death up to June 2020. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were described as M(range). Count data were expressed as absolute numbers or percentages. Univariate analysis was conducted using the chi-square test, t test, Mann-Whitney U test and Fisher exact probability. Multivariate analysis was done using the Logistic regression model. The Kaplan-Meier method was used to calculate sruvival time and survival rates. Log-Rank test was used for survival analysis. Results:(1) Abdominal infection after LT and distribution of pathogens: 63 of 356 recipients had abdominal infection after LT, with the overall incidence of 17.70%(63/356). Of the 63 recipients, 41 cases had abdominal infection within postoperative 2 weeks, 17 cases had multi-drug resistant organism infection. A total of 116 strains of bacteria were isolated from 63 recipients with abdominal infection, 52 of which were gram-negative bacteria, 48 were gram-positive bacteria, 16 were fungi. (2) Analysis of risk factors for abdominal infection after LT: results of univariate analysis showed that preoperative model for end-stage liver disease (MELD) score, preoperative serum albumin, preoperative leukocytes, preoperative prothrombin time, preoperative alanine aminotransferase, preoperative aspartate aminotransferase, operation time, volume of intraoperative blood loss, days of postoperative antibiotic use, postoperative renal failure, postoperative delayed graft function,duration of postoperative intensive care unit stay were related factors for abdominal infection after LT ( Z=-2.456, t=-1.982, Z=-3.193, -2.802, -2.336, -2.276, -2.116, -3.217, χ2=15.807, 10.395, 6.750, Z=-4.468, P<0.05). Liver retransplantaiton and postoperative bile leakage were related factors for abdominal infection after LT ( P<0.05). Results of multivariate analysis showed that preoperative MELD score>20 and liver retransplantation were independent risk factors for abdominal infection after LT ( odds ratio=2.871, 12.875, 95% confidence interval as 1.106-7.448, 1.290-128.521, P<0.05). (3) Follow-up and survival: 356 recipients were followed up for 1-66 months, with a median follow-up time of 32 months. The postoperative 1-year overall survival rate of 63 recipients with abdominal infection and 293 recipients without abdominal infection were 84.60% and 97.03%, respectively, showing a significant difference ( χ2=11.660, P<0.05). During the follow-up, 58 recipients died. Conclusion:Preoperative MELD score>20 and liver retransplantation are independent risk factors for abdominal infection after LT.

Objective:To summarize and analyze of the clinical and genetic characteristics of children with nonmuscle myosin heavy chain 9 (MYH9)-related disease (MYH9-RD).Methods:To screen the patients who were first diagnosed as "chronic/refractory immune thrombocytopenia (ITP) " from April 2016 to May 2019 in Beijing Children′s Hospital by genetic and clinical examinations, then the clinical manifestation, laboratory examination and genetics results of 7 children diagnosed with MYH9-RD were collected and summarized retrospectively.Results:Among 7 children diagnosed with MYH9-RD, 3 were males and 4 females. The age of onset was 1.25 (0.41-6.16) years. The course of disease was 2.16 (0.41-8.59) years. The automatic platelet count was (9 (5-30))×10 9/L. All the cases were found with giant platelets under microscope,and the manual platelet count was (70 (30-100))×10 9/L. Four cases had skin hemorrhage or epistaxis and 3 cases had no bleeding. All 7 patients had received first-or second-line therapy of ITP, of whom 1 case received splenic embolization, and all the treatments mentioned above were ineffective. Finally, it was confirmed that all 7 patients had heterozygous missense mutations of MYH9 gene by next generation sequencing (NGS), including 2 pedigrees and 5 sporadic cases. Four sporadic mutations occurred in N-terminal globular head domain (HD), and 1 sporadic case with p.D1424N mutations occurred in the C-terminal tail domain (TD). One of the pedigrees also had p.D1424N mutation. The other familial case had a novel variant with one missense variant p.A44D caused by the c.131C>A transition. One of the two p.R702 mutations had kidney damage, and several relatives of the new p.A44D mutations had deafness. Conclusions:In this study, the spontaneous mutations of seven MYH9-RD were common, and all patients were misdiagnosed as ITP, whereas the bleeding was mild and immunotherapy was ineffective. The suspected disease can be identified earlier by manual visual platelet volume and count, which can be confirmed by genetic testing. It is more important to monitor the development of other organs damage instead of thrombocytopenia. For cases with p.R702 mutations the doctor should be aware of kidney damage, and for the cases with novel mutations p.A44D the doctor should be aware of hearing loss.

Objective:To explore the change characteristics of amino acid levels in neonates, so as to provide theoretical basis for accurate clinical interpretation.Methods:By preliminary screening and diagnosis from 32 855 newborns, 32 843 samples were collected using tandem mass spectrometry to inherited metabolic disease (IMD) scree-ning in Sichuan Province from January to December 2018.Afterwards, according to gestational age (1 363 premature infants, 31 468 full-term infants and 12 overdue infants), blood collection time (3-7 days old, 3 095 cases, 8-28 days old, 1 637 cases, and more than 28 days old, 248 cases) and season (7 737 cases in the first quarter, 11 428 cases in the second quarter, 5 482 cases in the third quarter, and 8 196 cases in the fourth quarter), neonates were divided into different study groups.The difference of amino acid level in each group was compared, and the correlation between various influencing factors and metabolic index was analyzed.Results:(1) The distribution of 11 amino acids [alanine(ALA), arginine(ARG), citrulline(CIT), glycine(GLY), leucine+ isoleucine+ hydroxyproline (LEU+ ILE+ PRO-OH), methionine(MET), ornithine(ORN), phenylalanine(PHE), proline(PRO), tyrosine(TYR), and valine(VAL)] in neonates showed non-normally distribution.(2)The distribution of 11 amino acids in different gestational age were tested by nonparametric test, except for PHE( H=0.61, P>0.05)and TYR( H=2.02, P>0.05), and other indicators were significantly different [ALA( H=187.11, P<0.05), ARG( H=23.60, P<0.05), CIT( H=22.90, P<0.05), GLY( H=85.18, P<0.05), LEU( H=56.42, P<0.05), MET( H=18.74, P<0.05), ORN( H=129.27, P<0.05), PRO( H=344.40, P<0.05), and VAL( H=272.92, P<0.05)]. (3) The distribution of 11 amino acids in different blood collection time were significantly different [ALA( H=65.19, P<0.05), ARG( H=404.48, P<0.05), CIT( H=502.13, P<0.05), GLY( H=1 719.44, P<0.05), LEU( H=396.41, P<0.05), MET( H=199.39, P<0.05), ORN( H=31.26, P<0.05), PHE( H=325.49, P<0.05), PRO( H=70.09, P<0.05), TYR( H=159.29, P<0.05), and VAL( H=102.52, P<0.05)]. (4) The distribution of 11 amino acids in different birth seasons were significantly different [ALA( H=401.37, P<0.05), ARG( H=3 229.03, P<0.05), CIT( H=65.45, P<0.05), GLY( H=597.82, P<0.05), LEU( H=1 120.42, P<0.05), MET( H=10 515.18, P<0.05), ORN( H=1 275.23, P<0.05), PHE( H=2 260.17, P<0.05), PRO( H=319.57, P<0.05), TYR( H=884.37, P<0.05), and VAL( H=1 824.49, P<0.05)]. Conclusion:According to different gestational age, season and blood collection time, the metabolism of amino acids in neonates was different.When using tandem mass spectrometry for detection, appropriate interpretation criteria should be selected based on different conditions.

Objective To quantitatively evaluate the diagnostic value of blood oxygen leveldependent (BOLD) MRI in the diagnosis of different degrees of liver warm ischemia-reperfusion injury (WIRI) in rabbits and evaluate the intervention effect of liposomal prostaglandin E1 (Lipo-PGE1).Methods Seventy healthy adult New Zealand white rabbits were randomly divided into sham -operated group (A0),thermal ischemic groups (A1～A3) and intervention groups (A4～A6).All experimental rabbits were scanned by routine MR and BOLD MRI after 6-hour reperfusion.R2* images were calculated by two radiologists.The levels of alanine aminotransferase (ALT),asparate aminotransferase (AST) and lactate dehydrogenase (LDH) were examined.And liver pathological sectioning was performed.All data were processed by one-way,Spearman's correlation and receiver operating characteristic curve analyses.Results The intraclass correlation coefficient (ICC) was 0.805 of two measurements suggesting that the repeatability of the outcome was decent.R2* values among sham-operated,thermal ischemia and intervention groups were statistically significant (P＜0.05).R2 * values in sham-operated and ischemia groups were statistically significant (P＜0.05).As warm ischemia time elapsed,R2* value showed a rising trend.R2* values in sham-operated and intervention groups were statistically significant (P＜0.05).R2* values of sham-operated group at the same timepoint of thermal ischemia and intervention groups were statistically significant (P＜0.05).Under the same ischemic time,R2* values of intervention groups were smaller than those of thermal ischemia groups.With the prolongation of ischemia time,reduction of R2* values became more pronounced.However,it did not reach the level of A0 group.R2* values were significantly positively correlated with ALT,AST and LDH (r＞0.5,P＜0.05).ROC analysis indicated that R2* had an excellent diagnostic performance.Conclusions BOLD MRI may be applied for noninvasive assessment of liver ischemia-reperfusion injury in different degrees.Lipo-PGE1 alleviates ischemia -reperfusion injury and BOLD MRI can evaluate the relieving degree of Lipo-PGE1.

Objective To investigate the risk factors and prognosis of acute kidney injury (AKI) after orthotopic liver transplantation (OLT).Methods The retrospective case-control study was conducted.The clinical data of 127 patients who underwent OLT in the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to December 2015 were collected.Of 127 patients,24 were complicated with postoperative AKI,including 17 in grade 1,5 in grade 2 and 2 in grade 3,and 103 were not complicated with AKI.AKI after OLT was treated according to the diagnostic criteria of AKI from 2012 guidelines of Kidney Disease:Improving Global Outcomes (KDIGO).Observation indicators:(1) risk factors analysis affecting AKI after OLT;(2) comparison of postoperative recovery in patients with different AKI grade;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed up to July 2017.Measurement data with nornal distribution were represented as x±-s,and measurement data with skewed distribution were described as M (range).Univariate analysis was done using the t test and rank sum test.Comparisons of count data and univariate analysis were done using chi-square test or Fisher exact probability.Multivariate analysis was done using the logistic regression model.The survival rate and curve were respectively calculated and drawn by the KaplanMeier method,and Log-rank test was used for survival analysis.Results (1) Risk factors analysis affecting AKI after OLT:results of univariate analysis showed that age,combined hypertension,preoperative Child-Pugh score,preoperative model for end-stage liver disease score (MELD),preoperative hemoglobin,preoperative serum albumin,preoperative blood urea nitrogen,preoperative glomerular filtration rate,preoperative prothrombin time,operation time,inferior vena cava occlusion time,duration of anhepatic phase,volume of intraoperative blood loss,total volume of intraoperative blood transfusion,volumes of intraoperative plasma and red blood cells transfusion,duration of postoperative ICU stay,use time of postoperative vasoactive drugs,time of postoperative mechanical ventilation,cases with postoperative infection,body mass index of donor and donor liver cold-ischemia time were related factors affecting occurrence of AKI after OLT (t =4.154,x2 =8.482,t =5.129,3.694,1.294,9.223,5.418,Z=4.287,t=2.105,5.168,8.182,10.042,Z=1.074,0.664,6.274,3.712,1.289,t=1.056,x2 =10.617,t=2.447,3.371,1.476,P＜0.05).Results of multivariate analysis showed that age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time were independent factors affecting occurrence of AKI after OLT [odds ratio (OR) =0.812,0.866,1.392,1.001,0.516,95％ confidence interval:0.717-0.919,0.751-0.997,1.104-1.755,1.000-1.001,0.282-0.944,P＜0.05].(2) Comparison of postoperative recovery in patients with different AKI grade:cases with complete recovery,partial recovery and chronic renal failure were respectively 14,3,0 in 17 patients with grade 1 of AKI and 3,2,0 in 5 patients with grade 2 of AKI and 0,1,1 in 2 patients with grade 3 of AKI,with a statistically significant difference (x2=14.140,P＜0.05).(3) Follow-up and survival situations:127 patients were followed up for 9-44 months,with a median of 23 months.The 1-year overall survival rate of 127 patients was 95.3％.During the follow-up,22 patients died,including 9 with multiple organ failure,8 with primary disease recurrence and 5 with respiratory complication.The median overall survival time after OLT was 36 months in 24 patients with AKI and 40 months in 103 patients without AKI,with no statistically significant difference (x2=3.033,P＞0.05).Conclusion Age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time are independent factors affecting occurrence of AKI after OLT,and there is better recovery in patients with grade 1 of AKI.

Objective To explore the effect of psychotherapy in patients with optic papilledema undergoing optic nerve sheath fenestration (ONSF).Methods Using convenience sampling method,a total of 64 patients with intracranial hypertension and optic papillary edema who were diagnosed by Ophthalmology Department of Xuanwu Hospital of Capital Medical University from 2013 to 2017 were selected as the subjects of study.All the subjects were randomly divided into two groups,with 32 patients in each group.Patients in the control group received routine ophthalmic nursing.The patients in the observation group were given six-step psychological intervention.Self-rating Anxiety Scale (SAS) were applied within 2 days after admission and before discharge to evaluate the patients.Results The score of SAS before discharge in the observation group was (46.28±4.48),which was lower than that in the control group (56.84±8.25),and the difference was statistically significant (t=6.363,P＜0.01).Conclusions Relevant psychotherapy can improve the anxiety of patients,so that patients can cooperate well with the treatment,which is worthy of clinical application.

Objective:To explore the effect of delphinidin on breast cancer and the underlying mechanisms.Methods:Human epidermal growth factor receptor-2 (HER-2) positive breast cancer cells MDA-MB-453 were treated by delphinidin.Proliferation of MDA-MB-453 cells was detected by CCK-8 after 48 h.TdT-mediated dUTP nick end labeling (TUNEL) assay and Western blot were used to explore apoptotic status for MDA-MB-453 cells.Fluorescence dot assay,immunofluorescence,and Western blot were used to identify autophagy in breast cancer cells.Results:Delphinidin suppressed proliferation of MDA-MB-453 cells.Delphinidin increased the number of TUNEL positive cells.Delphinidin downregulated the expression of caspase-3 and caspase-9,while upregulated the expression of cleaved caspase-3 and cleaved caspase-9 in a dose-dependent manner.Delphinidin enhanced the number of GFP-LC3 punctate dots,LC3 immunofluorescence dots and the expression of LC3-Ⅱ and ATG5.Delphinidin inhibited the expression of proteins in mTOR signaling pathway,induding AKT,mTOR,eIF4E and p70s6k.Conclusion:Delphinidin induced apoptosis and autophagy by inhibition of AKT/mTOR pathway in HER positive breast cancer cells.