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 examine the occurrence of complications in elderly patients who have undergone radical surgery for colorectal cancer.Additionally, this study aims to identify the various risk factors associated with these complications.Methods:This study included elderly patients with colorectal cancer who underwent radical surgery at Beijing Hospital between January 2013 and December 2020.These patients were divided into two groups based on their age.In this study, we examined a total of 906 patients who underwent surgery, with 695 patients under the age of 80 and 211 patients aged 80 and above.We classified postoperative complications into two categories: medical and surgical complications.Our analysis compared comorbidities, clinicopathological factors, perioperative variables, and postoperative morbidity and mortality between the two age groups.We utilized both univariate and multivariate analyses to identify any potential risk factors for postoperative morbidity.Results:When comparing patients under 80 years old to those aged 80 or older, it was found that the latter group had a lower body mass index, worse ASA scores, and more comorbidities.Additionally, the proportion of elderly patients with right colon cancer, pT3-4, and pN+ disease was higher compared to those under 80 years old.Furthermore, the elderly patients aged 80 or older had a lower rate of laparoscopic surgery compared to those under 80 years old.The study found that elderly patients aged 80 years and older had significantly shorter operation times compared to those younger than 80 years[(191.0±70.6)min vs.(214.0±83.3)min, t=3.642, P<0.001]. However, the overall complication rate was higher in the elderly group(32.7%)than in the younger group(22.6%)( χ2=8.839, P=0.004). Upon further analysis, it was found that medical complications increased significantly(20.9% vs.7.5%, χ2=30.547, P<0.001), whereas the rate of surgical complications did not show any statistical difference(15.6% vs.16.4%, χ2=0.069, P=0.832). The mortality rate during the perioperative period was found to be significantly higher in elderly patients aged 80 years and above compared to those below 80 years(1.9% vs.0.3%, χ2=6.316, P=0.029). Further analysis revealed that age was an independent risk factor for medical complications( HR=2.822, 95% CI: 1.804-4.414, P<0.001). Laparoscopic surgery has been shown to significantly decrease surgical complications( HR=0.475, 95% CI: 0.317-0.711, P=0.001). However, if the operation time exceeds 200 minutes, there is a significant increase in surgical complications( HR=1.942, 95% CI: 1.278-2.888, P=0.002). Conclusions:The incidence of postoperative medical complications in very elderly patients with colorectal cancer who undergo radical surgery has risen, although the rate of surgical complications has remained steady.Radical surgery for elderly patients with colorectal cancer is both safe and feasible, but it is important to prioritize the prevention and management of medical complications.

Objective To investigate the role of nitric oxide synthase(NOS)in the regulation of myocardial ischemia-reperfusion(IR)injury in ovariectomized(OVX)rats.Methods A total of 132 female SD rats were subjected,and 48 of them were randomly divided into sham operation group,IR group,OVX group and combined group,with 12 in each group.In order to explore the role of endothelous NOS(eNOS)and inducible NOS(iNOS)in ovariectomization increasing myo-cardial IR injury,another 84 mice were divided into negative sham group,negative IR group,nega-tive combined group,eNOS+IR group,eNOS combined group,iNOS small interfering RNA(si-iNOS)+IR group and si-iNOS combined group,with 12 in each group.The mice of the corre-sponding groups were injected with adeno-associated virus(AAV)overexpressing eNOS or knoc-king down iNOS via tail vein before OVX modeling.Myocardial infarct size,serum levels of lac-tate dehydrogenase(LDH)and creatine phosphokinase isoenzyme(CK-MB),LVEF,LVFS,and expression levels of eNOS and iNOS in the myocardial tissues were measured.Results The com-bined group had significantly increased level of iNOS in myocardium,larger myocardial infarct size and elevated serum LDH and CK-MB levels,but decreased myocardial expression of eNOS and LVEF and LVFS values than the IR group(P＜0.05).When compared with the negative combined group,the myocardial infarct size and serum LDH and CK-MB levels were decreased[(23.51±3.22)％and(26.21±2.93)％vs(58.78±5.42)％,(176.31±15.48 and 169.52±17.12 vs 328.85±37.12 U/L,35.41±6.41 and 34.77±5.94 vs 88.73±9.14 U/L,P＜0.05],and the LVEF and LVFS values were increased[(41.31±3.12)％and(42.09±3.41)％vs(30.77± 2.15)％,(21.47±1.57)％and(21.32±1.42)％vs(15.92±1.33)％,P＜0.05]in the eNOS com-bined group and si-iNOS combined group.Conclusion The decrease of eNOS expression and in-crease of iNOS expression are related to the aggravation of myocardial IR injury in OVX rats.

Objective:To investigate the relationship between the changes of default network topology properties of brain function and cognitive function in patients with end-stage renal disease (ESRD).Methods:A total of 31 patients with ESRD were enrolled in the Department of Nephrology, Changzhou Second Hospital Affiliated to Nanjing Medical University from January 2019 to December 2020, and 18 healthy persons were included in the same period as the control group.The cognitive function was evaluated with the Montreal cognitive assessment (MoCA) and trail making tests, and then the subjects were examined by resting-state functional magnetic resonance imaging (rs-fMRI). After preprocessing, the brain functional network was constructed and the topology properities of the network were calculated.The SPSS 20.0 software was used for statistical analysis.Independent sample t-test, chi square test and Pearson correlation analysis were used for data statistics. Results:(1) The score of MoCA in the ESRD group(23.37±1.77) was significantly lower than that in the healthy control group(27.94±1.13)( t=9.537, P<0.001). (2) The levels of Eglobal, Elocal, Cp and Sigma in ESRD group ((0.129±0.025), (0.148±0.040), (0.188±0.046), (1.593±0.650)) were significantly lower than those in healthy control group ((0.160±0.040), (0.212±0.024), (0.276±0.049), (2.004±0.864))( t=3.591, 7.474, 7.058, 2.034, all P<0.05). The Lp value of the ESRD group (8.131±1.905) was significantly higher than that of the control group (6.777±2.150)( t=2.583, P< 0.05). The node efficiency values of bilateral dorsolateral superior frontal gyrus, left middle frontal gyrus, bilateral posterior cingulate gyrus, right hippocampus, left superior marginal gyrus, bilateral angular gyrus and bilateral cuneate anterior lobe in ESRD group ((0.133±0.071), (0.201±0.047), (0.211±0.106), (0.175±0.066), (0.276±0.113), (0.122±0.146), (0.042±0.075), (0.171±0.027), (0.154±0.078), (0.240±0.095), (0.161±0.056))were lower than those in the healthy control group((0.312±0.075), (0.289±0.091), (0.277±0.132), (0.284±0.053), (0.368±0.063), (0.231±0.227), (0.120±0.162), (0.296±0.064), (0.310±0.186), (0.318±0.066), (0.286±0.103))( t=2.107-9.436, all P<0.05). (3)Pearson correlation analysis showed that the node efficiency values of bilateral posterior cingulate gyrus and right hippocampus in ESRD group were positively correlated with the score of MoCA( r=0.36, 0.49, 0.53, all P<0.05). Conclusion:The topological structure of brain functional network is abnormal in ESRD patients, which can affect the cognitive function of patients.

Objective:To analyze the risk factors for postoperative adverse cardiovascular events(PACE)in elderly patients after treatment with colectomy.Methods:Clinical data of 720 elderly patients aged 65 years and over treated with colectomy from January 2012 to December 2019 in Beijing Hospital, National Center of Gerontology were analyzed retrospectively.According to the occurrence of PACE(non-fatal myocardial infarction, acute coronary syndrome, arrhythmia, heart failure/cardiac insufficiency, etc.), the cases were divided into the PACE group and the non-PACE group.Clinical data of the two groups were compared and the risk factors for PACE were investigated using multivariate Logistic regression.Results:The overall incidence of PACE was 5.8%(42/720). Statistically significant differences were found between the PACE and non-PACE groups in patient age, the American Society of Anesthesiologists(ASA)classification, the Goldman index score and comorbidities(coronary heart disease, arrhythmia, old myocardial infarction, chronic renal insufficiency), preoperative serum levels of BNP and D-dimmer, and postoperative length of stay( P<0.05). A further multivariate Logistic regression analysis showed that significant differences existed between the groups in NYHA Ⅲ and Ⅳ, ASA Ⅲ and old myocardial infarction, with the overall risk of PACE increasing by 4.017, 2.320 and 2.746, respectively. Conclusions:The incidence of PACE following colectomy is related to multiple perioperative factors.For elderly colorectal cancer patients with one or more of the above risk factors, we should be on high alert for PACE during hospitalization.

Objective:To investigate the short-term and long-term efficacy of laparoscopic surgery for colorectal cancer in elderly patients aged 80 and over.Methods:This study included patients aged 80 and over with sigmoid or rectal cancer who had undergone radical surgery in Beijing Hospital between January 2013 and December 2020.Of the enrolled patients, 47 underwent laparoscopic surgery, and 44 received open surgery.After 1∶1 propensity score matching(PSM), there were 32 cases in each group.Patient clinicopathological characteristics, surgery data, post-operative outcomes and long-term survival were compared.Results:Before PSM, there were significant differences in sex composition and tumor locations between the open surgery and laparoscopic surgery groups.After PSM, there was no significant difference in clinicopathological characteristics between the two groups.Before and after PSM, the operative time for laparoscopic surgery was statistically longer than that for open surgery.The intraoperative blood loss, the postoperative complication rate and the number of harvested lymph nodes were not significantly different between the two groups before and after PSM.Before and after PSM, the postoperative hospital stay in the laparoscopic operation group was shorter than that in the open surgery group, but the difference was not statistically significant.Before PSM, the 1-year, 3-year and 5-year survival rates of the open surgery group were 92.4%, 69.5% and 58.1%, respectively, and the 1-year, 3-year and 5-year survival rates of laparoscopic group were 91.3%, 79.8% and 69.5%, respectively.There was no significant difference in overall survival between the two groups before PSM( χ2=0.591, P=0.422). After PSM, the 1-year, 3-year and 5-year survival rates in the open surgery group were 89.3%, 67.1% and 52.2%, respectively, and the 1-year, 3-year and 5-year survival rates in the laparoscopic surgery group were 90.6%, 74.3% and 65.0%, respectively.There was no significant difference in the overall survival between the two groups after PSM( χ2=1.316, P=0.251). Conclusions:For elderly colorectal cancer patients aged 80 and over, laparoscopic surgery and open surgery have similar rates of complications and long-term survival.This study provides evidence for the safety of laparoscopic surgery.Further prospective randomized controlled clinical trials are needed to confirm these findings.

Objective:To evaluate the objective imaging markers of cognitive impairment in patients with end-stage renal disease by MRI intravoxel incoherent motion.Methods:A total of 40 patients with ESRD were enrolled in the Department of Nephrology, Changzhou Second Hospital Affiliated to Nanjing Medical University from January 2019 to August 2020, and 24 healthy controls were prospectively enrolled at the same time.All subjects performed with MRI scan were collected, and the slow apparent diffusion coefficient (ADC slow) of the corresponding brain regions were obtained .The cognitive function was evaluated by the Montreal cognitive assessment scale (MoCA). Two-sample t test was used to analyze the difference of ADC slow and cognitive score between the two groups.Pearson correlation analysis was performed among the cognitive function score of end-stage renal disease and ADC slow value. Results:(1) The score of the intelligence test scale in the ESRD group (23.30±1.76) was significantly lower than that of the healthy control group (27.92±1.00) ( P<0.01). The ADC slow values of bilateral frontal lobe, hippocampus, and insula brain areas (respectively(0.648±0.035), (0.633±0.043), (0.762±0.043), (0.756±0.042), (0.792±0.048), (0.776±0.054))in the ESRD group were significantly higher than those in the healthy control group ((0.600±0.039), 0.610±0.037, (0.725±0.059), (0.711±0.054), (0.740±0.063), (0.716±0.051)) ( P<0.01). (2) Pearson correlation analysis showed that the ADC slow values of bilateral insula and right hippocampus in the ESRD group were negatively correlated with MoCA scales ( r=-0.38, -0.38, -0.66, all P<0.05). Conclusion:ADC slow value in IVIM can better reflect the changes of cognitive function impairment in ESRD patients.

OBJECTIVE: To explore the mechanism of a false-negative result from karyotyping of chorionic villi cells for a trisomy 13 fetus featuring multiple malformations. METHODS: For a fetus with multiple malformations by ultrasonography and a 46,XY karyotype by chorionic villi analysis, amniocytes were further analyzed with quantitative fluorescence PCR (QF-PCR), G-banded karyotyping and chromosomal microarray analysis (CMA). Meanwhile, non-invasive prenatal testing (NIPT) was conducted on peripheral blood sample from the pregnant woman to determine the chromosomal composition of cytotrophoblast. After induction of labor, common aneuploidies in placenta and fetal tissue were also analyzed by QF-PCR. RESULTS: QF-PCR, chromosomal karyotyping and CMA analysis of the amniocytes all suggested complete trisomy 13 (47,XY,+13) in the fetus. NIPT also suggested existence of fetal trisomy 13. QF-PCR analysis of the placenta and fetal tissues revealed that cells derived from the maternal surface and right side of fetal surface harbored mosaic trisomy 13, while those derived from other sites of fetal surface of the placenta, umbilical cord, amniotic membrane and fetal muscle tissue harbored trisomy 13. CONCLUSION Karyotyping of long-term cultured chorionic villus sample may give rise to false negative results due to placental mosaicism. To ensure accurate prenatal diagnosis, discordance between karyotyping of chorionic villi cells, fetal ultrasound and NIPT result should be verified by amniocentesis or cordocentesis and application of multiple cytogenetic and molecular techniques.

OBJECTIVE：To provid e reference for pharmaceutical workers to better understand Novel Coronavirus Infection ： Expert Consensus on Guidance and Prevention Strategies for Hospital Pharmacists and the Pharmacy Workforce （hereinafter referred to as “expert consensus ”），and to apply and practice in specific work ，so as to give full play to the role of pharmacists to help fight the epidemic.METHODS ：The background of the formulation and revision of the expert consensus were introduced ，and its main contents and viewpoints were interpreted. RESULTS & CONCLUSIONS ：The text of expert consensus is divided into 8 parts，mainly including disease diagnosis and treatment [SARS-CoV- 2 infection related background ，clinical manifestations and diagnosis， treatment]，hospital pharmacy （prevention and control strategy ，work guidance ），drug and facility support management（key drug/facility/equipment support ，management and use of the drug in special circumstances ），information sources and related resources ，etc.，which comprehensively and detailedly provide information ，guidance and strategies for coronavirus SARS-CoV-2 infection prevention and control to play the role of pharmacists in hospital pharmacy well ，do well in the protection of staff in different pharmaceutical posts ，drug security work in response to epidemic situation ，and develop pharmaceutical care. So far，the understanding of SARS-CoV- 2 in the pharmaceutical industry is relatively limited. Based on the accumulated experience and progress in epidemic prevention and control ，the expert consensus will be updated and improved continuously ，so as to provide guidance and help for hospital pharmaceutical personnel.

Objective To investigate the effect of ERH gene knockdown on the proliferation and apoptosis of human bladder cancer T24 cells. Methods T24 cells infected by lentivirus with interference on ERH gene sequence were cloned to establish stable T24 cells clone in ERH gene suppression. The expression of ERH mRNA gene in bladder cancer was detected by using quantitative real time polymerase chain reaction (qPCR). The effects of ERH knockout on the cell proliferation and apoptosis were examined by using methylthiazolyl tetrazolium (MTT) assay, colony formation assay and flow cytometry. The effect of ERH knockout on the tumorigenic effect of T24 cells in vivo was verified by subcutaneous tumor formation in nude mice. Results After lentiviral transfection, qPCR results showed that the knockdown effect of ERH mRNA in ERH normal group (untreated T24 cells) was better than that in ERH gene knockdown group, and the difference was statistically significant [(1.006±0.126) vs. (0.079±0.007); t=12.72, P=0.0002]. After knocking out ERH gene, MTT assay showed that the proliferation ability of T24 cells in ERH gene knockdown group was weakened compared with ERH normal group, and the difference was statistically significant [A490 value: (0.13±0.00) vs. (0.66±0.01);t=104.61, P<0.0001]. Colony formation assay indicated that the ability of clone in ERH normal group was weakened compared with ERH gene knockdown group [(10.5 ±1.2) vs. (196.4 ±4.0); t= 73.63, P< 0.0001]. Flow cytometry showed that the cell apoptosis rate in ERH gene knockdown group was higher than that in ERH normal group [(11.0 ±0.5) ％ vs. (4.2 ±0.5) ％; t= 16.06, P<0.0001]. Imaging results of subcutaneous tumor formation in nude mice showed that the total fluorescence intensity of the tumor area in ERH gene knockdown group was (4.67 ±0.59) × 1010 μW/cm2, and the corresponding part in ERH normal group was (9.54±4.20) × 1010μW/cm2 (t=3.64, P=0.0051);tumor weight in ERH gene knockdown group was (0.80±0.62) g, and in ERH normal group was (1.79±0.71) g (t=3.33, P=0.0037). Conclusion ERH gene knockout can inhibit the proliferation of human bladder cancer T24 cells, and promote the cell apoptosis.