Objective To investigate the mechanism by which human hypoxia up-regulation 1(HYOU1)regulates pancreatic cancer development.Methods Bioinformatic and immunohistochemical staining analyses of HYOU1 ex-pression level in pancreatic tumor tissues,normal and paracancerous tissues and its correlation with patients'surviv-al.Quantitative real-time PCR(qPCR)and Western blot were used to clarify the expression level of HYOU1 in a number of human pancreatic ductal adenocarcinoma cell lines and a normal human pancreatic ductal cell line.Two cell lines with the highest expression levels of HYOU1,BXPC-3 and Panc-1,were selected to knock out HYOU1 by CRISPR-Cas9,and then cell survival,proliferation and migration of these cells were examined by cell counting kit-8(CCK-8),colony formation assay and wound healing experiment separately,as well as apoptosis was detected by flow cytometry.Subsequently,the protein levels of the PI3K/Akt signaling including PI3K,p-PI3K,Akt,and p-Akt were detected by Western blot in parental and HYOU1-ablated BXPC-3 and Panc-1 cells.Cell proliferation was also examined in HYOU1-ablated cells after treatment of recilisib,an activator of the PI3K/Akt pathway.Results The expression of HYOU1 in pancreatic tumor tissues was significantly higher than that in normal tissues,and the patients with high expression of HYOU1 had a much shorter survival compared to the patients with low HYOU1(P＜0.01).Immunohistochemical staining of pancreatic cancer specimens showed that the expression of HYOU1 was higher in tumor tissues than in paracancerous tissues(P＜0.01).The mRNA and protein levels of HYOU1 were higher in all pancreatic cancer cell lines compared to the human normal pancreatic ductal cell(P＜0.001,P＜0.01).HYOU1 ablation inhibited BXPC-3 and Panc-1 cells survival,proliferation and migration,and promoted early cell apoptosis.In addition,loss of HYOU1 decreased PI3K/Akt signaling activity,whereas the PI3K/Akt ac-tivator Recilisib reversed the effects of HYOU1 ablation on cell survival and proliferation.Conclusion HYOU1 promotes pancreatic cancer progression by activating the PI3K/Akt signaling pathway.

Objective: To report an investigation of a family cluster of coronavirus disease 2019 ( COVID-19 ) in Ningbo, so as to provide reference for the prevention and control measures. Methods: According to the COVID-19 Prevention and Control Program ( fourth version ) , an epidemiological investigation was conducted to collect the demographic information, clinical features and exposure history, to find the close contacts, and to figure out the source and route of infection. Results: Twelve confirmed cases and one asymptomatic case were reported. The attack rate was 16.05%. Among them, five were males and eight were females; the age ranged from 11 to 85 years old, with a median of 39 years old; most had mild symptoms. The incubation period was 2-13 days, with a median of 6.5 days. The first case ( Case 1 ) developed the symptoms on January 22, and had close contact with Zhang, an asymptomatic case, on January 20. Zhang was related to a cluster in the Buddhist assembly on January 19. Case 1, who caused the spread of the epidemic among family members, participated in several family visits and dinners from January 22 to 27 with other 24 families, resulting in six secondary cases and six third-generation cases. There were 54 close contacts except the family members, no infection was found. Conclusion This family cluster may result from the close contact with an asymptomatic case, and then spread within families through having dinners and living together.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

Objective:To explore the feasibility of quantitative evaluation of extracellular volume (ECV) fraction in acute ST-segment elevation myocardial infarction (STEMI) by dual-layer spectral detector CT.Methods:The clinical and imaging data of 20 patients with STEMI who underwent cardiac contrast-enhanced CT and MRI from January to October 2019 in Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed.The dual spectral detector was used in the enhanced CT scan of the coronary artery with retrospectively gate and the late iodine enhancement with prospective gate. Conventional image and holographic spectral image were obtained by iterative and spectral reconstruction. The short axis image of the heart matched with MR image was obtained by multiplanar reconstruction. Based on the data of spectral based image, the IDD map was reconstructed for the calculation of myocardial CT-ECV during the late iodine enhancement. ECV of infarcted myocardium, salvageable myocardium and remote myocardium based on CT and MRI were calculated respectively. Bland-Altman consistency test and intra group correlation coefficient analysis (ICC) were used to compare the consistency of two measurements and different methods. The correlation between CT-ECV and MRI-ECV was compared by Spearman method.Results:The CT-ECV values of infarcted, salvageable, and remote myocardium were 51.21 (49.27, 53)%, 38.64 (36.17, 40)%, and 51.21 (49.27, 53)%, respectively. The difference was statistically significant ( H= 43.17, P<0.01). The CT-ECV value of infarcted myocardium was significantly higher than that of salvageable myocardium and remote myocardium ( Z=-24.60, 35.40, P<0.01), but there was no significant difference between salvageable myocardium and remote myocardium ( Z= 10.80, P=0.15). The T 1 values of infarcted myocardium, salvageable myocardium and remote myocardium were (1 554.85±70.94), (1 443.85±67.28) and (1 307.05±91.73) ms respectively, the difference was statistically significant ( F=51.35, P<0.01). The T 1 value of infarcted myocardium was higher than that of salvageable myocardium and remote myocardium ( t=-5.07, 9.55, P<0.01), and salvageable myocardium was significantly higher than that of remote myocardium ( t=5.38, P<0.01). The MRI-ECV values of infarcted myocardium, salvageable myocardium and remote myocardium were 55.00 (49.27, 57.75)%, 33.50 (29.00, 35.00)%,and 27.00 (26.00, 29.00)%, respectively. The difference was statistically significant ( Z= 47.12, P<0.01). MRI-ECV of infarcted myocardium was significantly higher than that of salvageable myocardium and remote myocardium ( Z=37.45, -20.30, P< 0.01), and salvageable myocardium was significantly higher than that of remote myocardium ( Z = 17.15, P<0.05). The difference between CT-ECV and MRI-ECV measured by two physicians was good. The bias of Bland-Altman analysis was -0.1% (95% CI:-5.5%-5.2%), 0.8% (95% CI:-9.8%-8.2%), and the ICC values were 0.92 and 0.94, respectively. The bias of Bland-Altman analysis in CT-ECV and MRI-ECV consistency test was 4.00% (95% CI:-9.0%-16.9%) and ICC value was 0.88, which had a good correlation ( r=0.75, P=0.001). Conclusions:The iodine density based ECV fromdual-layer spectral detector CT can be used to quantitatively evaluate the changes of extracellular space after acute STEMI, which is helpful to quantitatively evaluate the histological changes after myocardial ischemia.