Objective:To detect the expression of L-type amino acid transporter 1(LAT1)in non-Hodgkin's lymphoma(NHL)tissues,and analyze its effect on clinicopathological characteristics and prognosis of patients.Methods:A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected.The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features(including sex,Ann Arbor stage,extranodal infiltration,Ki-67).The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression.Receiver operating characteristic(ROC)curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality,and analyzing the effect of percentage of LAT1-positive cells on survival rate.Results:LAT1 was positively expressed in NHL tissue.The high expression rate of LAT1 in Ann Arbor stage Ⅲ and Ⅳ groups were higher than that in Ann Arbor stage Ⅰ group,that in extranodal infiltration group was higher than non-extranodal infiltration group,and that in Ki-67 positive expression group was higher than Ki-67 negative expression group(all P＜0.05).The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7％,which was lower than 91.2％in low-LAT1 expression group(P＜0.05).Ann Arbor stage Ⅲ and Ⅳ,extranodal invasion,Ki-67 positive expression and increased expression of LAT1(LAT1-positive cell percentage score ≥ 2)were risk factors for mortality.The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6％,and the area under the ROC curve was 0.905(95％CI:0.897-0.924).The 3-year survival rate of high-LAT1 level group(the percentage of LAT1-positive cells ≥ 45.6％)was 50.00％,which was lower than 78.26％of low-LAT1 level group(P＜0.05).Conclusion:The expression level of LAT1 in NHL tissue increases,which affects Ann Arbor stage and extranodal infiltration of patients.LAT1 is a risk factor for death.

Objective To observe the value of contrast-enhanced mammography(CEM)for differentiating benign and malignant breast lesions with calcifications.Methods Data of 116 female patients with 132 breast imaging reporting and data system(BI-RADS)category 4 to 5 lesions were retrospectively analyzed.The lesions were divided into malignant group(n=86)and benign group(n=46)according to the pathologic results.The morphological manifestations of calcification and their distributions were classified into high or low risk,and the combined risk typing of calcifications was assessed according to these two.Finally,an overall risk typing of CEM was obtained through combining the combined risk type of calcifications and accompanied enhancement or not.Then receiver operating characteristic(ROC)curves were drawn,the area under the curves(AUC)were calculated,and the efficacy of the above indexes for differentiating benign and malignant breast lesions with calcifications were evaluated and compared.Results Significant differences of morphology,distribution and accompanied enhancement were found between groups(all P＜0.05).The AUC of morphology risk,distribution risk,the combined risk of calcification,accompanied enhancement and CEM overall risk for differentiating benign and malignant breast lesions with calcifications was 0.709,0.678,0.774,0.800 and 0.875,respectively,of CEM overall risk was higher than that of the others(all P＜0.05).Conclusion CEM overall risk type obtained through integrating morphology and distribution manifestations of calcifications and enhancement type could improve the efficiency of CEM for differentiating benign and malignant breast lesions with calcifications.

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ² test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.
Humans ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; China ; Nucleic Acids

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

In recent years, laparoscopic surgery and robotic surgery have been widely used, and various intraoperative image navigation systems have also developed rapidly. However, the liver itself has a complex vessel and duct system, which increase the difficulty of liver surgery. The augmented reality image navigation system combines the three-dimensional reconstructed image of the liver with the real liver anatomy, which presents the specific relationship between the tumor location and the surrounding vessels for the surgeon. Compared with other intraoperative image navigation methods, augmented reality has its unique advantages. This paper provides an overview of current advances in registration technology in augmented reality image navigation system, and focuses on its applications in liver surgery, including laparoscopic surgery and robotic surgery. Finally, the technological problems and difficulties still faced at present are summarized, and future directions worth studying in this field are proposed.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Herpes simplex keratitis(HSK), caused by the infection of herpes simplex virus type Ⅰ(HSV-1)in cornea, is a global blinding corneal disease. After the primary infection in ocular surface, HSV-1 is transported into trigeminal ganglion and establishes the life-lasting latency, and it results in recurrent keratopathy. In the process of studying the latent mechanism of HSV, it has been gradually recognized that both the virus itself and the host response regulate the latent process of HSV. In recent years, a large number of research results have been obtained on the molecular mechanisms of invasion, immunity, latency and recurrence of neurotropic viruses, which provide new ideas for the prevention and treatment of HSK. In the present review, the recent progress of HSV latency mechanism in trigeminal ganglion after the primary infection in corneal surface was introduced, and the unsolved basic and clinical problems in HSK were discussed.

Background: Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. Objectives: The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. Methods: BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. Results: The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4 + T cells were observed in mice immunized with VLPs. Conclusions The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.

Aim To investigate the effect of microinjection of EX527, a selective SIRT1 antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced conditioned place preference (CPP), and to explore the role of CREB/BDNF in it. Methods The cannulas were implanted bilaterally in the VLO of rats by brain stereotaxis surgery, and the model of morphine-induced CPP was established. The behavioral experiment consisted of four stages:habituation (d 1), pre-test (d 2-4), conditioning training (d 5-14) and test (d 15). At the stage of conditioning training, EX527 (1 μL, 5 g·L

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL^-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.