Objective To screen cardiac-specific short-acting peptides on live myocardial slices using phage display technology,so as to improve the targeted delivery efficiency of drugs in myocardium and provide effective candidates for the targeted therapy of Duchenne muscular dystrophy (DMD) and other cardiomyopathies.Methods Myocardial tissue slices were prepared and cultured in vitro.The protein activities of the tissues were examined by immunohistochemistry.The in vitro cultured myocardial tissue slices were co-incubated with phage library (1×1012 pfu),and the phages that bound to the myocardium were recovered and amplified.The cardiac-specific targeting phages were identified by five rounds of in vitro phage biopanning.The candidate phage-related insertion sequence was sequenced,and the in vivo tissue distribution of the highly enriched phages was verified.Results A platform for in vitro culturing of live myocardial slices was established.Myocardial slices with good biological activity were obtained.After 48 hours of culturing,the normal expression and localization of Dystrophin protein were detected.Using phage library,candidate phages were screened after five rounds of phage biopanning.The results of the sequencing analyses and in vivo tissue distribution verification indicated that the selected candidate phages showed significant enrichment in myocardium and skeletal muscle,and showed low levels in liver and kidney tissues.Conclusions The candidate phages showed higher binding efficiency in both myocardium and skeletal muscle,indicating that the candidate peptides had myocardial targeting property,and that can provide a new method for myocardial targeting therapy of DMD.

AIM:This study continuously monitors the hemodynamic changes in conscious and anesthetic rats during rapid ascent to high altitude to investigate whether there is difference between the 2 conditions and discuss the rela-ted underlying mechanism.METHODS: Sprague-Dawley rats were randomly divided into conscious group, anesthetic group, anesthetic-5000-control ( A-5000-control) group, anesthetic-5000-aminoguanidine ( A-5000-AG) group, conscious-5000-control ( C-5000-control ) group and conscious-5000-aminoguanidine ( C-5000-AG ) group.The rats in anesthetic group and conscious group were kept in a hypobaric chamber, in which the simulated altitude was increased from 2 260 m to 5 000 m at 2 m/s, and the rats in other 4 groups were at 5 000 m.The system arterial pressure ( Psa) , central venous pressure ( CVP) , heart rate ( HR) and breathing rate ( BR) were directly and continuously displayed and digitally recorded by a high-performance data acquisition (PowerLab 16/35, AD Instruments) at 200 Hz.RESULTS: The HR and BR in the conscious rats were higher and MAP was lower than those in the anesthetic rats obviously.A significant decrease in mean arterial pressure ( MAP) in conscious and anesthetic groups was observed following the increase in the altitude levels, and the net decrease in MAP in conscious group was significantly greater.Additionally, HR in the conscious rats was sig-nificantly lower at 5 000 m than that of the initial level.The rats in C-5000-AG group and A-5000-AG group showed a sig-nificant increase in the arterial pressure after the intravenous injection of AG, a selective inhibitor of inducible nitric oxide synthase ( iNOS) , and no marked change of HR and BR was found.CONCLUSION: Blood pressure and HR decrease during rapid ascent to high altitude, while the change of BR is not obvious.The mechanisms of self-safety would be trig-gered in the early stage of hypoxia, which activates iNOS and then leads to a larger number of nitric oxide.Plentiful NO di-astolizes the vessels to improve the ventilation-perfusion mismatch and lower the blood pressure.When the altitude arise to 5 000 m, even more earlier, a decompensatory stage may occur in the body, leading to decreased HR and blood pressure further more than those in the anesthetic rats.Due to the effects of pentobarbital sodium, the depression of blood pressure requires a lag period and the net decrease in MAP is less than that in the conscious rats.Therefore, hemodynamic changes during rapid ascent to high altitude in conscious rats are more comprehensive and authentic.

Objective To comparatively analyze the immunological characteristics of patients with mild and severe influenza A (H1N1), and to provide the evidence for condition monitoring and treatment . Methods 52 cases with mild influenza A ( H1N1), 152 cases with severe influenza A ( H1N1) and 26 healthy subjects from July 1, 2009 to December 31, 2009 were enrolled in the study.Lymphocyte subsets in peripheral blood were analyzed by flow cytometry and the serum concentrations of interferon -γ( IFN-γ) and interleukin-4 (IL-4) were detected by enzyme-linked immune-sorbent assay (ELISA).Results The total lymphocyte counts were decreased obviously in patients with severe influenza A ( H1N1) than in mild pa-tients and in healthy subjects (P<0.01).The T lymphocyte, NK cells, CD4+T lymphocyte and CD8+T lym-phocyte were also decreased obviously in severe patients than in mild patients (P<0.01).The B lymphocyte and CD4+/CD8+were also decreased in severe patients than in mild patients but had no significant statistical difference (P=0.11, 0.175).The serum IFN-γlevels in patients with mild and severe influenza A (H1N1) were lower than those in control group, especially in patients with severe influenza A (H1N1) (compared with control group and mild group , P<0.01).And the changes of serum IL-4 levels were the same with the former, but there were no statistically significant differences in three groups (P>0.05).Con-clusion Immune dysfunction in patients with influenza A (H1N1) infection is associated with the severity of disease, especially cellular immunity .Therefore, monitoring of the immune system is valuable for the diag-nosis of influenza A(H1N1) infection.

Objective? To descriptively analyze the dynamic changes of chemotherapy-induced nausea and vomiting in patients of newly diagnosed with non-small cell lung cancer (NSCLC) during the first chemotherapy cycle after first chemotherapy with gemcitabine plus cisplatin (GP), in order to provide targeted prevention and nursing during the peak period. Methods? A total of 165 NSCLC patients from Shanghai Pulmonary Hospital from January to December 2017 were recruited by convenience sampling method. Chemotherapy-induced nausea and vomiting (CINV) were followed up on the 3rd, 5th, 7th, 14th, and 21st day of chemotherapy, and CINV grades were recorded. Results? In the first chemotherapy cycle, the incidence of nausea was 90.3% (149/165), mostly in grade 2, and the peak period was the 3rd to the 7th day after chemotherapy, while the incidence of vomiting was 50.9% (84/165), mostly in grade 1, and the peak period was the 4th to the 6th days. Conclusions? During the first chemotherapy cycle of GP regimen in patients newly diagnosed with NSCLC, the peak period of CINV was the 3rd to the 7th day, and lasted 3 to 5 days. According to the time window and duration of high incidence of nausea and vomiting, medical staff can intervene in a timely manner to prevent or reduce the occurrence of nausea and vomiting.

Colorectal cancer is one of the most common malignant tumors of the digestive system. The incidence of colorectal cancer in China is increasing year by year. Screening for adenomas, precancerous lesions and early cancers can effectively reduce the incidence and mortality of colorectal cancer. Therefore, colorectal cancer screening is particularly important. At present, the colorectal cancer examination is mainly divided into fecal examination and colon structural examination. The fecal examination includes fecal occult blood test, fecal exfoliated cell test and fecal genetic analysis. The colon structural examination includes barium enema, colonoscopy and computed tomography colonography. Colonoscopy is considered as the gold standard for the diagnosis of colorectal cancer. It has the advantage of high accuracy, and can be used to find precancerous lesions and remove them at the same time. However, the screening should be greatly restricted because of its invasive examination, the need for intestinal preparation, obvious discomfort and the high cost of medical treatment. Comparatively, fecal occult blood test is simple, easy, non-invasive, saving manpower and material resources, and is suitable for large population screening. Some scholars in China have begun to pay attention to colorectal cancer screening, and fecal occult blood test is widely used in these screenings.

The UL49.5 gene of most herpesviruses is conserved and encodes glycoprotein N. However, the UL49.5 protein of duck enteritis virus (DEV) (pUL49.5) has not been reported. In the current study, the DEV pUL49.5 gene was first subjected to molecular characterization. To verify the predicted intracellular localization of gene expression, the recombinant plasmid pEGFP-C1/pUL49.5 was constructed and used to transfect duck embryo fibroblasts. Next, the recombinant plasmid pDsRed1-N1/glycoprotein M (gM) was produced and used for co-transfection with the pEGFP-C1/pUL49.5 plasmid to determine whether DEV pUL49.5 and gM (a conserved protein in herpesviruses) colocalize. DEV pUL49.5 was thought to be an envelope glycoprotein with a signal peptide and two transmembrane domains. This protein was also predicted to localize in the cytoplasm and endoplasmic reticulum with a probability of 66.7%. Images taken by a fluorescence microscope at different time points revealed that the DEV pUL49.5 and gM proteins were both expressed in the cytoplasm. Overlap of the two different fluorescence signals appeared 12 h after transfection and continued to persist until the end of the experiment. These data indicate a possible interaction between DEV pUL49.5 and gM.
Animals ; Ducks/virology ; Genes, Viral/genetics ; Mardivirus/*genetics ; Membrane Glycoproteins/*genetics ; Microscopy, Fluorescence ; Phylogeny ; Polymerase Chain Reaction/veterinary ; Viral Envelope Proteins/*genetics

Objective:To investigate the clinicopathological features of pulmonary epithelioid hemangioendothelioma (PEHE).Methods:Eighteen cases of PEHE were collected from August 2011 to December 2018 at the First Affiliated Hospital of Zhengzhou University. All cases were retrospectively studied by hematoxylin and eosin staining and immunohistochemistry (IHC). The clinicopathological features were reviewed; the status of CAMTA1 and TFE3 gene was analyzed and patients′ outcome was followed up.Results:Of the 18 cases, there were 11 males and 7 females with a male to female ratio of 1.6 to 1.0. The patients′ age ranged from 36 to 68 years (mean 52 years). Twelve cases (12/18) showed a single nodule and six cases (6/18) showed multiple bilateral nodules. Seven cases (7/18) involved other organs besides lung. Seventeen (17/18) patients presented with respiratory symptoms and one patient (1/18) presented with abdominal pain. Grossly, the tumors were greyish-white nodules with indistinct borders. Microscopically the tumor cells were epithelioid and arranged in strands and nests, and cytoplasmic vacuoles were commonly noted. The stroma was myxochondroid or hyaline. By IHC, the tumor cells were positive for CD31(18/18), CD34 (16/18), ERG (18/18) and Fli-1 (18/18); CKpan was focally positive in 5 cases (5/18). TFE3 was positive in 3 cases (3/18), and Ki-67 index ranged from 5% to 30%. FISH analysis showed seventeen cases (17/18) had CAMAT1 rearrangement, one case had TFE3 rearrangement displaying a split signal. Eight patients (8/18) had surgical excision, three patients (3/18) had surgery and chemotherapy, and seven patients (7/18) had chemotherapy only. Four patients (4/18) died of the disease.Conclusions:Patients with PEHE have non-specific symptoms, and correct diagnosis depends on pathologic biopsy and the exclusion of other tumors with epithelioid morphology. Some patients with PEHE have poor prognosis, particularly in those who have multiple nodules, peripheral invasion or metastasis.

Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

Objective:To investigate the distribution characteristics and related factors of HBsAb in infants born to women with chronic hepatitis B virus (HBV) infection.Methods:A total of 605 infants born to women with chronic HBV infection who met the requirements for inclusion were selected as the subjects. Information about the mother′s previous HBV infection, biochemical indicators during pregnancy, pregnancy complications, information about delivery, and hepatitis B test result after birth were collected. HBsAg and HBsAb at the age of 1 year were determined, and HBsAg and HBsAb at the age of 7 months were retrospectively collected. The factors influencing HBsAb in infants were analyzed by ordered logistic regression.Results:In 605 infants, the infection rate was about 1%. Among them, 6 infants were positive for HBsAg and HBV DNA at 7 months and 1 year of age. Uninfected infants were divided into groups according to HBsAb titers. The result showed that there were significant differences in prothrombin activity (PTA) ( χ2=11.17, P=0.01), positive rate of HBeAg ( χ2=7.87, P=0.049) and HBsAg positive rate at birth ( χ2=10.52, P=0.02) among different groups. Multivariate ordered Logistic regression analysis showed that HBsAg negative at birth was an independent protective factor for HBsAb at 7 months of age ( OR=1.564, 95% CI 1.092-2.239, P=0.015). Logistic regression analysis of HBsAb at 1 year of age showed maternal gestational diabetes mellitus ( OR=1.578, 95% CI 1.126-2.210, P=0.008), infant enhanced immunization ( OR=81.207, 95% CI 31.202-211.352, P < 0.001) and antibody level at 7 months of age ( OR=42.123, 95% CI 22.824-77.739, P < 0.001) were independently associated with HBsAb at 1 year of age. Conclusions:HBsAg negative in venous blood at birth was an independent protective factor for HBsAb at 7 months of age, and enhanced immunization was an independent protective factor for HBsAb at 1 year of age.

OBJECTIVE: To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Carcinoma, Renal Cell/diagnosis* ; Retrospective Studies ; Kidney ; Carcinoma ; Kidney Neoplasms/diagnosis*