A First-in-Human Trial to Evaluate the Safety and Immunogenicity of a G Protein-Based Recombinant Respiratory Syncytial Virus Vaccine in Healthy Adults 18-45 Years of Age.

BACKGROUND: With the enormous morbidity and mortality caused by respiratory syncytial virus (RSV) infections among infants and the elderly, vaccines against RSV infections are in large market demand. METHODS: We conducted a first-in-human (FIH), randomized, double-blind, placebo-controlled dose escalation study to evaluate the safety and immunogenicity response of the rRSV vaccine (BARS13) in healthy adults aged 18-45. A total of 60 eligible participants were randomly assigned to receive one of four dose levels or vaccination regimens of BARS13 or placebo at a 4:1 ratio. RESULTS: The mean age was 27.40, and 23.3% (14/60) were men. No treatment-emergent adverse events (TEAEs) led to study withdrawal within 30 days after each vaccination. No serious adverse event (SAE) was reported. Most of the treatment-emergent adverse events (TEAEs) recorded were classified as mild. The high-dose repeat group had a serum-specific antibody GMC of 885.74 IU/mL (95% CI: 406.25-1931.17) 30 days after the first dose and 1482.12 IU/mL (706.56-3108.99) 30 days after the second dose, both higher than the GMC in the low-dose repeat group (885.74 IU/mL [406.25-1931.17] and 1187.10 IU/ mL [610.01-2310.13]). CONCLUSIONS: BARS13 had a generally good safety and tolerability profile, and no significant difference in terms of adverse reaction severity or frequency was observed between different dose groups. The immune response in repeat-dose recipients shows more potential in further study and has guiding significance for the dose selection of subsequent studies.

Impact of an emergency department nursing intervention on continuity of care, self-care, and psychological symptoms.

BACKGROUND: The emergency department plays a crucial role in providing acute care to patients. Nursing interventions in this setting are essential for improving the continuity of care, enhancing patients' self-care abilities, and reducing psychological symp-toms. AIM: To evaluate the effect of nursing interventions in the emergency department on these indicators in an emergency department. METHODS: A retrospective analysis was conducted on 120 patients admitted to the emergency department between January 2022 and May 2023. The patients were divided into two groups: The control group (conventional nursing intervention) and the observation group (conventional nursing intervention + emergency department nursing intervention). The two groups were compared regarding continuity of care, self-care ability, psychological symptoms, and satisfaction with care. RESULTS: The emergency department nursing interventions significantly improved the continuity of care, enhanced patients' self-care abilities, and reduced psychological symptoms such as anxiety and depression. CONCLUSION: Nursing interventions in the emergency department positively impact continuity of care, self-care, and psychological symptoms. However, it is important to acknowledge the limitations of this study, including the small number of studies, variable methodological quality, and the heterogeneity of the study population. Future research should address these limitations and further explore the effects of different types of nursing interventions in the emergency department. Additionally, efforts should be made to enhance the application and evaluation of these interventions in clinical practice.

Medical Information Mining-Based Visual Artificial Intelligence Emergency Nursing Management System.

This study aims to design a set of the visual artificial intelligence system based on medical information mining for hospital emergency care management. A visual artificial intelligence emergency first aid nursing management system is designed by analyzing the needs of the emergency first aid nursing management system. The results show that system personnel allocation, comparative management, record management, query management analysis, basic setup analysis, nursing management basis, and nonfunctional requirements all need to be optimized for the emergency first aid management system. In this study, the comparative management module, log management module, and the query management module are designed, and the emergency first aid management system of different APP terminal functions in different modules is described in detail. The nursing document query business is tested, and the corresponding time of query of nursing assessment sheet, nurse shift record, nurse record, and physical sign observation sheet is 375.50 ms, 351.48 ms, 336.36 ms, and 245.57 ms, respectively. It shows that the visual artificial intelligence emergency nursing management system based on medical information mining can provide convenience for clinical work to a large extent and has potential application value in hospital emergency nursing work.

The effect of emergency nursing on the mental health and limb function recovery of myocardial infarction patients.

OBJECTIVE: To evaluate the effect of emergency care on the mental health and recovery of limb function in myocardial infarction (MI) patients. METHODS: We recruited 106 MI patients consecutively admitted to the emergency center of our hospital from June, 2016 to January, 2019. Among them, 51 underwent routine care (the control group) and 55 underwent emergency care (the observation group). The rescue success rates, the pre-hospital times, the emergency rescue times, and the door-to-balloon times were recorded and compared. The patients' heart rates, respiratory frequencies, and blood pressure levels were monitored after the care. The self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were used to evaluate the patients' psychological states. The patients' limb function and activities of daily living (ADL) were evaluated using the Fugl-Meyer assessment (FMA) and the modified Barthel index (MBI), respectively. The incidences of complications were compared between the two groups. The Short-Form 36 Item Health Survey (SF-36) was used to evaluate the patients' quality of life (QOL), and a self-made satisfaction questionnaire was developed to evaluate the patient satisfaction. RESULTS: After the emergency care, there was a higher rescue success rate and shorter pre-hospital times, emergency rescue times, and door-to-balloon times in the observation group. The heart rates, respiratory frequencies, and blood pressure levels in the observation group were more stable than they were in the control group. The patients in the observation group had lower SAS and SDS scores (P<0.05), lower FMA and lower MBI (P<0.05), as well as a lower incidence of complications (P<0.05). The QOL was greatly improved in the observation group after two weeks of care. The patients in the observation group were more satisfied with the nursing service than the patients in the control group (P<0.05). CONCLUSION: Emergency care contributes to the improvement of mental health and limb function, as well as MI patient prognosis, so it is well worthy of promoting.

On the Cryptanalysis of a Latin Cubes-Based Image Cryptosystem.

Based on orthogonal Latin cubes, an image cryptosystem with confusion-diffusion-confusion cipher architecture has been proposed recently (Inf. Sci.2019, 478, 1-14). However, we find that there are four fatal vulnerabilities in this image cryptosystem, which leave open doors for cryptanalysis. In this paper, we propose a reference-validation inference algorithm and design screening-based rules to efficiently break the image cryptosystem. Compared with an existing cryptanalysis algorithm, the proposed method requires fewer pairs of chosen plain-cipher images, and behaves stably since different keys, positions of chosen bits and contents of plain images will not affect the cryptanalysis performance. Experimental results show that our cryptanalysis algorithm only requirespairs of chosen plain-cipher images, whererepresents the image's resolution. Comparative studies demonstrate effectiveness and superiority of the proposed cryptanalysis algorithm.

Neonatal priming and infancy boosting with a novel respiratory syncytial virus vaccine induces protective immune responses without concomitant respiratory disease upon RSV challenge.

Although respiratory syncytial virus (RSV) infection in infants and young children is a global public health issue, development of a safe RSV vaccine has been impeded by formalin-inactivated RSV-enhanced respiratory disease (ERD). In developing a safer yet effective RSV vaccine for children, a strategy to decrease over-reactive T cells and increase neutralizing anti-RSV antibodies should be considered. We previously demonstrated that adult mice immunized with RSV recombinant G protein plus low-dose Cyclosporine A (G+ CsA) could, upon subsequent RSV challenge, produce increased levels of antigen-specific T regulatory cells in lungs that overcame the ERD. Neutralizing anti-RSV antibodies that prevented viral infection were also elicited. In this study, we investigated if such a G+ CsA vaccine could provide infant mice with the same protection from RSV infection without ERD. The results showed that the G+ CsA vaccine could prevent RSV infection with only a mild loss of body weight. Importantly, there was nearly normal morphology and no mucus appearance in lung tissues after RSV challenge. These results demonstrate that the G+ CsA vaccine strategy achieved similar benefits in the neonatal prime and infancy boost model as in the adult mouse model. The G+ CsA immunization strategy is potentially safe and effective in neonates and infants because it suppresses the devastating ERD.

Ursolic acid benzaldehyde chalcone, leads to inhibition of cell proliferation and arrests cycle in G1/G0 phase in colon cancer.

The present study investigates the effect of matrine on colon cancer cell viability and apoptosis and tumor growth in mice xenograft model. The results from MTT assay revealed a concentration and time dependent reduction in viability of HCT8 and HT29 colon cancer cells by matrine. The viability of HCT8 and HT29 cells was reduced to 24.67 and 29.32% on treatment with 4 µM/ml concentration of matrine after 48 h (P < 0.05). The results from flow cytometry revealed increase in population of HCT8 and HT29 cells to 77.6 ± 0.3 and 54.0 ± 5.4%, respectively compared to 1.4 ± 0.3 and 2.4 ± 0.7% in control on exposure to 1 µM/ml concentration of matrine. Histone H2AX phosphorylation and expression of Myt1, cyclin A2, cyclin B1 and p53 were increased in HCT8 and HT29 cells on treatment with matrine for 48 h. Matrine treatment also increased the phosphorylation of cdc2 significantly compared to control cells at 48 h (P < 0.05). Results from Annexin-V/FITC-staining showed increase in proportion of apoptotic cells in HCT8 and HT29 cells 67.52 and 68.56 on treatment with 1 µM/ml of matrine. Matrine treatment caused a marked reduction in the growth of HCT8 cell xenograft after 21 days. Thus matrine inhibits cell viability, induces apoptosis and inhibits tumor growth in colon cancer.

Crocetin treatment inhibits proliferation of colon cancer cells through down-regulation of genes involved in the inflammation.

BACKGROUND: The current study was designed to investigate the effect of crocetin on the proliferation inhibition of colon cancer cells and the underlying mechanism. METHODS: MTT assay showed inhibition of proliferation of colon cancer cells in a dose based manner by crocetin treatment. At 30 µM concentration of crocetin proliferation rate of colon cancer cells was reduced to 14% after 24 h. Flow cytometry and fluorescence microscopy revealed induction of apoptosis in colon cancer cells on treatment with crocetin. The tube formation was suppressed significantly in the cultures of HUVEC treated with 30 µM concentration of crocetin compared to the control cultures. RESULTS: The results from transwell assay revealed a significant reduction in the population of DU-145 cells passing through filters of transwell on treatment with crocetin compared to the control cells. Treatment of the DU-145 cells with crocetin caused a significant reduction in the expression levels of NF-κB, VEGF and MMP-9. The results from RT-PCR analysis revealed a significant reduction in the expression of genes involved in inflammation including, HMGB1, IL-6 and IL-8 on treatment of DU-145 cells with crocetin. However, the expression of NAG-1 gene was increased by crocetin treatment in DU-145 cells significantly compared to the control cells. CONCLUSION: Crocetin inhibits growth of colon cancer cells and prevents tube formation through induction of apoptosis. Therefore, crocetin can be used efficiently for the treatment of colon cancer.

Serum Salusin-ß Levels Are Correlated with Slow Coronary Flow.

CONTEXT: Slow coronary flow (SCF) is a special coronary microvascular disorder associated with recurrent chest pain. The pathogenesis of SCF remain unclear. OBJECTIVES: We sought to assess whether serum salusin-ß levels are correlated with SCF. METHODS: We enrolled 76 patients with angiographically confirmed SCF and 108 age- and gender-matched controls. We measured serum salusin-ß levels by enzyme-linked immunosorbent assay and coronary flow rate was assessed using thrombolysis in myocardial infarction frame count (TFC). RESULTS: Serum salusin-ß levels were elevated in SCF patients compared with controls (4.33 [range 3.52-5.87] nmol/L vs. 3.76 [range 2.98-4.67] nmol/L). Multivariate logistic regression analysis revealed that salusin-ß in serum was the independent predictor of SCF (odds ratio = 1.814). Serum salusin-ß levels were independently correlated with mean-TFC (r = 0.355, p = 0.002). CONCLUSIONS: Serum salusin-ß levels were independently associated with SCF. Therefore, our findings implicate a potential role of salusin-ß in the pathophysiology of SCF and provide insights on both risk stratification and modification in this patient population.

A Recombinant G Protein Plus Cyclosporine A-Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease.

Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.

Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells (DCs) could be induced under different conditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus (HBV) therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with recombinant HBV vaccine (rHBVvac) in mice. We observed greater DC maturation in these pre-treated animals at day 3 as compared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic (HBsAg-Tg) animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-γ production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8+ T cells from immunized animals, antigen-specific CD8+ T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination could significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protocol utilizing GM-CSF as an adjuvant in combination with the rHBVvac vaccine has the potential to become a novel immunotherapy for chronic hepatitis B patients.

Day surgery versus overnight stay laparoscopic cholecystectomy: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic cholecystectomies are being increasingly performed as a day surgery procedure. AIM: To systematically assess the safety and efficacy of laparoscopic cholecystectomy as a day surgery procedure compared to overnight stay. METHODS: Randomized controlled trials and clinical controlled trials involving day surgery laparoscopic cholecystectomy were included in a systematic literature search. Two authors independently assessed the studies for inclusion and extracted the data. A meta-analysis was conducted to estimate the safety and feasibility of day surgery compared to overnight stay laparoscopic cholecystectomy. RESULTS: Twelve studies were selected for our meta-analysis. The meta-analysis showed that there was no significant difference between the two groups on morbidity (P=0.65). The mean in-hospital admission and readmission rates were 13.1% and 2.4% in the day surgery group, respectively. The two groups had similar prolonged hospitalization (P=0.27), readmission rate (P=0.58) and consultation rate (P=0.73). In addition, there was no significant difference in the visual analogue scale score, postoperative nausea and vomiting scale, time to return to activity and work between the two groups (P>0.05). CONCLUSIONS: Currently available evidence demonstrates that laparoscopic cholecystectomy can be performed safely in selected patients as a day surgery procedure, though further studies are needed.

Trivaric acid, a potent depside human leukocyte elastase inhibitor.

Human leukocyte elastase (HLE) is a serine protease implicated in several inflammatory diseases, and represents a major target for anti-inflammatory drug development. In the present study, nordivaricatic acid (1), divarinyl divarate (2), and trivaric acid (3), three depsides isolated from the culture of a soil derived fungal strain were identified as inhibitors of HLE. Two didepsides 1 and 2 showed low inhibitory activity. In contrast, trivaric acid, a para-tridepside, exhibited highly potent inhibitory activity with an IC(50) value of 1.8 µM and a K(i) of 0.6 µM. Kinetic investigations with trivaric acid showed that this inhibition is reversible, competitive pattern. Further studies on the selectivity of three depsides toward serine proteases showed that they did not inhibit chymotrypsin, trypsin and thrombin even at 150 µM.

[Coumarins of Anemone raddeana Regel and their biological activity].

To study the coumarins of Anemone raddeana Regel, the compounds were separated by silica gel column chromatography and HPLC. Their structures were identified by their physicochemical property and spectral analysis. Two new compounds were isolated and identified as 4, 7-dimethoxyl-5-methyl-6-hydroxy coumarin (1) and 4, 7-dimethoxyl-5-formyl-6-hydroxycoumarin (2). The bioassays indicated that compounds 1 and 2 could significantly inhibit the proliferation of cancer cell, and showed the agonist effect on the transactivity of retinoic acid receptor-alpha (RARalpha). In addition, the two compounds had inhibitory effect against human leukocyte elastase (HLE).

Health-related quality of life of liver transplant recipients: a single center experience.

BACKGROUND/AIMS: To evaluate the health related quality of life (HRQOL) of liver transplant recipients and to identify risk factors influencing post-operative HRQOL. METHODOLOGY: Adult patients who underwent primary liver transplantation from 2009 to 2010 were asked to complete a HRQOL survey at pre-operation and one year postoperatively. We compared the HRQOL of liver transplant recipients at pre-transplantation and one year postoperatively to the general population. Pre-transplant variables were analyzed to identify the risk factors influencing postoperative HRQOL. RESULTS: Pre-transplant HRQOL was significantly lower than that of the general population and significantly improved at one year postoperatively. Multivariate analyses suggested hepatocellular carcinoma, pre-transplant hypertension and high model for end-stage liver disease score were independent risk factors for postoperative physical component summary (PCS); and higher education level, marital status and lower income level negatively impacted on the postoperative mental component summary (MCS). CONCLUSIONS: Factors influencing postoperative HRQOL were identified in the present study. Transplant centers should pay more attention to patients with above-mentioned risk factors and strive to improve the HRQOL.

[Perioperative nursing of 50 recipients undergoing adult-to-adult living donor liver transplantation].

OBJECTIVE: To summarize the perioperative nursing experience for recipients undergoing adult-to-adult living donor liver transplantation(A-ALDLT). METHODS: 50 cases of recipients undergoing A-ALDLT in our hospital January 2002 to July 2006 were retrospectively analyzed for perioperative nursing. RESULTS: All the successful operations for A-ALDLT got without nursing complications. 1-year survival rate was 92%, which means the care effect was satisfactory. CONCLUSION: Perioperative nursing is one important factor of elements to guarantee the success of LDLT. The actively and effectively perioperative nursing measures are the important insurance to the recipients' recovery from graft operation.

Ion-exchange chromatography of hepatitis B virus surface antigen from a recombinant Chinese hamster ovary cell line.

About 10% of the Chinese population are chronic carriers of hepatitis B virus (HBV). Thus, the development of a highly efficient process for the preparation of a vaccine based on a recombinant hepatitis B surface antigen (HBsAg) is very important to the Chinese national immunization program. To this end, the ion exchange chromatography recovery of CHO-HBsAg from a recombinant Chinese hamster ovary cell line was shown to increase from about 55 to 80% by the addition of 1% poly(ethylene glycol) (PEG 10,000) to the mobile phase. Furthermore, based on analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the intact glycoprotein form of CHO-HBsAg was completely preserved by the addition of PEG. In the absence of PEG the glycoprotein form of CHO-HBsAg was also spread out into the high salt elution fraction. High-performance size-exclusion chromatography with on-line multiangle-laser-light scattering (HPSEC-MALLS) analysis was performed to monitor the status of the CHO-HBsAg aggregate structure assembly, particle size and molecular weight distribution after each purification step, and the results showed further that the presence of PEG facilitated the separation and recovery of intact glycoprotein form of CHO-HBsAg and promoted their assembly to proper virus-like particles, which are both important features and prerequisites of their immunogenicity.

[Polyethylene glycol-accompanied ion-exchange chromatography to purify recombinant hepatitis B virus surface antigen].

The dissociation of virus-like particles of Hepatitis B surface antigen (HBsAg) during the adsorption-desorption on the solid-phase of chromatography is a main challenge for its purification. Herein, poly (ethylene glycol) (PEG) was applied as an additive during the purification of HBsAg from recombinant Chinese hamster ovary (CHO) cell culture to improve the HBsAg recovery and protect its structural assembly. The presence of 1% of PEG10000 in the mobile phase of ion-exchange chromatography (IEC) of DEAE-Sepharose FF column could increase the recovery of HBsAg from about 55% to 80%, with a similar purification (-fold) (about 12) compared with the absence of PEG. Importantly, glycosylated protein forms of HBsAg were reserved well by PEG-accompanied chromatography. Furthermore, size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) analysis was performed on line to monitor the aggregates, particle size and molecular weight distribution of HBsAg. The results demonstrated that the HBsAg particle size and assembly are more homogenous after adding PEG in the mobile phase of IEC than no PEG added in the mobile phase.