Intra-abdominal fat volume estimation by multi-detector rows computed tomography: relevance in surgical fellowship training program in Shanghai: a retrospective study

Background Intra-abdominal fat volume (IFV) has been shown to have a negative impact on surgical outcomes in gastric cancer (GC) and other gastrointestinal surgeries. The purpose of this study is to look into the relationship between IFV and perioperative outcomes in GC patients using multi-detector rows computed tomography (MDCT) and assess the importance of implementing this observation in current surgical fellowship training programs. Methods Patients with GC who underwent open D2 gastrectomy between May 2015 and September 2017 were included in the study. Based on MDCT estimation, patients were divided into high IFV (IFV ≥ 3,000 ml) and low IFV (IFV < 3,000 ml) groups. Perioperative outcomes for cancer staging, type of gastrectomy, intraoperative blood loss (IBL), anastomotic leakage, and hospital stay were compared between the two groups. This study was registered as CTR2200059886. Results Out of 226 patients, 54 had early gastric carcinoma (EGC), while 172 had advanced gastric carcinoma (AGC). There were 64 patients in the high IFV group and 162 in the low IFV group. The high IFV group had significantly higher IBL mean values (p = 0.008). Therefore, having a high IFV was a risk factor for the occurrence of perioperative complications (p = 0.008). Conclusions High IFV estimated by MDCT prior to GC surgery was associated with increased IBL and postoperative complications. Incorporating this CT-IFV estimation into surgical fellowship programs may aid aspiring surgeons in selecting patients during independent practice in their learning curve and surgical practice for the most appropriate approach for treating GC patients

Pollutants Source Assessment and Load Calculation in Baiyangdian Lake Using Multi-Model Statistical Analysis

Baiyangdian lake, the largest fresh lake on the Haihe Basin in North China, has attracted wide attention on account of the distinguished ecological water bodies in Xiong&rsquo;an New Area. Although remarkable achievements have been made in pollution control in Baiyangdian lake, the problem facing the overall water environment remains serious. The complex pollutant sources, drastic pollutant flux changes, and the unclear impact of the role of pollutants pose great challenges to the water quality, water environment management, and long-term restoration of the ecological environment. Here, the potential pollution sources, their contribution ratio, and the influence of the pollution load of different sources on the water quality in the priority source areas of Baiyangdian lake are discussed in detail based on collected and existing monitoring data. It is proven that the primary pollution sources of for nitrogen, phosphorus, and organic pollutants are from agricultural and rural non-point source pollution; the load contribution rates exceed 50%, of which the contribution rate to the total phosphorus load reaches 73.37%. The total load contribution of runoff to the three pollutants was small, although the contribution of soil erosion to total nitrogen was 22.95%. The contribution of point source pollution to COD was high, with a rate of 22.33%. In order to ensure the environmental quality of Baiyangdian lake, it is obligatory to strengthen the control of agricultural and rural pollution discharge and to standardize the pollution discharge of livestock and poultry breeding. This study provides a helpful support for protecting the water ecology of the national Xiong&rsquo;an New Area

Progress and challenges in the clinical evaluation of immune responses to respiratory mucosal vaccines

ABSTRACTIntroduction Following the coronavirus disease pandemic, respiratory mucosal vaccines that elicit both mucosal and systemic immune responses have garnered increasing attention. However, human physiological characteristics pose significant challenges in the evaluation of mucosal immunity, which directly impedes the development and application of respiratory mucosal vaccines.Areas Covered This study summarizes the characteristics of immune responses in the respiratory mucosa and reviews the current status and challenges in evaluating immune response to respiratory mucosal vaccines.Expert Opinion Secretory Immunoglobulin A (S-IgA) is a major effector molecule at mucosal sites and a commonly used indicator for evaluating respiratory mucosal vaccines. However, the unique physiological structure of the respiratory tract pose significant challenges for the clinical collection and detection of S-IgA. Therefore, it is imperative to develop a sampling method with high collection efficiency and acceptance, a sensitive detection method, reference materials for mucosal antibodies, and to establish a threshold for S-IgA that correlates with clinical protection. Sample collection is even more challenging when evaluating mucosal cell immunity. Therefore, a mucosal cell sampling method with high operability and high tolerance should be established. Targets of the circulatory system capable of reflecting mucosal cellular immunity should also be explored

Mixed formulation of mRNA and protein‐based COVID‐19 vaccines triggered superior neutralizing antibody responses

Abstract Integrating different types of vaccines into a singular immunization regimen is an effective and accessible approach to strengthen and broaden the immunogenicity of existing coronavirus disease 2019 (COVID‐19) vaccine candidates. To optimize the immunization strategy of the novel mRNA‐based vaccine and recombinant protein subunit vaccine that attracted much attention in COVID‐19 vaccine development, we evaluated the immunogenicity of different combined regimens with the mRNA vaccine (RNA‐RBD) and protein subunit vaccine (PS‐RBD) in mice. Compared with homologous immunization of RNA‐RBD or PS‐RBD, heterologous prime‐boost strategies for mRNA and protein subunit vaccines failed to simultaneously enhance neutralizing antibody (NAb) and Th1 cellular response in this study, showing modestly higher serum neutralizing activity and antibody‐dependent cell‐mediated cytotoxicity for “PS‐RBD prime, RNA‐RBD boost” and robust Th1 type cellular response for “RNA‐RBD prime, PS‐RBD boost”. Interestingly, immunizing the mice with the mixed formulation of the two aforementioned vaccines in various proportions further significantly enhanced the NAb responses against ancestral, Delta, and Omicron strains and manifested increased Th1‐type responses, suggesting that a mixed formulation of mRNA and protein vaccines might be a more prospective vaccination strategy. This study provides basic research data on the combined vaccination strategies of mRNA and protein‐based COVID‐19 vaccines

A Novel Single-Stranded RNA-Based Adjuvant Improves the Immunogenicity of the SARS-CoV-2 Recombinant Protein Vaccine

The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype genome. L2 could initiate retinoic acid-inducible gene-I signaling pathways to effectively activate the innate immunity. ZF2001, an aluminum hydroxide (Al) adjuvanted SARS-CoV-2 recombinant receptor binding domain (RBD) subunit vaccine with emergency use authorization in China, was used for comparison. L2, with adjuvant compatibility with RBD, elevated the antibody response to a level more than that achieved with Al, CpG 7909, or poly(I:C) as adjuvants in mice. L2 plus Al with composite adjuvant compatibility with RBD markedly improved the immunogenicity of ZF2001; in particular, neutralizing antibody titers increased by about 44-fold for Omicron, and the combination also induced higher levels of antibodies than CpG 7909/poly(I:C) plus Al in mice. Moreover, L2 and L2 plus Al effectively improved the Th1 immune response, rather than the Th2 immune response. Taken together, L2, used as an adjuvant, enhanced the immune response of the SARS-CoV-2 recombinant RBD protein vaccine in mice. These findings should provide a basis for the R&D of novel RNA-based adjuvants

Heterologous Omicron-adapted vaccine as a secondary booster promotes neutralizing antibodies against Omicron and its sub-lineages in mice

ABSTRACTOver one billion people have received 2–3 dosages of an inactivated COVID-19 vaccine for basic immunization. Whether a booster dose should be delivered to protect against the Omicron variant and its sub-lineages, remains controversial. Here, we tested different vaccine platforms targeting the ancestral or Omicron strain as a secondary booster of the ancestral inactivated vaccine in mice. We found that the Omicron-adapted inactivated viral vaccine promoted a neutralizing antibody response against Omicron in mice. Furthermore, heterologous immunization with COVID-19 vaccines based on different platforms remarkably elevated the levels of cross- neutralizing antibody against Omicron and its sub-lineages. Omicron-adapted vaccines based on heterologous platforms should be prioritized in future vaccination strategies to control COVID-19

Non-small cell lung cancers (NSCLCs) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors

Abstract With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy. Human enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses. In this study, coxsackievirus B5/Faulkner (CV-B5/F) was screened for its potential oncolytic effect against non-small cell lung cancers (NSCLCs) through inducing apoptosis and autophagy. For refractory NSCLCs, DNA-dependent protein kinase (DNA-PK) or ataxia telangiectasia mutated protein (ATM) inhibitors can synergize with CV-B5/F to promote refractory cell death. Here, we showed that viral infection triggered endoplasmic reticulum (ER) stress-related pro-apoptosis and autophagy signals, whereas repair for double-stranded DNA breaks (DSBs) contributed to cell survival which can be antagonized by inhibitor-induced cell death, manifesting exacerbated DSBs, apoptosis, and autophagy. Mechanistically, PERK pathway was activated by the combination of CV-B5/F and inhibitor, and the irreversible ER stress-induced exacerbated cell death. Furthermore, the degradation of activated STING by ERphagy promoted viral replication. Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred. Conclusively, our study identifies an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a potential therapy for NSCLCs

Development and Evaluation of a Pseudovirus-Luciferase Assay for Rapid and Quantitative Detection of Neutralizing Antibodies against Enterovirus 71

<div><p>The level of neutralizing antibodies (NtAb) induced by vaccine inoculation is an important endpoint to evaluate the efficacy of EV71 vaccine. In order to evaluate the efficacy of EV71 vaccine, here, we reported the development of a novel pseudovirus system expression firefly luciferase (PVLA) for the quantitative measurement of NtAb. We first evaluated and validated the sensitivity and specificity of the PVLA method. A total of 326 serum samples from an epidemiological survey and 144 serum specimens from 3 clinical trials of EV71 vaccines were used, and the level of each specimen's neutralizing antibodies (NtAb) was measured in parallel using both the conventional CPE-based and PVLA-based assay. Against the standard neutralization assay based on the inhibition of the cytopathic effect (CPE), the sensitivity and specificity of the PVLA method are 98% and 96%, respectively. Then, we tested the potential interference of NtAb against hepatitis A virus, Polio-I, Polio-II, and Polio-III standard antisera (WHO) and goat anti-G10/CA16 serum, the PVLA based assay showed no cross-reactivity with NtAb against other specific sera. Importantly, unlike CPE based method, no live replication-competent EV71 is used during the measurement. Taken together, PVLA is a rapid and specific assay with higher sensitivity and accuracy. It could serve as a valuable tool in assessing the efficacy of EV71 vaccines in clinical trials and disease surveillance in epidemiology studies.</p></div

Optimization of assay parameters.

<p>(<b>A</b>) <b>Determination of RD cell density.</b> RD cells (5×10⁴ cells per well) were incubated in a 96-well plate for 12 h with various dilutions of pseudovirus (from 2×10³ to 2×10⁷ copies per well) in a final volume of 200 μl per well. The data showed that the RLUs decreased with pseudotype in a dose dependent manner. The variation coefficient was lower than 5% for 5×10⁴ and 1×10⁵ cells per well at all the doses of pseudovirus. However, when the RD cell density was 2×10⁴ cells per well, the variation coefficient of RLU was higher than 15% with lower pseudovirus dosage. So the 5×10⁴ cells per well was chosen as the optimized RD cell density. (<b>B</b>) <b>Evaluation of luciferase activity at various incubation times.</b> RD cells (5×10⁴ cells per well) were incubated with 10⁶ copies pseudovirus per well in a 96-well plate for various time points, from 0.5 to 24 h, and each luciferase reading shown is the average of eight replicates. The results indicated that luciferase activity increased gradually with the extension of the incubation over time and reached a plateau at 12 h after incubation. therefore, 12 h was chosen as the optimized incubation time. (<b>C</b>) <b>Infection curve of EV71(FY)-Luc.</b> RD cells were incubated at 35°C together with a range of EV71 pseudovirus concentrations in a final volume of 200 μl per well in 96-well plates. Luciferase activity was measured 12 h post-infection. Each data point represents the average of eight replicates. Linear regression analysis was conducted using Graph Pad Prism. The results showed that when the dose of pseudovirus were within the range of 1×10⁴–10⁷ copies per well, there was a strong correlation between the viral dose and luciferase activity.</p