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IntroductionHuman adenovirus type 7 (HAdv-7) infection is the main cause of upper respiratory tract infection, bronchitis and pneumonia in children. At present, there are no anti- adenovirus drugs or preventive vaccines in the market. Therefore, it is necessary to develop a safe and effective anti-adenovirus type 7 vaccine.MethodsIn this study, In this study, we used the baculovirus-insect cell expression system to design a recombinant subunit vaccine expressing adenovirus type 7 hexon protein (rBV-hexon) to induce high-level humoral and cellular immune responses. To evaluate the effectiveness of the vaccine, we first detected the expression of molecular markers on the surface of antigen presenting cells and the secretion of proinflammatory cytokines in vitro. We then measured the levels of neutralizing antibodies and T cell activation in vivo.ResultsThe results showed that the rBV-hexon recombinant subunit vaccine could promote DC maturation and improve its antigen uptake capability, including the TLR4/NF-κB pathway which upregulated the expression of MHCI, CD80, CD86 and cytokines. The vaccine also triggered a strong neutralizing antibody and cellular immune response, and activated T lymphocytes.DiscussionTherefore, the recombinant subunit vaccine rBV-hexon promoted promotes humoral and cellular immune responses, thereby has the potential to become a vaccine against HAdv-7.

Oncolytic virotherapy is emerging as an important modality in cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual cancer-selective anti-tumor recombinant adenovirus.To explore the therapeutic effect of recombinant adenovirus Ad-VT together with Etoposide on small cell lung cancer, the ability of Ad-VT alone, Etoposide alone, and a combination of Ad-VT + Etoposide to inhibit proliferation of NCI-H446 and BEAS-2B cells was investigated using the WST-1 method. According to the inhibitory action of different combinations, a combination index (CI) was estimated by CalcuSyn software to select the best combination. The inhibitory effect of Ad-VT combined with Etoposide on NCI-H446 and BEAS-2B cells was detected by crystal violet staining and the CFST method. Hoechst, Annexin V and JC-1 staining were used to explore the inhibitory pathway of Ad-VT combined with Etoposide on NCI-H446 cells. The migratory and invasive abilities of treated NCI-H446 cells were assessed by Transwell and BioCat methods. Tumor volume, body weight and survival rate were measured to analyze the anti-tumor and toxic effects of different treatments in tumor-bearing mice.Ad-VT (20 MOI) combined with Etoposide (400 nM) significantly inhibited NCI-H446 cell proliferation with reduced toxicity of Etoposide to normal cells. Ad-VT induced apoptosis of NCI-H446 cells mainly through the mitochondrial apoptosis pathway, an effect significantly increased by the combined treatment. Ad-VT together with Etoposide significantly inhibited migration and invasion of NCI-H446 cells, inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice.The above results indicate that when combined with Etoposide, Ad-VT may have an important role in synergistically inhibiting tumors.

Influenza viruses pose a serious threat to human health, infecting hundreds of millions of people worldwide each year, resulting in a significant increase in global morbidity and mortality. Influenza activity has declined at the onset of the COVID-19 pandemic, but the genetic diversity of B/Victoria lineage viruses has increased significantly during this period. Therefore, the prevention and treatment of the influenza B Victoria strain virus should continue to attract research attention. In this study, we found that Atractyloside A (AA), one of the effective components in Atractylodes lancea (Thunb.) DC shows potential antiviral properties. This study shows that AA not only possesses anti-influenza B virus infection effects in vivo and in vitro but also can regulate macrophage polarization to the M2 type, which can effectively attenuate the damage caused by influenza B virus infection. Therefore, Atractyloside A may be an effective natural drug against B/Victoria influenza infection.

Aims To determine the effectiveness and dose–response of nurse-led hospital-to-home transitional care interventions (TCIs) on patient mortality and psychosocial outcomes of health-related quality of life (HRQoL), self-care behaviours, and emotional well-being in adults hospitalized with heart failure (HF) and to recognize pertinent characteristics that potentially affect the overall effectiveness. Methods and results Relevant studies were identified through electronic database searches, including MEDLINE, Embase, CINAHL, and Cochrane Library from January 2000 until January 2021. Two independent authors performed study selection, data abstraction, and risk-of-bias assessment. When appropriate, we used random-effects meta-analysis to derive pooled effect estimates, investigated dose–response relationships, and ran meta-regressions to locate the source of heterogeneity. A total of 27 studies with 7635 participants were included. Our findings revealed that nurse-led hospital-to-home TCIs reduced the risk of all-cause mortality by 21% [risk ratio = 0.79; 95% confidence interval (CI) 0.68–0.92; P = 0.003] and improved HRQoL (mean difference = −3.29; 95% CI −6.51 to −0.07; P = 0.04) compared to usual care, but non-significant effects were found for emotional well-being. The narrative summary of evidence for self-care behaviours showed positive intervention effects. Meta-regression did not find any covariates that were significantly related to mortality or HRQoL. Dose–response analysis showed that mortality risk was reduced with increased intensity and complexity of the nurse-led TCIs. Conclusion Generally, nurse-led hospital-to-home TCIs may play a beneficial role in decreasing mortality, and improving HRQoL and self-care behaviours for adults with HF. Additional studies are warranted to characterize the optimal nurse-led TCIs for HF management.

Background Infection is one of the most common causes of death in patients with hematological malignancies during chemotherapy. Due to its special location, local warmth and humidity, repeated pollution with stool and urine, and characteristically wrinkled anatomical structure within which bacteria can hide, the perianal becomes a site with a high incidence of infection. Such infection also has a high recurrence rate and high mortality, increasing the economic burden of patients, delaying the time of treatment and reducing the quality of life. In severe cases, sepsis occurs and endangers the patient’s life. Previous studies have confirmed the effectiveness of povidone iodine (PI) in the prevention of perianal infection in patients with hematological malignancies during chemotherapy, but these reports have not documented in detail the adverse events associated with sitz bathing and the lack of randomized controlled trials of different concentrations of dilute povidone iodine sitz bathing. Therefore, the evidence is insufficient. Hence, the objective of this paper is to determine whether a povidone iodine diluent sitz bath can reduce the incidence of perianal infection compared with conventional perianal cleaning care and to observe the incidence of perianal infection, the severity of perianal infection, and the complications related to the sitz bath among groups treated with different concentrations of povidone iodine diluent, especially in high-risk patients prone to perianal infection, to screen for the optimal concentration. Methods The trial is designed as a single-center, parallel, randomized, controlled and intervention trial with four parallel groups, and a primary endpoint of perianal infection occurred after this hospitalization chemotherapy. Randomization will be performed as simple randomization with a 1:1:1:1 allocation. This study received full ethics committee approval. The first patient was enrolled on May 1, 2021. A total of 268 patients with hematological malignancies undergoing chemotherapy who have risk factors for perianal infection will be enrolled with informed consent and randomly allocated to one of the four arms receiving (1) perianal cleaning care (control group D), (2) 1:100 PI diluted sitz bath (intervention group A), (3) 1:200 PI diluted sitz bath (intervention group B), and (4) 1:300 PI diluted sitz bath (intervention group C). The primary endpoint of the trial was the incidence of perianal infection. The secondary endpoints of the study will be the results of anal swab bacterial culture, the severity of perianal infection, the incidence of perianal adverse events (dryness, peeling, pigmentation, burning sensation), and pain scores. The length of hospitalization in days and hospitalization expenses will be recorded. Safety will be assessed with consideration of all adverse and severe adverse events related to the study treatment. Discussion We hypothesized that patients with hematological malignancies during chemotherapy would benefit from a povidone iodine diluted sitz bath. This study will provide evidence-based recommendations for clinicians and nurses. Trial registration Chinese Clinical Trial Registry (registration ID: ChiCTR2000041073). Registered on December 17, 2020. The protocol version number is V1.0,20201217. http://www.chictr.org.cn/edit.aspx?pid=66044&htm=4

Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. Herein, we found that Apoptin induced a strong and lasting endoplasmic reticulum (ER) stress response, CaThe intracellular levels of calcium (CaThis study showed that Apoptin induced a strong and long- lasting ER stress and injury, which subsequently led to an imbalance of cellular CaIn summary, Apoptin induced apoptosis in HepG-2 cells via Ca

In this study, we compared the inhibitory effects of recombinant oncolytic adenovirus (Ad-apoptin-hTERTp-E1a, Ad-VT) with that of doxorubicin (DOX), a first-line chemotherapy drug, and tamoxifen (TAM), an endocrine therapy drug, on the proliferation of breast cancer cells. We found that Ad-VT could effectively inhibit the proliferation of breast cancer cells (p 0.01); the inhibition rate of Ad-VT on normal mammary epithelial MCF-10A cells was less than 20%. DOX can effectively inhibit the proliferation of breast cancer cells and also has a strong inhibitory effect on MCF-10A cells (p 0.01). TAM also has a strong inhibitory effect on breast cancer cells, among which the oestrogen-dependent MCF-7 cell inhibition was stronger (p 0.01), At higher concentrations, TAM also had a high rate of inhibition (70%) on the proliferation of MCF-10A cells. We also found that both recombinant adenovirus and both drugs could successfully induce tumour cell apoptosis. Further Western blot results showed that the recombinant adenovirus killed breast cancer cells through the endogenous apoptotic pathway. Analysis of the nude mouse subcutaneous breast cancer model showed that Ad-VT significantly inhibited tumour growth (the luminescence rate of cancer cells was reduced by more than 90%) and improved the survival rate of tumour-bearing mice (p 0.01). Compared with DOX and TAM, Ad-VT has a significant inhibitory effect on breast cancer cells, but almost no inhibitory effect on normal breast epithelial cells, and this inhibitory effect is mainly through the endogenous apoptotic pathway. These results indicate that Ad-VT has significant potential as a drug for the treatment of breast cancer.

Pyroptosis is related to the occurrence, development, and therapeutic response of tumors, mediated by the proteins of the Gasdermin family. These proteins have become potential biomarkers for cancer treatment, and their agonists are likely to become a new direction in research and development of antitumor drugs. In this study, we found that myricetin has an inhibitory effect on lung cancer cells of the activation of pyroptosis. Analysis of the expression of Gasdermin family proteins revealed that this phenomenon was caused by the cleavage of GSDME. Subsequently, specific inhibitors, we found that caspase-3 was its upstream activation factor. In addition, mitochondrial and endoplasmic reticulum (ER) analysis showed that myricetin can cause endoplasmic reticulum stress and increase reactive oxygen species (ROS) levels. Subsequent inhibition of caspase-12 revealed that the expression levels of cleaved-caspase-3 and cleaved-GSDME were significantly reduced, resulting in the inhibition of pyroptosis. Using

Objectives Heart failure (HF) heavily burdens the global health system. Transitional care interventions attempt to streamline the hospital-to-home transition to ease the burden. This systematic review and meta-analysis aimed to evaluate the effectiveness of transitional care interventions on health care utilization after hospitalization for HF. Design Systematic review and meta-analysis including dose-response relationship. Setting and Participants Randomized controlled trials (RCTs) of transitional care interventions vs usual care in older patients discharged from the hospital with HF. Methods Electronic databases including MEDLINE, Embase, Cochrane Library, and CINAHL, were systematically searched from January 2009 to October 2019 to locate relevant systematic reviews or meta-analyses. The original RCTs included in the review articles were identified, and an additional search for recently published RCTs was performed from January 2014 to June 2020. This systematic review focused on health care utilization outcomes, including hospital readmissions for HF or any cause, emergency department (ED) visits, and length of hospital stay (LOS). Results Data were summarized from 38 RCTs covering 10,871 patients. Pooled evidence suggested a mean 11% [risk ratio (RR) 0.89, 95% confidence interval (CI) 0.82, 0.97] and 22% (RR 0.78, 95% CI 0.68, 0.89) risk reduction on all-cause and HF-specific readmissions, but no significant reduction (RR 0.94, 95% CI 0.83, 1.07) on ED visits. Findings were mixed for LOS. Subgroup analysis by different types of transitional care interventions indicated that multidisciplinary interventions currently have the best evidence for reducing readmissions up to 6 months post the index HF hospitalization. In addition, we observed an inverse linear dose-response relationship between intervention intensity (ie, frequency and duration of interventions) and complexity (ie, number of intervention components) and the risk of HF readmissions. Conclusions and Implications Transitional care interventions for hospitalized patients with HF reduced all-cause and HF-specific readmissions, but did not decrease ED visits. Multidisciplinary interventions are highly recommended if adequate resources are available.

Abstract: Pyruvate kinase M2 (PKM2) is a key enzyme in aerobic glycolysis, and which plays an important role in tumor energy metabolism and tumor growth. Ad-apoptin, a recombinant oncolytic adenovirus, that can stably express apoptin in tumor cells and selectively causes cell death in tumor cells. The relationship between the anti-tumor function of apoptin, including apoptosis and autophagy activation, and energy metabolism of tumor cells has not been clarified. In this study, we used the A549 lung cancer cell line to analyze the mechanism of PKM2 involvement apoptin-mediated cell death in tumor cells. PKM2 expression in lung cancer cells was detected by Western blot and qRT-PCR. In the PKM2 knockdown and over-expression experiments, A549 lung cancer cells were treated with Ad-apoptin, and cell viability was determined by the CCK-8 assay and crystal violet staining. Glycolysis was investigated using glucose consumption and lactate production experiments. Moreover, the effects of Ad-apoptin on autophagy and apoptosis were analyzed by immunofluorescence using the Annexin v-mCherry staining and by western blot for c-PARP, p62 and LC3-II proteins. Immunoprecipitation analysis was used to investigate the interaction between apoptin and PKM2. In addition, following PKM2 knockdown and overexpression, the expression levels of p-AMPK, p-mTOR, p-ULK1, and p-4E-BP1 proteins in Ad-apoptin treated tumor cells, were analyzed by western blot to investigate the mechanism of apoptin effect on the energy metabolism of tumor cells. The in vivo antitumor mechanism of apoptin was analyzed by xenograft tumor inhibition experiment in nude mice and immunohistochemistry of tumors’ tissue. As a result, apoptin could target PKM2, inhibit glycolysis and cell proliferation in A549 cells, and promote autophagy and apoptosis in A549 cells by regulating the PKM2/AMPK/mTOR pathway. This study confirmed the necessary role of Ad-apoptin in energy metabolism of A549 cells.

Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. Herein, we found that Apoptin induced a strong and lasting endoplasmic reticulum (ER) stress response and Ca2+ imbalance, and triggered the mitochondrial apoptotic pathway. The aim of this study was to explore the mechanisms by which Apoptin exhibited anti-tumor effects on the HepG-2 cells. The intracellular level of calcium (Ca2+) was induced by ER stress and determined by electron microscopy, flow cytometry and fluorescence staining. Mitochondrial injury was determined by mitochondrial membrane potential, electron microscopy. Western blotting was used to investigate the levels of key proteins in the ER stress and the apoptotic pathway in the mitochondria. The relationship between Ca2+ level and apoptosis on Apoptin-treating cells was analyzed using Ca2+ chelator (BAPTA-AM), flow cytometry and fluorescence staining. We also investigated the in vivo effects of Ca2+ imbalance on the mitochondrial apoptotic pathway using the tumor tissues xenografted on nude mice. In vitro and in vivo experiments showed that Apoptin caused an imbalance in Ca2+, and increased the expression levels of Smac/Diablo and Cyto-C. In summary, Apoptin induced apoptosis in HepG-2 cells via Ca2+ imbalance-triggered mitochondrial apoptotic pathway. This study provided a new direction for antitumor research in Apoptin.

Two new sesquiterpenes, including 7-epi-3-eudesmene-1β,11-diol (1) and (7S,10R)-11-hydroxy-4,5-seco-guai-1-ene-4-one (2); one new natural product (11-hydroxy-1-oxo-4β,5β,7β,10β-eremophilane); (3) and nine known compounds were isolated from the aerial parts of Hyssopus cuspidatus Boriss. Their structures as well as their absolute configurations were elucidated by extensive spectroscopic analyses and quantum chemical calculations. Compounds 1 to 9 were tested to evaluate their inhibitory effects on NO production in LPS-induced RAW264.7 cells. Compounds 5 and 8 exhibited inhibitory effects, with IC50 values of 40.43 and 32.56 μM, respectively, compared to the positive control (i.e., dexamethasone, IC50 = 70.35 μM), and compound 4 exhibited a weaker activity, with an IC50 value of 112.56 μM.

Background: Apoptin, as a tumor-specific pro-apoptotic protein, apoptin plays an important role in the field of anti-tumor, but its autophagy activation mechanism and the interaction between autophagy and apoptosis have not been accurately elucidated. Here, we studied the mechanism of apoptosis and autophagy induced by apoptin and the interaction between autophagy and apoptosis. Methods: Through crystal violet staining and CCK-8 assay, we analyzed the effect of apoptin in inhibiting liver cancer in vitro, and also analyzed the effect of inhibiting liver cancer in vivo by establishing a nude mouse tumor model. Flow cytometry and fluorescence staining were used to analyze the main types of apoptosis and autophagy induced by apoptin. Subsequently, the relationship between apoptosis and autophagy induced by apoptin was analyzed. Then, flow cytometry was used to analyze the effect of ROS on apoptosis and autophagy mediated by apoptin. Then, the affect of ROS on apoptosis and autophagy mediated by apoptin was analyzed. Finally, the key genes leading to autophagy were analyzed by silencing different genes.Results: The results showed that apoptin can significantly increase the apoptosis and autophagy of liver cancer cells, and apoptin can cause mitophagy through the increase of NIX protein. Apoptin can also significantly reduce the level of cellular ROS, which is related to the autophagy and apoptosis of liver cancer cells caused by apoptin. The change of ROS may be a key factor causing apoptosis and autophagy. Conclusion: The above results indicate that the increase of ROS level after apoptin treatment of liver cancer cells leads to the loss of mitochondrial transmembrane potential, which leads to endogenous apoptosis and mitophagy while recruiting NIX. Therefore, ROS may be a key factor connecting endogenous apoptosis and mitophagy induced by apoptin in liver cancer cells.

The purpose of this study is to understand the state of the literature on nursing informatics education in Mainland China. We used the CNKI database (China National Knowledge Infrastructure) to extract all papers of nursing informatics education from 2009 to 2018. 20 high-frequency keywords, a co-word matrix, and three research themes were conducted on the 18 papers. These results can be used to improve our understanding of nursing informatics education in Mainland China.

This study aimed to understand the status of nursing informatics in Mainland China. Articles on nursing informatics, published between 2009 and 2018, were retrieved from the CNKI (China National Knowledge Infrastructure) database. A total of 51 papers were identified and analyzed. The journals, annual publications, and co-occurrence of keywords were analyzed with the bibliometric analysis. The result will help us better understand the nursing informatics research in mainland China.

The aim of this study was to understand the status and trend in alert override research over the past two decades (1999-2018). We used the Web of Science core collection (WoSCC) database to extract all papers of alert override in clinical decision support from 1999 to 2018. A total of 150 papers were identified, most (86.67%) being articles. This study presented the key bibliometric indicators such as annual publications, top 5 authors, institutions, countries, and co-occurrence of terms from the titles and abstracts. VOSviewer was used to visualize keywords knowledge maps. The results show that alert override research has a wide variety of research themes and a multidisciplinary character. This study provides a broad view of the current status and trends in alert override research. It may help researchers, clinicians and policymakers better understand alert override research field change and direction in the future.

This paper aims to investigate PhD nursing students' perceptions regarding a clinical informatics course. Open-ended questionnaires and reviews were used to explore the students' perception of the course. A total of 84.62% (11/13) students responded to the survey. Only four respondents had an understanding of clinical informatics and others did not. All the respondents considered clinical informatics to be a very important and useful course for PhD nursing students.

The purpose of the study is to identify research topics and hotspots in nursing informatics education during the period of 2009-2018. The relevant literature of nursing informatics education was retrieved from the Web of Science Core Collection (WoSCC). This study identified three research themes and hotspots in nursing informatics education using co-word analysis. The themes are curriculum, technology, and nursing informatics. The results provide useful information for researchers to research topic choices and in-depth research.

This study aims to identify research themes and hotspots in nursing informatics over the past decade. We retrieved literature published from the Web of Science Core Collection (WoSCC) between 2009 and 2018. The study identified four research themes by co-word analysis. Four clusters of keyword reflect four research themes in the field. The results will help researchers understanding the research themes of nursing informatics.

Background Apoptin, as a tumor-specific pro-apoptotic protein, plays an important anti-tumoral role, but its mechanism of autophagy activation and the interaction between autophagy and apoptosis have not been accurately elucidated. Here, we studied the mechanism of apoptin-induced apoptosis and autophagy and the interaction between two processes. Methods Using crystal violet staining and the CCK-8 assay, we analyzed the effect of apoptin in the inhibition of liver cancer cells in vitro and analyzed the effect of inhibiting liver cancer in vivo by establishing a nude mouse tumor model. Flow cytometry and fluorescence staining were used to analyze the main types of apoptin-induced apoptosis and autophagy. Subsequently, the relationship between the two events was also analyzed. Flow cytometry was used to analyze the effect of ROS on apoptin-mediated apoptosis and autophagy mediated by apoptin. The effect of ROS on two phenomena was analyzed. Finally, the role of key genes involved in autophagy was analyzed using gene silencing. Results The results showed that apoptin can significantly increase the apoptosis and autophagy of liver cancer cells, and that apoptin can cause mitophagy through the increase in the expression of NIX protein. Apoptin can also significantly increase the level of cellular ROS, involved in apoptin-mediated autophagy and apoptosis of liver cancer cells. The change of ROS may be a key factor causing apoptosis and autophagy. Conclusion The above results indicate that the increase in ROS levels after apoptin treatment of liver cancer cells leads to the loss of mitochondrial transmembrane potential, resulting in endogenous apoptosis and mitophagy through the recruitment of NIX. Therefore, ROS may be a key factor connecting endogenous apoptosis and autophagy induced by apoptin in liver cancer cells. Graphical abstract

This study aims to identify research themes and hotspots in nursing informatics over the past decade. We retrieved literature published from the Web of Science Core Collection (WoSCC) between 2009 and 2018. The study identified four research themes by co-word analysis. Four clusters of keyword reflect four research themes in the field. The results will help researchers understanding the research themes of nursing informatics.

This paper aims to investigate PhD nursing students’ perceptions regarding a clinical informatics course. Open-ended questionnaires and reviews were used to explore the students’ perception of the course. A total of 84.62% (11/13) students responded to the survey. Only four respondents had an understanding of clinical informatics and others did not. All the respondents considered clinical informatics to be a very important and useful course for PhD nursing students.

The purpose of the study is to identify research topics and hotspots in nursing informatics education during the period of 2009–2018. The relevant literature of nursing informatics education was retrieved from the Web of Science Core Collection (WoSCC). This study identified three research themes and hotspots in nursing informatics education using co-word analysis. The themes are curriculum, technology, and nursing informatics. The results provide useful information for researchers to research topic choices and in-depth research.

This study aimed to understand the status of nursing informatics in Mainland China. Articles on nursing informatics, published between 2009 and 2018, were retrieved from the CNKI (China National Knowledge Infrastructure) database. A total of 51 papers were identified and analyzed. The journals, annual publications, and co-occurrence of keywords were analyzed with the bibliometric analysis. The result will help us better understand the nursing informatics research in mainland China.

The aim of this study was to understand the status and trend in alert override research over the past two decades (1999–2018). We used the Web of Science core collection (WoSCC) database to extract all papers of alert override in clinical decision support from 1999 to 2018. A total of 150 papers were identified, most (86.67%) being articles. This study presented the key bibliometric indicators such as annual publications, top 5 authors, institutions, countries, and co-occurrence of terms from the titles and abstracts. VOSviewer was used to visualize keywords knowledge maps. The results show that alert override research has a wide variety of research themes and a multidisciplinary character. This study provides a broad view of the current status and trends in alert override research. It may help researchers, clinicians and policymakers better understand alert override research field change and direction in the future.

The purpose of this study is to understand the state of the literature on nursing informatics education in Mainland China. We used the CNKI database (China National Knowledge Infrastructure) to extract all papers of nursing informatics education from 2009 to 2018. 20 high-frequency keywords, a co-word matrix, and three research themes were conducted on the 18 papers. These results can be used to improve our understanding of nursing informatics education in Mainland China.

Ad-VT (Ad-Apoptin-hTERTp-E1a) is a type of oncolytic adenovirus with dual specific tumor cell death ability. It can effectively induce cell death of breast cancer cells and has better effect when used in combination with chemotherapy drugs. However, it has not been reported whether Ad-VT reduces the resistance of breast cancer cells to chemotherapy drugs. The purpose of this study is to investigate the effect of Ad-VT on drug resistance of Adriamycin-resistant breast cancer cells. For this, the effects of different doses of Ad-VT on the resistance of breast cancer cells to Adriamycin were analyzed using qualitative and quantitative experiments in vitro and in vivo. The Ad-VT can reduce the resistance of MCF-7/ADR to adriamycin, which is caused by the reduction of MRP1 protein level in MCF-7/ADR cells after treatment with Ad-VT, and MRP1 can be interfered with by autophagy inhibitors. Subsequently, the upstream signal of autophagy was analyzed and it was found that Ad-VT reduced the resistance of cells to doxorubicin by reducing the level of mTOR, and then the analysis of the upstream and downstream proteins of mTOR found that Ad-VT increased the sensitivity of MCF-7/ADR cells to adriamycin by activating AMPK-mTOR-eIF4F signaling axis. Ad-VT can not only significantly induce cell death in MCF-7/ADR cells, but also improved their sensitivity to Adriamycin. Therefore, the combination of Ad-VT and chemotherapy drugs may become a new strategy for the treatment of breast cancer in overcoming Adriamycin resistance.

BACKGROUND: To explore the suppressive effect of Apoptin-loaded oncolytic adenovirus (Ad-VT) on luciferase-labeled human melanoma cells in vitro and in vivo. METHODS: The stable luciferase-expressing human melanoma cells A375-luc or M14-luc were obtained by transfecting the plasmid pGL4.51 and selection with G418, followed by luciferase activity, genetic stability and bioluminescence intensity assays. In vitro, the inhibitory effects of Ad-VT on A375-luc or M14-luc were evaluated using the MTS cell proliferation, FITC-Annexin V apoptosis detection, transwell migration, Matrigel invasion and scratch assays. The inhibition pathway in Ad-VT-infected A375-luc and M14-luc cells were analyzed by JC-1 staining and Western-blot detection of mitochondrial apoptosis-related proteins. In vivo, the suppressive effects of Ad-VT on A375-luc or M14-luc were assessed by living imaging technology, tumor volume, bioluminescence intensity, survival curves and immunohistochemical analysis of the tumors from the xenograft tumor model BALB/c nude mice. RESULTS: The growth and migration of A375-luc and M14-luc were significantly inhibited by Ad-VT in vitro. The evaluations of A375-luc and M14-luc tumor models in BALB/c nude mice were successfully performed using living imaging technology. Ad-VT had an anti-tumor effect by reducing tumor growth and increasing survival in vivo. Ad-VT significantly changed the mitochondrial membrane potential by triggering the the mitochondrial release of apoptosis-related proteins, AIF (apoptosis inducing factor), ARTS (Apoptosis-Related Proteins), and Cyto-c (cytochrome c) from the mitochondria. CONCLUSION: Ad-VT reduced the mitochondrial membrane potential in A375-luc or M14-luc cells and induced the mitochondrial release of AIF, ARTS and Cyto-C. Ad-VT induced apoptosis in A375-luc or M14-luc cells via the mitochondrial apoptotic pathway.

Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. In our previous study, we demonstrated that Apoptin induced significant changes in the expression levels of endoplasmic reticulum stress (ERS) related proteins and caused a strong and lasting ERS response. The aim of this study was to explore the effects of ERS injury induced by Apoptin on the endoplasmic reticulum (ER) and the apoptotic pathway in mitochondria. ERS injury induced the intracellular levels of calcium (Ca2+) were determined by electron microscopy, flow cytometry and fluorescence staining. Mitochondrial injury was determined by mitochondrial membrane potential and electron microscopy. The relationship between Ca2+ level and mitochondrial injury on Apoptin-treating cells was analyzed using Ca2+ chelator, flow cytometry and fluorescence staining. Western blotting was used to investigate the levels of key proteins in the ER and the apoptotic pathway in mitochondria. We also investigated the in vivo effects of ERS injury on the ER and the mitochondrial apoptotic pathway via the immunohistochemical analysis of tumor tissues from HepG-2 cells acquired from nude mice undergoing xenografts. In vitro and in vivo experiments showed that Apoptin caused ERS injury and an imbalance in Ca2+, damaged the structure of the mitochondria, and increased the expression levels of Caspase-12, CHOP, AIF, HtrA2, Smac/Diablo, and Cyto-C. In summary, Apoptin induced apoptosis in HepG-2 cells via ERS and the mitochondrial apoptotic pathway. This study showed that Apoptin induced apoptosis in HepG-2 cells via ERS injury.

SummaryBackground One of the main challenges in the clinical treatment of lung cancer is resistance to chemotherapeutic drugs. P-glycoprotein (P-gp)-mediated drug resistance is the main obstacle to successfully implementing microtubule-targeted tumor chemotherapy. Purpose In this study, we explored the effect of Ad-hTERTp-E1a-Apoptin (Ad-VT) on drug-resistant cell lines and the molecular mechanism by which Ad-VT combined with chemotherapy affects drug-resistant cells and parental cells. Methods In vitro, cell proliferation, colony formation, resistance index (RI), apoptosis and autophagy assays were performed. Protein expression was analyzed by Western blotting. Finally, a xenograft tumor model in nude mice was used to detect tumor growth and evaluate histological characteristics. Results Our results showed that Ad-VT had an obvious killing effect on A549, A549/GEM and A549/Paclitaxel cancer cells, and the sensitivity of drug-resistant cell lines to Ad-VT was significantly higher than that of parental A549 cells. Compared with A549 cells, A549/GEM and A549/Paclitaxel cells had higher autophagy levels and higher viral replication ability. Ad-VT decreased the levels of p-PI3k, p-Akt and p-mTOR and the expression of P-gp. In vivo, Ad-VT combined with chemotherapy can effectively inhibit the growth of chemotherapy-resistant tumors and prolong the survival of mice. Conclusions Thus, the combination of Ad-VT and chemotherapeutic drugs will be a promising strategy to overcome chemoresistance.

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A – E (1 – 5), a new natural product, 5′-O-methylphaseolinisoflavan (6) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7 – 18). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.

Background Pressure dressings have been used after open hemorrhoidectomy to protect surgical wounds and manage postoperative bleeding for many years. However, pressure dressings may increase the incidence of postoperative complications, such as urinary retention, medical adhesive-related skin injury, and pain. A previous controlled trial included 67 patients who underwent Milligan-Morgan hemorrhoidectomy. The data indicated that the use of a nonpressure dressing after hemorrhoidectomy reduces the incidence of urinary retention and catheterization. However, the incidence of severe postoperative bleeding and other postoperative complications was not assessed. There is no consensus on whether it is necessary and beneficial to use a nonpressure dressing after hemorrhoidectomy. The results of this randomized clinical study will help answer this question. Methods In this study, we plan to include 186 patients who have undergone modified Milligan-Morgan hemorrhoidectomy, which only sutured external hemorrhoids to reduce the risk of bleeding. The purpose is to determine whether the use of nonpressure dressings after open hemorrhoidectomy is inferior to the use of pressure dressings in terms of severe postoperative bleeding and postoperative complications. The primary endpoints of the trial are the incidence of urinary retention within 24 h after surgery and the incidence of severe postoperative bleeding 1 h after dressing removal, which requires revision surgery within 24 h after the surgery. The secondary endpoints of the study are the pain score, anal distension score, postoperative use of analgesics, and incidence of medical adhesive-related skin injury, all of which will be assessed before removing the dressings. The length of hospitalization in days and hospitalization expenses will be recorded. Safety will be assessed with consideration of all adverse and severe adverse events related to the study treatment. Discussion The study received full ethics committee approval. The first patient was enrolled on 27 November 2020. The results of this trial will finally answer the question of whether a nonpressure dressing after open hemorrhoidectomy is necessary and beneficial. Trial registration Chinese Clinical Trial Registry ChiCTR2000040283. Registered on 28 November 2020.

Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai".This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments.First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylineosin (HE) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration.Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment.HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways.

Patients with heart failure are subjected to a substantial burden related to fluid overload symptoms. Exercise can help the lymphatic system function more effectively to prevent fluid build-up in tissues and interstitium, thus potentially mitigating the symptoms due to fluid overload. The objective of this systematic review was to examine the effects of exercise-based interventions on fluid overload symptoms among patients with heart failure. MEDLINE, Embase, Cochrane Library, and CINAHL databases were systematically searched for relevant studies published from inception to August 2021. We included randomized controlled trials that compared exercise-based interventions of different modalities and usual medical care for adult patients with heart failure and reported the effects of interventions on any symptoms related to fluid overload. A random-effects meta-analysis was used to estimate the effectiveness, and a subgroup analysis and univariate meta-regression analysis were used to explore heterogeneity. Seventeen studies covering 1086 participants were included. We found robust evidence indicating the positive effect of exercises in dyspnea relief (SMD = −0.48; 95%CI [−0.76, −0.19]; p = 0.001); the intervention length also influenced the treatment effect (β = 0.033; 95%CI [0.003, 0.063]; p = 0.04). Initial evidence from existing limited research showed that exercise-based intervention had positive effect to alleviate edema, yet more studies are needed to verify the effect. In contrast, the exercise-based interventions did not improve fatigue compared with usual care (SMD = −0.27; 95%CI [−0.61, 0.06]; p = 0.11). Findings regarding the effects of exercises on bodily pain, gastro-intestinal symptoms, and peripheral circulatory symptoms were inconclusive due to limited available studies. In conclusion, exercise-based interventions can be considered as an effective nonpharmacological therapy for patients with heart failure to promote lymph flow and manage fluid overload symptoms. Exercise-based interventions seem to have very limited effect on fatigue. More research should investigate the mechanism of fatigue related to heart failure. Future studies with high methodological quality and comprehensive assessment of symptoms and objective measure of fluid overload are warranted.

Apoptin is a protein that specifically induces apoptosis in tumor cells. The anti-tumorigenic functions of Apoptin, including autophagy activation and its interaction with apoptosis, have not been precisely elucidated. Here we investigate the main pathways of apoptin-mediated killing of human liver cancer cells, as well as its putative role in autophagy and apoptosis. The anti-proliferative effect of apoptin in liver cancer cells was analyzed in vitro by crystal violet staining and MTS detection, and also in vivo using a tumor-based model. The main pathway related to apoptin-induced growth inhibition in vitro was evaluated by flow cytometry and fluorescence staining. The relationship between apoptosis and autophagy on apoptin-treating cells was analyzed using apoptosis and autophagy inhibitors, mitochondrial staining, Annexin V-FITC/PI flow detection, LC3 staining, and western blotting. The effect of ROS toward the apoptosis and autophagy of apoptin-treating cells was also evaluated by ROS detection, Annexin V-FITC/PI flow detection, LC3 staining, and western blotting. Inhibition of apoptosis in apoptin-treating liver cancer cells significantly reduced the autophagy levels in vitro. The overall inhibition increased from 12 h and the effect was most obvious at 48 h. Inhibition of autophagy could increase apoptin-induced apoptosis of cells in a time-dependent manner, reaching its peak at 24 h. Apoptin significantly alters ROS levels in liver cancer cells, and this effect is directly related to apoptosis and autophagy. ROS appears to be the key factor linking apoptin-induced autophagy and apoptosis through the mitochondria in liver cancer cells. Therefore, evaluating the interaction between apoptin-induced apoptosis and autophagy is a promising step for the development of alternate tumor therapies.

Xiaokeyinshui (XKYS) formula, an anti-diabetic formula, was recorded in many ancient Chinese medical books. Xiaokeyinshui extract combination (XEC) originated from this ancient formula, consisting extracts of four herbal drugs, namely, Coptidis Rhizoma, Liriopes Radix, bitter melon, and Cassiae Semen.Therapeutic effects of Xiaokeyinshui extract combination (XEC) were assessed on diabetic rats.Herb extracts were prepared and mixed, yielding XEC. XEC were intragastrically given at doses of 260, 380 and 500 mg/kg/d to diabetic rats for 60 days. Anti-diabetic effects of XEC were studied, with measurement of body weight, and assessment of both glycemic control and lipid management. Measurement of oxidative stress and inflammatory cytokines were conducted in accordance to protocols of commercial kits. Parameters related to renal functions were also measured. Western blot (WB) analysis was performed to explore the anti-diabetic and renal protective mechanisms of XEC.Compared to diabetic control, XEC exhibited significant effects in both glucose-lowering and lipid management (p 0.01). Both oxidative stress and inflammatory cytokines were reduced after treatment of XEC for two months. In addition, XEC exhibited renal protective effects. WB analysis of liver tissue demonstrated that XEC achieved anti-diabetic effects through up-regulation of InsRα/IRS-1/PI3K/Akt/GLUT4 signaling pathway and phosphorylation of AMPK. In addition, renal protective effects were also achieved with down-regulation of RAGE and VEGF expressions in kidney.XEC exerts promising anti-diabetic and renal protective effects on diabetic rats in multi-target mechanisms. XEC could be a satisfying alternative treating T2DM and preventing diabetic nephropathy.

Background Heart failure (HF) imposes a substantial burden on patients and healthcare systems. Hospital-to-home transitional care, involving time-limited interventions delivered predominantly by nurses, was introduced to lighten this burden. This study aimed to examine the effectiveness and dose-response of nurse-led transitional care interventions (TCIs) on healthcare utilization among patients with HF. Methods Health-related databases were systematically searched for articles published from January 2000 to June 2020. We included randomized controlled trials (RCTs) that compared nurse-led TCIs with usual care for adults hospitalized with HF and reported the following healthcare utilization outcomes: all-cause readmissions, HF-specific readmissions, emergency department visits, or length of hospital stay. Random-effects meta-analysis, meta-regression analysis, and dose-response analysis were performed to estimate the treatment effects and explain the heterogeneity. Results Twenty-five RCTs including 8422 patients with HF were included. Nurse-led TCIs for patients with HF resulted in a mean 9% (RR = 0.91; 95% CI = 0.82 to 0.99; p = 0.04; I2 = 46%) and 29% (RR = 0.71; 95% CI = 0.60 to 0.84; p < 0.0001; I2 = 0%) reduction in all-cause and HF-specific readmission risks respectively compared to usual care. The interventions were also effective in shortening the length of hospital stay (MD = -2.37; 95% CI = -3.16 to -1.58; p < 0.0001; I2 = 14%). However, no significant reduction was found for emergency department visits (RR = 0.96; 95% CI = 0.84 to 1.10; p = 0.58; I2 = 0%). The effect of meta-regression coefficients on all-cause and HF-specific readmissions was not statistically significant for any prespecified trial-level characteristic. Dose-response analysis revealed that the HF-specific readmission risk decreased in a dose-dependent manner with the complexity and intensity of nurse-led TCIs. Conclusions Nurse-led TCIs were effective in decreasing all-cause and HF-specific readmission risks, as well as in reducing the length of hospital stay; however, the interventions were not effective in reducing the frequency of emergency department visits.

Ad-apoptin is a recombinant oncolytic adenovirus constructed by our laboratory that can express apoptin. It can selectively kill tumor cells without damaging normal cells. This study investigated the effects of Ad-apoptin on glycolysis, migration and invasion of non-small cell lung cancer. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, respectively. Glycolysis was investigated by glucose consumption, lactic acid production and glycolytic key enzyme protein levels. Migration and invasion were evaluated via wound healing, transwell assays and epithelial-mesenchymal transition (EMT) protein levels. The interaction between apoptin and AMPK was detected by Co-IP. A nude mice tumor model was established to investigate the anti-cancer role of Ad-apoptin in vivo. The results showed that Ad-apoptin inhibits cell viability and induces apoptosis of A549 and NCI–H23 cells. Ad-apoptin can reduce the glucose uptake and lactic production in lung cancer cells, and reduce the expression of related glycolysis-limiting enzymes. At the same time, Ad-apoptin inhibited the migration and invasion of lung cancer. Immunoprecipitation showed that apoptin and AMPK could interact directly. Moreover, knockdown of AMPK significantly attenuated the inhibitory effect of Ad-apoptin on glycolysis, migration and invasion of A549 and NCI–H23 cells. Ad-apoptin can inhibit the growth of tumors in nude mice. Compared with the control group, Ad-apoptin had a significant inhibitory effect on AMPK knockdown tumors. The immunohistochemical results of tumor tissues were consistent with those in vitro. Collectively, Ad-apoptin targets AMPK and inhibits glycolysis, migration and invasion of lung cancer cells through the AMPK/mTOR signaling pathway. This suggests that Ad-apoptin may have therapeutic potential for lung cancer by targeting AMPK activation.

In order to identify digital instrument characters 0∼9 and decimal point in different scenarios, a digital instrument recognition algorithm based on block feature fusion SSD is proposed. Because the identification of small targets is difficult, in order to preserve the spatial information of small targets, the algorithm first divides the low-dimensional feature map into blocks and then fuses with the backbone network during the feature extraction phase. Secondly, in the prediction stage, the high-dimensional feature map is deconvoluted and then merged with the low-dimensional features to obtain the feature map with both spatial information and semantic information. Finally, the prediction result is passed through the character processing module to obtain the final representation. The experimental results show that compared with the original SSD, the algorithm improves the AP (Average Precision) of the decimal point by 30% and the mAP (Mean Average Precision) by 5.8%. It can accurately identify many different instrument representations in different environments and is robust enough to meet practical applications.

The purpose of this study was to knock out two non-essential gene fragments (TC7L-TK2L and TJ2R) related to virulence, immunomodulation, and host range in the vaccinia virus Tian Tan strain (VTT), and combining with double-label screening and exogenous screening marker knockout techniques to construct attenuated strains with multiple gene deletions(rVTT-TC-TJ). The shuttle plasmids pSK-TC and pSK-TJ were constructed by designing 2 pairs of recombinant arms, combined with poxvirus early and late complex strong promoter pE/L and exogenous screening marker enhanced green fluorescent protein(EGFP). The results showed that knocking out the two gene fragments does not affect the replication ability of the virus and displays a good genetic stability. Furthermore, a series of in vivo and in vitro experiments demonstrate that although virulence of rVTT-TC-TJ is attenuated significantly, high immunogenicity was maintained. These results support the potential development of rVTT-TC-TJ as a safe viral vector or vaccine.

Background Transitional care interventions that bridge the care gap from hospital to home have proven to be effective in lessening the burden of healthcare systems by reducing hospital readmissions. Yet, the effects of transitional care interventions on patient-centered health outcomes of mortality, quality of life, and emotional distress remains unclear. Objectives To evaluate the effectiveness and dose-response of transitional care interventions on patient-centered health outcomes of mortality, quality of life, and emotional distress among individuals with heart failure and to identify the trial-level characteristics potentially affecting the overall effectiveness. Design Systematic review with random-effects meta-analysis, meta-regression, and dose-response analysis of randomized controlled trials comparing transitional care interventions with usual care in adult people hospitalized with heart failure. Data sources Electronic databases including MEDLINE, Embase, Cochrane Library, and CINAHL were systematically searched from January 1, 2000 to June 31, 2020. Review methods Authors independently reviewed the retrieved articles based on inclusion and exclusion criteria, extracted data, and assessed risk of bias using the Cochrane risk-of-bias tool version 2.0. We pooled data from each study using random-effects meta-analysis and performed meta-regression to explore the impact of pre-specified trial-level factors. Dose-response meta-analysis was conducted to examine the relationship between the intensity (i.e., frequency and duration of interventions) and complexity (i.e., number of intervention components) of transitional care interventions and the treatment effects. Results Data were synthesized from 42 trials covering a total of 10,784 people with heart failure. Comparing to usual care, transitional care interventions achieved pooled evidence of a mean 18% risk reduction on mortality (0.82, 95% CI 0.71 to 0.95, P = 0.009) and better improvement in quality of life (-4.37, 95% CI -7.20 to -1.54, P = 0.002). There were insufficient data to determine with certainty the effects on anxiety and depression. Meta-regression showed greater efficacy in trials that delivered the intervention by a multidisciplinary team. Dose-response analyses demonstrated that mortality and quality of life were improved with increased intensity and complexity of the transitional care interventions. Conclusions Transitional care interventions were effective in reducing mortality and improving quality of life for adult people with heart failure. The effects on emotional distress were inconclusive due to insufficient data, highlighting the need for further research. Registration number CRD42019132732

Objective To describe social problem solving in Chinese baccalaureate nursing students. Methods A descriptive cross-sectional study was conducted with a cluster sample of 681 Chinese baccalaureate nursing students. The Chinese Version of the Social Problem Solving scale was used. Descriptive analyses, independent t-test and one-way analysis of variance were applied to analyze the data. Findings The final year nursing students presented the highest scores of positive social problem-solving skills. Students with experiences of self-directed and problem-based learning presented significantly higher scores in Positive Problem Orientation subscale. The group with Critical thinking training experience, however, displayed higher negative problem solving scores compared with non-experience group. Conclusions Social problem solving abilities varied based upon teaching-learning strategies. Self-directed and problem-based learning may be recommended as effective way to improve social problem-solving ability. This article is protected by copyright. All rights reserved

This dataset is supplementary to our accepted article in Journal of Ethnopharmacology [1]. Xiaokeyinshui (XKYS) formula, an anti-diabetic formula, was recorded in many ancient Chinese medical books. Xiaokeyinshui extract combination (XEC) originated from this ancient formula, consisting extracts of four herbal drugs, i.e., Coptidis Rhizoma, Liriopes Radix, bitter melon, and Cassiae Semen. In this study, herb extracts were prepared and mixed, producing Xiaokeyinshui extract combination (XEC). The optimized formula of XEC was also investigated via uniform experimental design. Diabetes was induced in Kunming mice, using high-sugar-high-fat diet combined with injection of streptozotocin (STZ) intraperitoneally. Different formulae of XEC were intragastrically administered to diabetic mice for 28 days. Fasting blood glucose (FBG), oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), total cholesterol (TC), total triglyceride (TG) were measured to assess the anti-diabetic effects of each formula. Multivariate second degree polynomial model was applied in the fitting of metabolic parameters, and the extremum value of each regression model was calculated using grid algorithm. In addition, an optimized formula of XEC was subjected to validation experiment in mice model. This data could provide basis for a reasonable analysis for the optimization of the formula of XEC.

rVTT-TA35-TJ, an attenuated vaccinia virus Tian Tan strain (VTT), was constructed by knocking out two non-essential gene fragments (TA35R and TJ2R) related to virulence, immunomodulation, and host range; and by combining double marker screening with exogenous and endogenous selectable marker knock-out techniques. Here, the shuttle plasmids pSK-TA35 and pSK-TJ were constructed, containing two pairs of recombinant arms: early and late strong promoter pE/L and EGFP as an exogenous selectable marker. The recombinant vaccinia virus rVTT-TA35-TJ without exogenous selection markers was then obtained through homologous recombination technology and the Cre/loxP system. Knocking out the two gene fragments does not affect the replication ability of the virus and displays a good genetic stability. Furthermore, a series of in vivo and in vitro experiments demonstrate that although virulence of rVTT-TA35-TJ is attenuated significantly, high immunogenicity was maintained. These results support the potential development of rVTT-TA35-TJ as a safe viral vector or vaccine.

Goatpox virus (GTPV) is prevalent in goats and is associated with high mortality. This virus causes fever, skin nodules, lesions in the respiratory and lymph node enlargement. Considering the safety risks and side effects of vaccination with attenuated live GPTV vaccine strain AV41, an attenuated goatpox virus (GTPV-TK-ORF), was constructed by deleting non-essential gene fragments without affecting replication and related to the virulence and immunomodulatory functions of the goatpox virus AV41 strain (GTPV-AV41) using homologous recombination and the Cre (Cyclization Recombination Enzyme)/Loxp system. The results of both in vivo and in vitro experiments demonstrated that GTPV-TK-ORF was safer than wild type GTPV-AV41, possessed satisfactory immunogenicity, and could protect goats from a virulent GTPV-AV40 infection. Moreover, the IFN-γ, GTPV-specific antibody, and neutralizing antibody levels in the GTPV-TK-ORF-immunized group were significantly higher than that in the normal saline control group following immunization (P 0.01). Thus, GTPV-TK-ORF may be used as a potential novel vaccine and viral vector with good safety and immunogenicity.