Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

Human alphaherpesvirus 2 (HSV-2) is the main pathogen resulting human genital herpes, which poses a major threat to the socio-economic development, while there is no effective vaccine. In this study, we developed a novel lipopolyplex (LPP)-delivered mRNA vaccine expressing the HSV-2 envelope glycoprotein gD and evaluated its immunogenicity in mice. The mRNA vaccine was prepared from the genetically modified gD mRNA synthesized in vitro combined with the LPP delivery platform and it was named gD-ORI mRNA. The expression of gD antigen in the mRNA vaccine was validated in vitro by Western blotting and indirect immunofluorescence assay, then the immune responses induced by this mRNA vaccine in mice were evaluated. The immunization with gD mRNA alone induced strong humoral and cellular immune responses in mice. Robust and long-lasting gD-specific IgG antibodies were detected in the mouse serum after booster immunization with gD-ORI mRNA. The immunized mice exhibited a Th1/Th2 balanced IgG response and robust neutralizing antibodies against HSV-2, and a clear dose-response relationship was observed. The gD-specific IgG antibodies were maintained in mice for a long time, up to 18 weeks post-booster immunization. At the same time, multifunctional gD-specific CD4⁺ and CD8⁺ T cells in vaccinated mice were detected by intracellular cytokine staining (ICS). This novel gD-expressing mRNA vaccine delivered by LPP induces strong and long-lasting immune responses in mice post booster immunization and has a promising prospect for development and application. This study provides scientific evidence and reference for the development of a new mRNA vaccine for HSV-2.
Animals ; Herpesvirus 2, Human/genetics* ; Viral Envelope Proteins/genetics* ; Mice ; Herpes Genitalis/immunology* ; RNA, Messenger/immunology* ; Female ; Mice, Inbred BALB C ; Antibodies, Viral/blood* ; mRNA Vaccines/immunology* ; Antibodies, Neutralizing/blood* ; Humans

Objective To investigate the correlation between CT parameters of erector spinae muscle(ESM)and pulmonary function in elderly patients with chronic obstructive pulmonary disease(COPD),and to analyze its predictive value for the prognosis of patients.Methods A total of 120 COPD patients were included as the case group(including 60 cases in stable stage and 60 cases in acute exacerbation stage),and 60 smokers were selected as the control group.The differences of ESM CT parameters and pulmonary function parameters in each group were compared.According to the prognosis of COPD,patients were divided into good prognosis group(n=106)and poor prognosis group(n=14),and the predictive efficacy of ESM CT parameters on the prognosis of COPD patients was analyzed.Results The pulmonary function parameters,ESM cross sectional area(CSA)(ESMCSA)and ESM local volume in the case group were significantly lower than those in the control group(P<0.05).ESMCSA and ESM local volume were positively correlated with inspiratory capacity(IC),vital capacity(VC),forced vital capacity(FVC)and forced expiratory volume in one second(FEV1)(P<0.001).The average muscle density of ESM was positively correlated with IC,VC and FVC(P<0.05),but not with FEV1.The area under the curve(AUC)of ESMCSA and ESM local volume in predicting poor prognosis of COPD patients was 0.769[95%confidence interval(CI)0.661-0.876]and 0.827(95%CI 0.734-0.919),respectively.Conclusion There is a certain correlation between the CT parameters of ESM and the pulmonary function parameters of COPD patients,among which the ESMCSA and the ESM local volume have high predictive efficacy for the prognosis of COPD patients.

Objective:To evaluate the effect of patent foramen ovale on the development of post-operative stroke in the patients undergoing non-cardiac surgery using a meta-analysis approach.Methods:A comprehensive search was conducted across multiple databases including PubMed, Embase, Web of Science, CINAHL, Cochrane Library, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, and China Journal Full Text Database.The inclusion criteria encompassed studies assessing the correlation between patent foramen ovale and post-operative stroke.The primary outcome measure focused on the incidence of post-operative stroke, and secondary outcome measures comprised mortality, myocardial infarction rate, and readmission rate within 30 days after surgery. The quality of literature meeting the inclusion criteria was evaluated and data were extracted, and then meta-analysis was conducted using RevMan 5.4 software.Results:Eight retrospective cohort studies involving 21 142 237 patients were included.The results of meta-analysis showed that patent foramen ovale was associated with post-operative stroke and readmission within 30 days after surgery.There were no significant differences in all-cause mortality and myocardial infarction rates between patent foramen ovale group and mon-patent foramen ovale group ( P>0.05). Conclusions:Patent foramen ovale can increase the risk of post-operative stroke in the patients undergoing non-cardiac surgery.

Gastrointestinal graft versus host disease is one of the most severe complications after hematopoietic stem cell transplantation, which can occur in patients of any age groups. Its clinical manifestations include nausea, vomit, abdominal pain, diarrhea and the like. Severe gastrointestinal graft versus host disease could directly influence the patients' clinical prognosis and therapeutic efficacy of transplantation. Here we had a review of the research progress on nutritional support and diet management strategies for gastrointestinal graft versus host disease. It is of great clinical significance to form a step-wise nutritional support model to reduce the risk of malnutrition in patients with gastrointestinal graft versus host disease, which would contribute to improving patients' general condition, relieving digestive tract symptoms, and reducing the risk of complications.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

Objective:To explore the association between different feeding patterns, emotional states, and salivary oxytocin (OT) levels during breastfeeding.Methods:From January to December 2019, 153 pairs of 3-month-old infants and their mothers were recruited from 4 maternal and child health hospitals in Chongqing, Liuzhou, Dalian and Hangzhou in China.Saliva samples were collected from the mothers at the first 5 minutes of feeding, 5 minutes during feeding, and 10 minutes after feeding.Edinburgh postnatal depression scale (EPDS) was used to evaluate maternal depression.Infants were divided into exclusive breastfeeding group and artificial feeding group according to feeding patterns.ELISA of salivary oxytocin was performed by ELISA kits, and the OT levels measured at the 3 time points were converted using linear interpolation.Area under the curve with respect to ground(OTAUCG) was used to represent the total concentration of salivary OT during the mother's breastfeeding.SPSS 25.0 software was used for statistical analysis.Multiple linear regression analysis and two factors analysis of variance were used to explore the association between different feeding methods, emotional state and salivary oxytocin during breastfeeding.Results:The results of the two factors analysis of variance showed that the interaction between feeding pattern and mother's emotion was not significant ( F=2.440, P=0.120), the main effect of mother's emotion was not significant ( F=0.380, P=0.539), and the main effect of feeding style was significant ( F=3.350, P=0.021). The level of OTAUCG under pure breastfeeding ((151 561.47±75 738.11) pg/mL) was higher than that under artificial feeding ((122 269.03±65 029.88) pg/mL), and the difference was statistically significant ( P=0.02). There was no statistically significant difference in OTAUCG levels between mothers with normal emotions ((146 106.37±75 106.76) pg/mL) and mothers with depressed emotions ((129 079.56±67 565.87) pg/mL) ( P=0.221). Multiple stepwise regression analysis showed that artificial feeding had a negative predictive effect on maternal salivary OT levels compared to exclusive breastfeeding( β=-0.211, t=-2.513, P=0.013). Conclusion:Feeding pattern is a factor that affects the mother's salivary OT level, and breastfeeding can improve the mother's OT level.

Objective:To investigate the effect of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) on sizes and components of thrombi in patients with acute ischemic stroke (AIS) after mechanical thrombectomy (MT).Methods:Ninety-eight AIS patients accepted MT in Department of Neurology, Huaian First Hospital Affiliated to Nanjing Medical University from June 2018 to June 2022 were enrolled; they were divided into bridging therapy group and direct thrombectomy group according to the treatments. Baseline data, prognoses and thrombus features between the 2 groups were compared.Results:No significant differences were observed between the 2 groups in terms of age, gender, previous medical history, baseline scores, sites and types of vascular occlusion, TOAST causative classifications, time frame, MT frequencies and techniques, successful recanalization, or prognoses 90 d after MT ( P>0.05). Compared with the direct thrombectomy group, the bridging therapy group had significantly reduced thrombus area (37[22, 78] mm 2vs. 27[14, 62] mm 2) and areas of major pathological components [red blood cells: 16.1([9.0, 37.4] mm 2vs. 11.8[6.1, 22.1] mm 2, fibrin/platelets: 19.5[9.5, 26.4] mm 2vs. 10.7[5.0, 22.8] mm 2, white blood cells: 4.0[2.2, 8.0] mm 2vs. 2.4[1.4, 5.7] mm 2, P<0.05); however, no significant differences in proportions of areas of major pathological components were noted between the 2 groups of patients ( P>0.05). Conclusion:The rt-PA intravenous thrombolysis can significantly reduce the thrombi volume and decrease the contents of major thrombus components in AIS patients after MT, but not change the proportions of major pathological components in thrombi.

Objective:To establish a method for determintation of chlorogenic acid and linarin in Yejuhua granules by HPLC.Methods:We applied HPLC methods. The Kromasil 100-5 C18 column (250 mm×4.6 mm,5 μm) was used, the mobile phase was acetonitrile-0.4%H 3PO 4 solution (gradient elution), the flow rate was 1.0 ml/min, the dection wavelenghth was 334 nm and the column temperture was 32 ℃. Results:Chlorogenic acid and buddleoside had good linearity in the ranges of 0.30-1.50 μg ( r2=0.999 1) and 0.12-0.62 μg ( r2=0.999 8), respectively. The average recoveries were 99.70% and 96.67%, with RSD<2%, respectively. Conclusion:The method is simple, rapid, reliable, efficient, and can be used for determination of chlorogenic acid and buddleoside in Yejuhua Granules.

The aim of this study was to develop a semi-quantitative immunochromatographic method for rapid detection of Newcastle disease virus (NDV) antibodies by expressing HN protein in rice endosperm bioreactor. The recombinant plasmid pUC57-HN was digested by MlyⅠ and XhoⅠ to retrieve the HN gene, while the intermediate vector pMP3 containing promoter, signal peptide and terminator was digested by NaeⅠ and XhoⅠ. The HN gene and the linearized pMP3 were purified and ligated to form a recombinant plasmid pMP3-HN1. Subsequently, pMP3-HN1 and plant vector pCAMBIA1300 were digested by EcoRⅠ and Hind Ⅲ, and the HN1 gene was cloned into pCAMBIA1300. The recombinant plasmid pCAMBIA1300-HN1 was introduced into Agrobacterium tumefaciens EHA105 by electrotransformation, and the pCAMBIA1300-HN1 was transferred into rice callus by agrobacterium-mediated method. After dark culture, callus screening, differentiation, rooting and transplanting, transgenic rice seeds were obtained 4 months later. PCR identified that the HN gene has been inserted into the rice genome. SDS-PAGE and Western blotting indicated that the HN protein was successfully expressed in the positive rice endosperm. The purity of the HN protein was more than 90% by SP cation exchange chromatography and gel filtration chromatography. According to the national standards for the diagnostic techniques of Newcastle disease HI test (HI≥4log₂, positive antibody reaction), a colloidal gold labeled purified HN protein was used to prepare a semi-quantitative test strip by double-antibody sandwich method for rapid detection of NDV antibody. The results showed that the test strip did not cross-react with positive sera against other viruses, and the sensitivity of the test strip reached 1:102 400 for standard positive sera of Newcastle disease. Testing of a total of 308 clinical sera showed that the compliance rate of the test strip with HI test was 97.08%, and the Kappa value was 0.942. In conclusion, high purity recombinant HN protein was obtained from rice endosperm, and a simple, rapid, highly sensitive and highly specific semi-quantitative immunochromatographic strip was developed. The test strip could be used for immune evaluation of the Newcastle disease vaccine.
Animals ; Antibodies, Viral ; Chickens ; HN Protein/metabolism* ; Newcastle Disease/prevention & control* ; Newcastle disease virus/metabolism* ; Oryza/genetics*