Oncolytic virotherapy is a promising therapeutic approach treating tumors, where oncolytic viruses (OVs) can selectively infect and lyse tumor cells through replication, while also triggering long-lasting anti-tumor immune responses. Vaccinia virus (VV) has emerged as a leading candidate for use as an OV due to its broad cytophilicity and robust capacity to express exogenous genes. Consequently, oncolytic vaccinia virus (OVV) has entered clinical trials. This review provides an overview of the key strategies used in the development of OVV, summarizes the findings from clinical trials, and addresses the challenges that must be overcome in the advancement of OVV-based therapies. Furthermore, it explores potential future strategies for enhancing the development and clinical application of OVV, intending to improve tumor treatment outcomes. The review aims to facilitate the further development and clinical adoption of OVV, thereby advancing tumor therapies.
Vaccinia virus/physiology* ; Humans ; Oncolytic Virotherapy/methods* ; Oncolytic Viruses/physiology* ; Neoplasms/therapy* ; Animals

Nutritional support therapy is one of the extremely important treatment methods for patients in the intensive care unit. Timely and effective nutritional support regimens can improve patients' immune function, reduce complications, and optimize clinical outcomes. Energy expenditure is influenced by multiple factors, including patients' baseline characteristics (such as physical condition, gender, age) and dynamic changes in indicators (such as body temperature, nutritional support regimens, and therapeutic interventions). The currently recognized "gold standard" for accurately assessing energy metabolism in clinical practice is the indirect calorimetry system, also known as the metabolic cart. This device monitors carbon dioxide production and oxygen consumption in real time and uses specific algorithms to estimate the metabolic proportions of the three major nutrients (carbohydrates, fats, and proteins) in energy expenditure. An appropriate nutrient ratio helps maintain the balance between supply and demand in the body's nutritional metabolism. In the management of critically ill patients, the application of the metabolic cart enables personalized nutritional therapy, avoiding over- or under-supply of energy and optimizing the use of medical resources. Furthermore, with real-time, quantitative data support from the energy metabolism monitoring system, clinicians can develop more precise nutritional intervention strategies, thereby improving patient prognosis. This article provides a systematic review of the technical features of the metabolic cart and its application value in various critical care scenarios, aiming to offer a reference for indirect calorimetry in clinical practice.
Humans ; Critical Illness/therapy* ; Nutritional Support ; Energy Metabolism ; Calorimetry, Indirect

ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy （BQT） on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori （HP） positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT， followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT， followed by 4 weeks of oral probiotic placebo. ¹³C urea breath test was used to evaluate the clinical efficacy， gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention， and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups （P>0.05）. Before the intervention， there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention， patients in the probiotic group had significantly lower pain scores on acid reflux （1.10±0.30 vs 1.35±0.53， P<0.05） and stomach or abdominal hunger than in the placebo group （1.07±0.26 vs 1.30±0.52， P<0.05）. Through the before-and-after comparison of the probiotic group， the scores of abdominal pain （1.24±0.44 vs 1.58±0.71， P<0.05）， stomach or abdominal hunger （1.07±0.26 vs 1.27±0.45， P<0.05） and dry and hard stool （1.24±0.49 vs 1.48±0.75，P<0.05） were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy， but it does not improve the eradication rate of HP.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Objective To observe the impact of semi-solidification enteral nutrition on feeding tolerance,nutritional and infection related indicators,and prognosis in neurocritical patients.Methods Adopting the prospective research method,the neurocritical patients who were admitted to the department of intensive care unit(ICU)of the First Affiliated Hospital of Ningbo University from December 2021 to May 2022 and had to stay in the nasogastric tube for enteral nutrition were selected as the study subjects,pectin was added to achieve the semi-solidification of enteral nutrition,and the patients were divided into pectin group and control group according to the principle of randomized control,with 25 cases in each group.Enteral nutrition was started within 24-48 hours of admission to the ICU in all patients,and pectin plus continuously pumped enteral nutrition preparation was given in the pectin group and continuously pumped enteral nutrition preparation in the control group,all of which was used continuously for more than 7 days.Differences in albumin,prealbumin,Glasgow coma scale(GCS),acute physiology and chronic health evaluation Ⅱ(APACHEⅡ),sequential organ failure assessment(SOFA),procalcitonin(PCT),interleukin-6(IL-6)and C-reactive protein(CRP)were compared between the two groups before and after 7 days of treatment,and enteral nutrition compliance rates at 3 days and 7 days of treatment,as well as the incidence of enteral nutrition intolerance(including vomiting,diarrhea,constipation,aspiration and bloating),along with the length of ICU stay and 28 days prognosis were observed.Results There were no statistically significant differences between the two groups in general clinical data[including gender,age and body mass index(BMI)]and pre-treatment GCS score,APACHEⅡ score,SOFA score,albumin,prealbumin,PCT,IL-6 and CRP levels.The incidence of vomiting,diarrhea,constipation,and bloating during enteral nutrition was significantly lower in the pectin group than those in the control group[vomiting:4.0％(1/25)vs.24.0％(6/25),diarrhea:8.0％(2/25)vs.32.0％(8/25),constipation:20.0％(5/25)vs.65.0％(13/25),bloating:12.0％(3/25)vs.36.0％(9/25),all P<0.05],but the difference in the incidence of aspiration compared with the control group was not statistically significant[4.0％(1/25)vs.16.0％(4/25),P>0.05].Caloric compliance with enteral nutrition was significantly higher in the pectin group than in the control group at both 3 days and 7 days of treatment[3 days of treatment:48.0％(12/25)vs.20.0％(5/25),7 days of treatment:88.0％(22/25)vs.60.0％(15/25),both P<0.05],and the prealbumin level was significantly higher in the pectin group than in the control group at the end of 7 days treatment(mg/L:248.08±43.99 vs.221.64±33.95,P<0.05).There was no statistically significant difference in the comparison of GCS score,APACHEⅡ score,SOFA score,PCT,IL-6,CRP,length of ICU stay,and 28 days mortality between the two groups after treatment.Conclusion The administration of semi-solidification enteral nutrition reduces the incidence of enteral nutrition intolerance,improves caloric intake and nutritional status in neurocritical patients,but has no significant effect on infection indicators and prognosis.

Purpose/Significance To introduce the knowledge graph technology in the field of electronic information into the study of traditional Chinese medicine(TCM)terminology,and to demonstrate the dialectical relationship between the therapeutic effects of TCM and its nature,flavor,meridians and TCM diseases in a vivid way.Method/Process The top-down ontology construction method is adopted to build the top-level structure of TCM ontology on the Protégé platform.Taking the 2020 edition of the Chinese Pharmacopoeia as the data source,the TCM information in the pharmacopoeia is split and extracted,and the information of each axis is sorted,disambiguated and nor-malized.With the help of the Protégé platform,entities and relationships are created,and the TCM triple data is output in RDF data for-mat.Finally,the Neo4j graph database is used to store and display the RDF data to form a systematic TCM knowledge graph.Result/Con-clusion It mainly realizes the construction of the knowledge graph of TCM in the pharmacopoeia,and fully reveals the complex knowledge system structure in the field of TCM through data statistical analysis,knowledge measurement and drawing of visual graphics.

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and pre-DIC status in sepsis patients. METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation. RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7％,22.0％and 31.5％,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P＜0.05).On day 1,the SIC score with a cut-off value＞3 had a significantly higher sensitivity(72.00％)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00％,SAC status 52.00％;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P＜0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95％confidence interval[95％CI]:0.060-0.783,P=0.018)and SAC(adjusted HR=0.146,95％CI:0.041-0.513,P=0.003). CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Objective To investigate the effect of dexmedetomidine on renal function in patients with septic-associated acute kidney injury(SAKI).Methods A prospective cohort study was conducted in 180 patients with sepsis admitted to ICU in the Second Affiliated Hospital of Guangdong Medical University from October 2021 to April 2023.According to the principle of randomized controlled trials,60 non-acute kidney injury(AKI)patients were divided into S-D group(n = 30,dexmedetomidine + conventional treatment)and S group(n = 30,conventional treatment),and the occurrence and disease score of AKI after treatment were compared between the two groups.A total of 120 AKI patients were divided into SA-D-RT group(n = 30,dexmedetomidine + blood purification + conven-tional treatment),SA-D group(n = 30,dexmedetomidine + conventional treatment),SA-RT group(n = 30,blood purification + conventional treatment)and SA group(n = 30,conventional treatment).Renal function,inflammatory factor level and disease change of the four groups were compared after treatment.Results After treatment,the inci-dence of AKI in S-D group was lower than that in S group,and the APACHEII score and SOFA score in S-D group were lower than those in S group on the 7th day after treatment(P<0.05).After 7 days of treatment,the level of Scr,BUN and CysC in the 4 groups was significantly lower than that on the 1st and 3rd day,and those in the SA-D-RT group were lower than those in the SA-D group,SA-RT group and SA group(P<0.05).After 7 days of treatment,the level of CRP,PCT,TNF-α,IL-6 and IL-1β in four groups was significantly decreased compared with on the 1st and 3rd day,and the level of CRP,PCT,TNF-α,IL-6 and IL-1β in SA-D-RT group was lower than that in SA-D group,SA-RT group and SA group(P<0.05).After 7 days of treatment,the APACHEII score and SOFA score of the four groups were significantly lower than on the 1st and 3rd day,and the scores of the SA-D group were lower than those of the SA-D group,the SA-RT group and the SA group(P<0.05).Conclusion Dexmedetomidine can effectively reduce the incidence of AKI,affect the expression level of renal function markers and inflammatory factors in serum of SAKI patients,and improve the condition of patients.

Objectives:To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy.Methods:The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival.Results:Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis ( P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions:The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.