Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.
Animals ; Mice ; SARS-CoV-2/genetics* ; COVID-19 ; Vaccines, Synthetic/genetics* ; Genes, Reporter ; Bacteriophages ; Mice, Inbred BALB C

A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.

Purpose/Significance To explore the research status,research hotspots and frontiers in the field of clinical decision sup-port based on electronic medical records(EMR).Method/Process The bibliometric method and CiteSpace 6.2.R2 software are used to draw scientific knowledge graph of country/region distribution,author cooperation,institutional cooperation,keyword co-occurrence and clustering for visualized comparative analysis.Python is used for clustering hotspot mining and analysis.Result/Conclusion The field of clinical decision support based on EMR data shows a rapid development trend,with the United States and China as the main research countries and strong cooperation between domestic and foreign institutions.The keywords mainly involve EMR,artificial intelligence(AI),etc.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate whether cavitation induced by ultrasound stimulated perfluorobutane microbubbles can enhance the therapeutic effect of colchicine and reduce its side effects on acute gouty arthritis (AGA) in rats.Methods:The AGA rat model was established by injection of monosodium urate (MSU) crystals. The rats were randomly divided into 6 groups (A: blank control group, B: model control group, C: cavitation group, D: standard concentration drug group, E: low concentration drug cavitation group, F: standard concentration drug cavitation group) according to whether they were given different doses of colchicine. The area under the curve (AUC) of contrast-enhanced ultrasound (CEUS) was calculated at 7 h and 8 h after MSU injection to compare the effect of cavitation on ankle blood perfusion. The symptoms of AGA were evaluated according to the degree of ankle swelling and gait score at 24 h. The infiltration of neutrophils was detected by HE staining, and the inflammatory response was analyzed by detecting the level of interleukin-1β (IL-1β) in plasma. Vascular dilatation was analyzed by detecting the concentration of endothelial nitric oxide synthase (eNOS). The degree of adverse reactions in each group was analyzed by gastrointestinal reaction score.Results:The CEUS blood perfusion and AUC values of the three groups with cavitation (groups C, E and F) were significantly higher than those of the non-cavitation groups (groups A, B and D) (all P<0.05). Compared with group D, there were no significant differences in the degree of ankle swelling, gait score, and plasma IL-1β level in group E (all P>0.05), but the plasma eNOS concentration was higher and the incidence of gastrointestinal reactions was significantly lower in group E (all P<0.05). Compared with group D, the degree of ankle swelling and gait score in group F were decreased, and HE staining showed that the degree of synovial infiltration of neutrophils in the ankle joints of AGA rats in group F was lighter (all P<0.05), but there was no significant difference in plasma IL-1β level and the incidence of gastrointestinal reactions between group D and group F (all P>0.05). Conclusions:The cavitation of perfluorobutane microspheres stimulated by ultrasound can enhance the blood perfusion of the ankle joint of AGA rats, enhance the therapeutic effect of local colchicine, and help to reduce the dosage of colchicine and its side effects.

Objective:To investigate the effect of modified percutaneous closure in the treatment of ventricular septal rupture.Methods:This study is a retrospective cohort study. Forty-four patients with ventricular septal rupture who underwent percutaneous closure at the Fuwai Central China Cardiovascular Hospital from December 2017 to October 2023 were included. According to the closure method, patients were divided into the modified group (11 cases) and the traditional group (33 cases). Surgical success was defined as successful placement of the occluder. The operation time, X-ray intake, sheath bending rate, incidence of ventricular fibrillation and pericardial tamponade, and postoperative residual shunt were compared between the two groups.Results:The age of the patients was (75.0±5.7) years, with 20 (45%) males. There were 3 cases of operation failure in the traditional group, while all patients in the modified group were successfully occluded. The procedure time in the modified group was shorter than that in the traditional group (40 (35, 45) min vs. 60 (50, 65)min, P<0.001); X-ray dose intake was lower ((442.43±73.26)mGy vs. (784.45±247.78)mGy, P<0.001). There was no occurrence of sheath bending in the modified group, while the incidence of sheath bending in the traditional surgery group was 46% (15/33), and the difference was statistically significant ( P=0.017). Intraoperative ventricular fibrillation and pericardial tamponade occurred in 7 cases (21%) and 2 cases (6%) in the traditional group respectively, while none occurred in the modified group, but the differences between the groups were not statistically significant (both P>0.05). There was no significant difference in residual shunt between the two groups (3.6 (2.5, 4.3) mm vs. 4.0 (3.5, 4.5) mm, P=0.506). Conclusion:The procedure of modified ventricular septal rupture closure is more simplified, with a lower incidence ofventricular fibrillation and pericardial tamponade.

Objective:To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).Methods:Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).Results:The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c. 963G>A (p.Q321=) and c. 994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c. 963G>A was classified as a pathogenic variant (PVS1+ PM2_Supporting+ PM3), whilst the c. 994A>T was classified as a variant of uncertain significance (PM2_Supporting+ PP3). Conclusion:Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

Objective To explore the effect of decoction of Euphorbia fischeriana Steud.and jujuba(DEFSJ)against estrogen receptor(ER)negative(-)and ER positive(+)breast cancer via the PI3k/Akt pathway,and to provide a reference for the targeted treatment of breast cancer.Methods DEFSJ extract was prepared and analyzed using UHPLC-Triple Quad.DEFSJ containing serum(CS)was prepared via a serum pharmacology method.Different concentrations of DEFSJ-CS were applied to(ER-)MDA-MB-453 and(ER+)MCF-7 breast cancer cells in vitro for 48 h.The distribution of cells in different stages of the cellular cycle was evaluated using a Flow cytometer.DNA ladder assay was used to assess the degree of apoptosis,and the expression of PI3k/Akt pathway-related proteins was evaluated by Western blot assay.The expression of FoxO3a,FoxOla,and Bim mRNA was detected by Real-time quantitative PCR.Nuclear transposition of FoxO3a protein was analysed using a confocal laser microscopy.Results Five batches of DEFSJ extract were analyzed using UPLC,and the result showed that the preparation technology was feasible and the quality was controllable,ensuring the accuracy of the pharmacological experiment result.DEFSJ-CS blocked cells in the G2/M phase(P＜0.05,P＜0.01).Cells treated with DEFSJ-CS displayed the typical apoptotic ladder in the DNA ladder experiment.Compared with the negative control cells,the DEFSJ-CS group cells had decreased protein expression of p-PI3k,p-Akt,p-FoxO3a,and p-FoxO1a(P＜0.05,P＜0.01);increased protein expression of Bim(P＜0.05);decreased mRNA expression of FoxO3a and FoxO1a(P＜0.05,P＜0.01);increased mRNA expression of Bim(P＜0.05,P＜0.01);and enhanced nuclear translocation of FoxO3a protein.The data showed that DEFSJ-CS had a stronger effect on(ER-)MDA-MB-453 cells than(ER+)MCF-7 cells.Conclusions The regulatory effect of DEFSJ extract on anti-breast cancer involves the PI3k/Akt pathway,and the effect varies with phenotypic differences.

OBJECTIVE: To explore the risk factors for poor prognosis in sepsis-associated acute kidney injury (SA-AKI) and establish a nomogram predictive model. METHODS: The clinical data of patients with SA-AKI admitted to the department of critical care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2019 to September 2022 were retrospectively analyzed, including demographic information, worst values of blood cell counts and biochemical indicators within 24 hours of SA-AKI diagnosis, whether the patient received renal replacement therapy (RRT), mechanical ventilation, vasopressor therapy during hospitalization, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), fibrinogen-to-albumin ratio (FAR) within 24 hours of diagnosis, acute kidney injury (AKI) staging, total length of hospital stay, length of intensive care unit (ICU) stay, and others. According to the 28-day outcome, the patients were divided into survival group and death group, and the indicators between the two groups were compared. Univariate and multivariate Logistic regression analyses were used to screen for risk factors associated with mortality in SA-AKI patients. A nomogram predictive model for SA-AKI prognosis was constructed based on the identified risk factors. Receiver operator characteristic curve (ROC curve) and calibration plots were generated to evaluate the predictive value of the nomogram model for SA-AKI prognosis. RESULTS: A total of 113 SA-AKI patients were included, with 67 in the survival group and 46 in the death group. The 28-day mortality among SA-AKI patients was 40.7%. The comparison between the two groups showed that there were statistically significant differences in age ≥ 65 years, AKI stage, mechanical ventilation, vasopressors, RRT, length of ICU stay, and laboratory indicators cystatin C (Cys C), fibrinogen (Fib), and FAR. Multivariate Logistic regression analysis showed that age ≥ 65 years [odds ratio (OR) = 7.967, 95% confidence interval (95%CI) was 1.803-35.203, P = 0.006], cystatin C (OR = 7.202, 95%CI was 1.756-29.534, P = 0.006), FAR (OR = 2.444, 95%CI was 1.506-3.968, P < 0.001), and RRT (OR = 7.639, 95%CI was 1.391-41.951, P = 0.019) were independent risk factors for mortality in SA-AKI patients. ROC curve analysis showed that the area under the ROC curve (AUC) for age ≥ 65 years, cystatin C, FAR, and RRT in predicting SA-AKI patient mortality were 0.713, 0.856, 0.911, and 0.701, respectively. A nomogram predictive model for SA-AKI patient prognosis was constructed based on age ≥ 65 years, cystatin C, FAR, and RRT, with an AUC of 0.967 (95%CI was 0.932-1.000) according to ROC curve analysis. The calibration plot indicated good consistency between predicted and actual probabilities. CONCLUSIONS Age ≥ 65 years, cystatin C, FAR, and RRT are independent risk factors for mortality in SA-AKI patients. The nomogram predictive model based on these four factors can accurately predict SA-AKI patient prognosis, helping physicians adjust treatment strategies in a timely manner and improve patient outcomes.
Humans ; Aged ; Cystatin C ; Retrospective Studies ; Intensive Care Units ; Sepsis/diagnosis* ; Acute Kidney Injury/therapy* ; Prognosis ; ROC Curve ; Fibrinogen