Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

To develop a blue cap anticoagulant tube blood volume measuring card of to solve the problem of insufficient or excessive blood collection in clinical coagulation specimens.The device was composed of a measuring card,a transparent housing with a base and a tube holder.The measuring card was divided into qualified and unqualified areas,the housing was used to insert the card,the tube holder was used to place blood collection tubes.The device was used by clinical nurses to judge the adequacy of blood collection volume in blue cap anticoagulant tube.After the use of the device,the failure rate of clinical blue cap anticoagulation tube specimens submission was reduced from 6.71‰ to 2.73‰,shortened the time limit for specimen submission.At the same time,the device made the rejection judgment of department specimens more standardized and avoided the acceptance of unqualified specimens caused by subjective judgment errors.The device has simple structure,convenient operation and strong practicability,and has promotion value.

To investigate the expression of mRNA in esophageal cancer (ESCA) tissues and its potential and diagnostic and prognostic value by high-throughput sequencing data. Using the Cancer Genome Atlas Program (TCGA) database in USA by integrative bioinformatics analysis methods, the gene expression profiles and clinical data of 173 patients with ECSA were collected. The mRNA expression levels in ESCA tissue and para-cancerous tissue samples were analyzed using DESeq2, edgeR and limma to screen the differentially expressed genes (DEGs). DEGs-related protein network diagrams were drawn. GO and KEGG function enrichment analysis were performed and the hub genes were screened and the survival analysis of hub genes was analyzed. Genes related to the prognosis of ESCA were selected and their prognostic value in ESCA was analyzed. Finally, the receiver operating characteristic curve was drawn to evaluate its diagnostic value. The results showed that using TCGA cancer data, a total of 620 up-regulated DEGs and 668 down-regulated DEGs with significant differential expression between ESCA and para-cancerous tissues were screened. DEGs were mainly involved in receptor complexes, ubiquitin ligase complexes, etc., playing GTPase activity, phospholipid binding, and other molecular functions, and participating in the regulation of intracellular substance transport, small molecule metabolism, and other biological processes. Protein functional enrichment analysis showed that these proteins were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, Epstein-Barr virus infection, neutrophil extracellular trap formation, and other pathways involved in the formation and development process of ESCA. Survival analysis showed that the overall survival rate of ESCA patients with high expression of KIF4A, RAD51AP1, and CDKN3 was significantly shortened, and the difference was statistically significant ( P<0.05). Furthermore, the areas under the curve (AUC) of KIF4A, RAD51AP1, and CDKN3 for diagnosing esophageal cancer were 0.956, 0.951 and 0.979, respectively, with sensitivities and specificities both exceeding 80%. Additionally, ROC results of the combined diagnostic model of these three genes showed an AUC of 0.979, with sensitivities and specificities of 0.914 and 1, respectively. This indicates that KIF4A, RAD51AP1 and CDKN3 have individual or combined auxiliary diagnostic value for ESCA. In conclusion, KIF4A, RAD51AP1 and CDKN3 have high diagnostic efficiency for ESCA, and their increased expression is closely related to the prognosis, suggesting that these three genes could be used as auxiliary diagnostic and prognostic factors for ESCA.

Objective To investigate the role of macrophage migration inhibitory factor(MIF)on liver inflammation in mice with a-cute liver failure(ALF).Methods Eighteen male mice were randomly divided into normal group,model group and MIF antagonist ISO-1 group.D-galactose combined with lipopolysaccharide were used to induce ALF model.The serum levels of alanine aminotrans-ferase(ALT)、aspartate aminotransferase(AST)and total bilirubin(TBIL)were detected.The pathological changes of liver were ob-served by HE staining and the apoptosis of liver cells was observed by Tunel staining.The levels of MIF,CXC chemokine receptor 2(CX-CR2)and tumor necrosis factor-α(TNF-α)in mouse liver tissues were detected by enzyme-linked immunosorbent assay(ELISA)and the expression of MIF was observed by immunofluorescence.Results Compared with the normal group,the model group showed seri-ous liver tissue structure damage,increased hepatocyte apoptosis and decreased liver function.ISO-1 reduced liver tissue damage and hepatocyte apoptosis.The expression levels of MIF,CXCR2 and TNF-α in liver tissue of mice in model group was significantly in-creased,while ISO-1 could significantly reduce the expression levels of MIF,CXCR2 and TNF-α,with statistical significance(P＜0.05).Conclusion The expression of MIF is significantly increased in ALF,and inhibition of MIF can improve liver tissue injury and the expression of inflammatory factors,indicating that MIF plays an important role in ALF.

To investigate the expression of mRNA in esophageal cancer (ESCA) tissues and its potential and diagnostic and prognostic value by high-throughput sequencing data. Using the Cancer Genome Atlas Program (TCGA) database in USA by integrative bioinformatics analysis methods, the gene expression profiles and clinical data of 173 patients with ECSA were collected. The mRNA expression levels in ESCA tissue and para-cancerous tissue samples were analyzed using DESeq2, edgeR and limma to screen the differentially expressed genes (DEGs). DEGs-related protein network diagrams were drawn. GO and KEGG function enrichment analysis were performed and the hub genes were screened and the survival analysis of hub genes was analyzed. Genes related to the prognosis of ESCA were selected and their prognostic value in ESCA was analyzed. Finally, the receiver operating characteristic curve was drawn to evaluate its diagnostic value. The results showed that using TCGA cancer data, a total of 620 up-regulated DEGs and 668 down-regulated DEGs with significant differential expression between ESCA and para-cancerous tissues were screened. DEGs were mainly involved in receptor complexes, ubiquitin ligase complexes, etc., playing GTPase activity, phospholipid binding, and other molecular functions, and participating in the regulation of intracellular substance transport, small molecule metabolism, and other biological processes. Protein functional enrichment analysis showed that these proteins were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, Epstein-Barr virus infection, neutrophil extracellular trap formation, and other pathways involved in the formation and development process of ESCA. Survival analysis showed that the overall survival rate of ESCA patients with high expression of KIF4A, RAD51AP1, and CDKN3 was significantly shortened, and the difference was statistically significant ( P<0.05). Furthermore, the areas under the curve (AUC) of KIF4A, RAD51AP1, and CDKN3 for diagnosing esophageal cancer were 0.956, 0.951 and 0.979, respectively, with sensitivities and specificities both exceeding 80%. Additionally, ROC results of the combined diagnostic model of these three genes showed an AUC of 0.979, with sensitivities and specificities of 0.914 and 1, respectively. This indicates that KIF4A, RAD51AP1 and CDKN3 have individual or combined auxiliary diagnostic value for ESCA. In conclusion, KIF4A, RAD51AP1 and CDKN3 have high diagnostic efficiency for ESCA, and their increased expression is closely related to the prognosis, suggesting that these three genes could be used as auxiliary diagnostic and prognostic factors for ESCA.

AIM: To explore the synthesis of thermo-sensitive poly N-isopropylacry-lamide(PNIPAAm)and the petri dish grafted with PNIPAAm hydrogels by the electron accelerator, as well as the growth conditions and the biological characteristics of rabbit corneal stromal cells on thermo-sensitive PNIPAAm hydrogels, and the cell sheets obtained from the PNIPAAm hydrogels.METHODS: NIPAAm monomer was dissolved in 2-propanol at concentrations of 55% with 0.5% N,N'-Methylenebisacry-lamide(MBA). Solution(70 μL)was added and spread uniformly over 35 mm petri dish. These dishes were immediately subjected to irradiation. After follow-up treatment, rabbit corneal stromal cells were cultured on thermo-sensitive petri dish in vitro.RESULTS: According to the monomer formula and radiation synthesis scheme in this experiment, PNIPAAm can be synthesized on the surface of the petri dish. Rabbit corneal stromal cells grew well in the thermo- sensitive surface and can be separated into sheets.CONCLUSION: The single and multilayer carrier-free cell sheets can be obtained from the use of thermo-sensitive petri dish.

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 dynamic monitoring of citrulline (Cit) has guiding value for early enteral nutrition (EN) in patients with severe gastrointestinal injury. METHODS: A observational study was conducted. A total of 76 patients with severe gastrointestinal injury admitted to different intensive care units of Suzhou Hospital Affiliated to Nanjing Medical University from February 2021 to June 2022 were enrolled. Early EN was performed in 24-48 hours after admission as recommended by the guidelines. Those who did not terminate EN after 7 days were enrolled in the early EN success group, and those who terminated EN within 7 days due to persistent feeding intolerance or deterioration of general condition were enrolled in the early EN failure group. There was no intervention during the treatment. Serum Cit levels were measured by mass spectrometry at admission, before EN starting and EN 24 hours, respectively, and the changes in Cit within EN 24 hours (ΔCit) were calculated (ΔCit = EN 24-hour Cit-Cit before EN starting). Receiver operator characteristic curve (ROC curve) was plotted to investigate the predictive value of ΔCit for early EN failure, and the optimal predictive value was calculated. Multivariate unconditional Logistic regression was used to analyze the independent risk factors for early EN failure and death at 28 days. RESULTS: Seventy-six patients were enrolled in the final analysis, of which 40 succeeded in early EN and 36 failed. There were significant differences in age, main diagnosis, acute physiology and chronic health evaluation II (APACHE II) score at admission, blood lactic acid (Lac) before EN initiation and ΔCit between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 0.929, 95% confidence interval (95%CI) was 0.874-0.988, P = 0.018], ΔCit (OR = 2.026, 95%CI was 1.322-3.114, P = 0.001) and increased feeding rate within 48 hours (OR = 13.719, 95%CI was 1.795-104.851, P = 0.012) were independent risk factors for early EN failure in patients with severe gastrointestinal injury. ROC curve analysis showed that ΔCit had a good predictive value for early EN failure in patients with severe gastrointestinal injury [area under the ROC curve (AUC) = 0.787, 95%CI was 0.686-0.887, P < 0.001], and the optimal predictive value of ΔCit was 0.74 μmol/L (sensitivity was 65.0%, specificity was 75.0%). Combined with the optimal predictive value of ΔCit, "overfeeding" was defined as ΔCit < 0.74 μmol/L and increased feeding within 48 hours. Multivariate Logistic regression analysis showed that age (OR = 0.825, 95%CI was 0.732-0.930, P = 0.002), APACHE II score (OR = 0.696, 95%CI was 0.518-0.936, P = 0.017) and early EN failure (OR = 181.803, 95%CI was 3.916-8 439.606, P = 0.008) were independent risk factors for 28-day death in patients with severe gastrointestinal injury. The new variable "overfeeding" was also associated with an increased risk of death at 28 days (OR = 27.816, 95%CI was 1.023-755.996, P = 0.048). CONCLUSIONS Dynamic monitoring of Cit has guiding value for early EN in patients with severe gastrointestinal injury.
Humans ; Infant, Newborn ; Enteral Nutrition ; Citrulline ; APACHE ; Abdominal Injuries ; Cognition ; Thoracic Injuries

Objective:To explore the protective effect of AGK2, a selective inhibitor of sirtuin 2 (SIRT2), on the mitochondria of L02 hepatocytes induced by thioacetamide (TAA) and its related mechanism.Methods:Human-derived hepatocyte line L02 cells were cultured in vitro. Different concentrations of SIRT2 inhibitor AGK2 were used as intervention drugs. Cell counting kit-8 (CCK8) was used to detect the effects of different concentrations of AGK2 on the activity of L02 cells, and the appropriate concentration was selected as the AGK2 intervention group. The normal group was not given any drug intervention. The model group was given 90 mmol/L TAA for modeling. Low, medium and high dose AGK2 groups were added with 1, 2 and 4 μmol/L AGK2, respectively 2 h before modeling. CCK8 was used to detect cell activity in each group. Morphological changes of cells were observed under inverted light microscope. The relative protein expression levels of isocitrate dehydrogenase (IDH1), malate dehydrogenase (MDH1), SIRT2 and fission protein 1 homologue (FIS1) were detected by Western blot. The expression of SIRT2 in cells of each group was observed by confocal laser scanning microscope. The mitochondrial membrane potential of cells in each group was observed under a fluorescence microscope. Results:When AGK2 concentration was 1, 2 and 4 μmol/L, the survival rate of cells were 98.05%, 95.76% and 91.65%, respectively, with no statistical significance compared with normal group (all P>0.05). When AGK2 concentration was 8, 16, 32, 64, 128 μmol/L, the cell survival rate was significantly decreased compared with normal group (all P<0.05). Compared with the model group, the L02 cells in low, medium and high AGK2 groups had better activity and adherence, and the floating cells were significantly reduced. The higher the concentration of AGK2, the better the cell activity and adherence, and the less floating cells. Compared with the model group, the red fluorescence of L02 cells in AGK2 group was enhanced, while the green fluorescence was weakened. The higher the AGK2 concentration was, the stronger the red fluorescence was, and the weaker the green fluorescence was. Compared with the model group, the fluorescence of SIRT2 in L02 cells of low, medium and high AGK2 groups was weakened, and the higher the concentration of AGK2, the weaker the fluorescence of SIRT2. The protein expressions of IDH1 and MDH1 in L02 cells of low, medium and high AGK2 groups were significantly higher than those of model group (all P<0.05), and were positively correlated with the concentration of AGK2 ( r=0.818, P<0.05; r=0.960, P<0.05); the protein expressions of SIRT2 and FIS1 were significantly lower than those of the model group (all P<0.05), and were negatively correlated with the concentration of AGK2 ( r=-0.992, P<0.05; r=-0.998, P<0.05). Conclusions:AGK2 can reduce the mitochondrial membrane potential stimulated by TAA in L02 cells, increase the protein expression of IDH1 and MDH1, and inhibit the protein expression of SIRT2 and FIS1 in L02 cells in a dose-dependent manner.

Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China.
Acetylcholinesterase/metabolism* ; Animals ; Anthozoa/microbiology* ; Anti-Inflammatory Agents/pharmacology* ; Aspergillus/chemistry* ; Benzaldehydes/pharmacology* ; Mice ; RAW 264.7 Cells ; Signal Transduction