AIM:To observe the effect of dexme-detomidine(DEX)on cerebral ischemia and reperfu-sion(I/R)injury and investigate the possible mecha-nism of nuclear factor erythroid derived 2-like 2(Nrf2)mediated ferroptosis on hippocampal neu-rons.METHODS:The oxygen glucose deprivation/reoxygenation(OGD/R)model in rat primary cul-tured hippocampal neurons was simulated,DEX(50 μmol/L)and Nrf inhibitor BRU(100 nmol/L)were used to observe the changes of ROS levels by DHE fluorescence probe.The middle cerebral ar-tery occlusion model in male SD rats were estab-lished,the degree of neurological impairment was detected by Longa score,and cerebral infarct size was detected by TTC staining.The Fe2+concentra-tion and levels of oxidative stress related factors were detected,oxidative stress and ferroptosis re-lated protein expressions were detected by West-ern blot.RESULTS:The fluorescence intensity of DHE in OGD/R+Dex Group was lower than that in CON group,and the fluorescence intensity of DHE in OGD/R+DEX+BRU group was higher than that in OGD/R+Dex group.Compared with Sham group,the Longa score and cerebral infarct size in I/R group were significantly increased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were significantly decreased.MDA and Fe2+concentrations were in-creased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were decreased,and TFR1 protein expression was increased.Compared with I/R group,in DEX+I/R group,the Longa score and ce-rebral infarct size were decreased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were increased.MDA and Fe2+concentrations were decreased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were increased,and TFR1 protein expression was decreased.The Nrf2 inhibitor Bru reversed the role of DEX.CONCLUSION:DEX protects against ce-rebral I/R injury through activating Nrf2 signaling pathway and inhibiting ferroptosis in hippocampal neurons.

The treatment of multidrug-resistant gram-negative bacterial infections has become a challenge in today's healthcare field,and time-to-event data analysis has shown significant value in clinical prognostic studies of critically ill patients.This study comprehensively reviewed the results of the application of time-to-event analysis in clinical studies of anti-multidrug-resistant gram-negative bacterial drugs,aiming to provide a scientific basis for the optimization of therapeutic strategies and prognostic assessment of multidrug-resistant gram-negative bacterial infections,and to promote the widespread application of time-to-event analysis methods in similar studies.

AIM:To observe the effect of dexme-detomidine(DEX)on cerebral ischemia and reperfu-sion(I/R)injury and investigate the possible mecha-nism of nuclear factor erythroid derived 2-like 2(Nrf2)mediated ferroptosis on hippocampal neu-rons.METHODS:The oxygen glucose deprivation/reoxygenation(OGD/R)model in rat primary cul-tured hippocampal neurons was simulated,DEX(50 μmol/L)and Nrf inhibitor BRU(100 nmol/L)were used to observe the changes of ROS levels by DHE fluorescence probe.The middle cerebral ar-tery occlusion model in male SD rats were estab-lished,the degree of neurological impairment was detected by Longa score,and cerebral infarct size was detected by TTC staining.The Fe2+concentra-tion and levels of oxidative stress related factors were detected,oxidative stress and ferroptosis re-lated protein expressions were detected by West-ern blot.RESULTS:The fluorescence intensity of DHE in OGD/R+Dex Group was lower than that in CON group,and the fluorescence intensity of DHE in OGD/R+DEX+BRU group was higher than that in OGD/R+Dex group.Compared with Sham group,the Longa score and cerebral infarct size in I/R group were significantly increased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were significantly decreased.MDA and Fe2+concentrations were in-creased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were decreased,and TFR1 protein expression was increased.Compared with I/R group,in DEX+I/R group,the Longa score and ce-rebral infarct size were decreased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were increased.MDA and Fe2+concentrations were decreased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were increased,and TFR1 protein expression was decreased.The Nrf2 inhibitor Bru reversed the role of DEX.CONCLUSION:DEX protects against ce-rebral I/R injury through activating Nrf2 signaling pathway and inhibiting ferroptosis in hippocampal neurons.

The treatment of multidrug-resistant gram-negative bacterial infections has become a challenge in today's healthcare field,and time-to-event data analysis has shown significant value in clinical prognostic studies of critically ill patients.This study comprehensively reviewed the results of the application of time-to-event analysis in clinical studies of anti-multidrug-resistant gram-negative bacterial drugs,aiming to provide a scientific basis for the optimization of therapeutic strategies and prognostic assessment of multidrug-resistant gram-negative bacterial infections,and to promote the widespread application of time-to-event analysis methods in similar studies.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

objectiveTo investigate the differences in clinical indices and lipid metabolism between the patients with nonalcoholic fatty liver disease （NAFLD） and healthy individuals in the overweight population. MethodsIn this study， body mass index （BMI）>23 kg/m² was defined as overweight. A total of 62 overweight patients with NAFLD who were admitted to Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to April 2021 were enrolled as overweight NAFLD group， and 50 overweight individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical information and blood biochemical parameters were recorded for all subjects. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze serum lipidomic profile， and principal component analysis and orthogonal partial least squares-discriminant analysis were used to perform the multivariate statistical analysis of lipidomic data. The chi-square test was used for comparison of categorical data between two groups， and the independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups. ResultsThe overweight NAFLD group had a significantly higher BMI than the overweight control group （Z=-2.365， P=0.018）. As for serological markers， compared with the overweight control group， the overweight NAFLD group had significantly higher levels of red blood cells， hemoglobin， hematocrit， uric acid， total protein， globulin， alkaline phosphatase， gamma-glutamyl transpeptidase， alanine aminotransferase， aspartate aminotransferase， cholinesterase， low-density lipoprotein， total cholesterol， triglyceride， apolipoprotein B， and blood glucose （all P<0.05）. The lipidomic analysis showed that there was a significant difference in lipid metabolism between the two groups， and a total of 493 differentially expressed lipids were identified （VIP value>1， P<0.05）， among which 143 lipids were significantly upregulated and 350 lipids were significantly downregulated in the overweight NAFLD group. The mean total fatty acid content in the overweight NAFLD group was 3.6 times that in the overweight control group. Compared with the overweight control group， the overweight NAFLD group had a significant reduction in the content of triglyceride with>3 unsaturated bonds （P<0.001） and a significant increase in the content of triglyceride with ≤3 unsaturated bonds （P<0.001）. ConclusionCompared with healthy overweight individuals， overweight NAFLD patients tend to have significant abnormalities in some biochemical parameters and lipid metabolites， with significant increases in the content of fatty acid in blood and the types of saturated fat chains in triglycerides.

Liver metastasis is a key factor impacting the treatment outcomes and survival prognoses of patients with colorectal cancer(CRC).In recent years,immunotherapy has demonstrated revolutionary potential in the treatment of a wide range of solid tumors by strengthen-ing the host's antitumor immune response and has become a mainstream option for the treatment of metastatic or recurrent solid tumors.Immune checkpoint inhibitor-based immunotherapy,in particular,has shown promising advances in safety and efficacy in CRC treatment,especially for deficient mismatch repair(dMMR)CRC.Despite these advances,patients with liver metastases have not seen any improvements in their survival prognoses.In this article,we comprehensively review immunotherapeutic strategies for treating liver metastases from CRC,discuss the efficacy of each strategy,and provide an in-depth discussion of prospective future directions.

Liver metastasis is a key factor impacting the treatment outcomes and survival prognoses of patients with colorectal cancer(CRC).In recent years,immunotherapy has demonstrated revolutionary potential in the treatment of a wide range of solid tumors by strengthen-ing the host's antitumor immune response and has become a mainstream option for the treatment of metastatic or recurrent solid tumors.Immune checkpoint inhibitor-based immunotherapy,in particular,has shown promising advances in safety and efficacy in CRC treatment,especially for deficient mismatch repair(dMMR)CRC.Despite these advances,patients with liver metastases have not seen any improvements in their survival prognoses.In this article,we comprehensively review immunotherapeutic strategies for treating liver metastases from CRC,discuss the efficacy of each strategy,and provide an in-depth discussion of prospective future directions.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.