Sepsis,characterized by inadequate host responses to infection,leads to life-threatening organ dysfunction and is a major cause of mortality among critically ill patients.Among them,immunosuppression plays a crucial role in the development of sepsis.This review elaborates on the pathogenesis and immunological features of sepsis-induced immunosuppression.Then,we analyzed the current situation of immunotherapy for sepsis from the angles of restoring immune stimulation,eliminating inflammatory mediators,and improving immunity.We emphasized the need for a comprehensive analysis of the traits and immunological types of patients with sepsis,generating new approaches to improve the prognosis of sepsis based on immune targets.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective:This study examined the development trend and research hotspot of cardiopulmonary brain resuscitation in the last ten years by a visual analysis of the literature on post-cardiac arrest brain injury.Methods:English articles were acquired from the Web of Sciences (WOS) core database. CiteSpace 5.8.R3 software was used to analyze annual publications, countries, institutions, authors. We identified the trending research areas by analyzing collaborative networks, keywords co-occurrence, burst detection analysis, timeline and time-zone diagrams.Results:The search included 10 867 articles in the WOS core database from Jan 1, 2013 to Oct 25, 2023. In the last ten years, the top 3 nations were the United States, China, and Japan, with the United States having the most citation of 3691 and an centrality of 0.47. The author with the highest number of publications was Hans Friberg from Sweden. The top 5 most frequent keywords in WOS were cardiac arrest, cardiopulmonary resuscitation, resuscitation, survival, outcome. Keyword cluster analysis showed 4 clusters, including: #0 of-hospital cardiac arrest, #1 traumatic brain injury, #2 targeted temperature management, #3 global cerebral ischemia. Keyword burst showed that the top 5 ranked by strength are mild hypothermia, emergency cardiovascular care, neuron specific enolase, cerebral ischemia, epinephrine, and the top 5 ranked by the year of burst begins are out-of-hospital cardiac arrest, cpr, epinephrine, coma, and task force. The timeline and time zone charts indicated that, starting in 2017, the main fields of study concentration were traumatic brain injury and out-of-hospital cardiac arrest. Additionally, extracorporeal membrane, intensive care, risk factors, and electroencephalography were identified as new high-frequency keywords.Conclusions:Over the past ten years, the research hotspots on post-cardiac arrest brain injury include out-of-hospital cardiac arrest, traumatic brain injury, and target temperature control. The research development trends will be extracorporeal membrane oxygenation, critical care, and EEG.

Objective:To evaluate the significance of the lumbar bowstring ratio (LBR) and sagittal spine-pelvis parameters in predicting postoperative neurogenic pain in adult patients with high-grade lumbar isthmic spondylolisthesis following spinal fusion surgery.Methods:A retrospective analysis was conducted on the clinical and imaging data of 95 adult patients with high-grade lumbar isthmic spondylolisthesis treated by spinal surgery at Xiangya Hospital of Central South University from August 2012 to January 2023. Each patient was followed for a minimum of six months. Participants were categorized into pain and non-pain groups based on the presence of persistent radicular pain (≥8 weeks) and a visual analogue scale (VAS) score of ≥3 postoperatively. The pain group comprised 15 patients (5 males, 10 females; mean age 55.47±6.42 years, range 46-71 years), while the non-pain group included 80 patients (20 males, 60 females; mean age 60.98±11.50 years, range 40-85 years). Clinical outcomes were assessed using the Oswestry Disability Index (ODI) and VAS scores. LBR was defined as the ratio of the vertical distance from the anterior convexity of the L 1-L 5 anterior longitudinal ligament to a line connecting the posterior superior margin of the L1 vertebra and the posterior margin of the S1 vertebra, to the distance between these two points. Spinal-pelvic parameters measured included pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), PT/SS ratio, and changes in LBR before and after surgery (ΔLBR). Statistical comparisons of demographic and imaging parameters were performed between the two groups, and variables showing significant differences were subjected to binary logistic regression analysis to identify independent risk factors for postoperative neurogenic pain. Results:All 95 patients achieved complete anatomical reduction of the dislocation without reported wound infections. Follow-up was completed at 7.68±2.98 months (range 6-12 months) postoperatively. Among the patients, 15 developed iatrogenic radicular pain. Postoperative complications included pulmonary infection (4 cases: 1 in the pain group, 3 in the non-pain group), cerebrospinal fluid leakage (8 cases: 2 in the pain group, 6 in the non-pain group), and delirium (5 cases: 2 in the pain group, 3 in the non-pain group). No significant differences were observed in demographic data between the groups ( P>0.05). Both groups demonstrated significant improvements in ODI (pain group Z=-3.413, P=0.001; non-pain group Z=-7.772, P<0.001) and VAS scores (pain group Z=-3.426, P=0.001; non-pain group Z=-7.838, P<0.001) at the 6-month follow-up compared to preoperative values. Significant differences were found between the pain and non-pain groups in PI ( t=3.315, P=0.004), PT ( t=5.087, P<0.001), SS ( t=7.431, P<0.001), LL ( t=3.764, P<0.001), PT/SS ( t=7.267, P<0.001), LBR ( t=6.455, P<0.001), and ΔLBR ( Z=5.362, P<0.001) before and after surgery. Binary logistic regression analysis identified smaller preoperative PT/SS [ OR=0.760, 95% CI(0.601, 0.961), P=0.022] and larger preoperative LBR [ OR=5.721, 95% CI (1.068, 30.634), P=0.042] as independent risk factors for postoperative neurogenic pain. Conclusion:High LBR and reduced PT/SS are significant risk factors for neurogenic pain following complete discectomy and fusion in adult patients with high-grade lumbar isthmic spondylolisthesis. For such patients, careful consideration is warranted regarding anatomical complete reduction during surgical intervention.

Humans ; Critical Illness ; Critical Care ; Intensive Care Units ; Surveys and Questionnaires

Papaya, which is mainly cultivated in the southeastern region of China, is one of the four famous fruits in Lingnan. It is favored by people because of its edible and medicinal value. Fructose-6-phosphate, 2-kinase/fructose-2, 6-bisphosphatase (F2KP) is a unique bifunctional enzyme with a kinase domain and an esterase domain that catalyzes the synthesis and degradation of fructose-2, 6-bisphosphate (Fru-2, 6-P₂), an important regulator of glucose metabolism in organisms. In order to study the function of the gene CpF2KP encoding the enzyme in papaya, it is particularly important to obtain the target protein. In this study, the coding sequence (CDS) of CpF2KP, with a full-length of 2 274 bp, was got from the papaya genome. The amplified sequence of full-length CDS was cloned into the vector PGEX-4T-1 which was double digested with EcoR I and BamH I. The amplified sequence was constructed into a prokaryotic expression vector by genetic recombination. After exploring the induction conditions, the results of SDS-PAGE showed that the size of the recombinant GST-CpF2KP protein was about 110 kDa. The optimum IPTG concentration and temperature for CpF2KP induction were 0.5 mmol/L and 28 ℃, respectively. The purified sin[A1] gle target protein was obtained after purifying the induced CpF2KP protein. In addition, the expression level of this gene was detected in different tissues, and showed that the gene was expressed at the highest level in seeds and the lowest in pulp. This study provides an important basis for further revealing the function of CpF2KP protein and studying the involved biological processes of this gene in papaya.
Humans ; Carica/genetics* ; Recombinant Proteins ; Carbohydrate Metabolism ; Cloning, Molecular ; China

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d,l-choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d,l-choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14 (Cxcl14) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.

Objective To investigate the value of high density lipoprotein-cholesterol (HDL-C) in the diagnosis and risk assessment of non-alcoholic fatty liver disease (NAFLD).Methods A cross-sectional study and multistage stratified random sampling method were performed in epidemiological survey.According to inclusion and exclusion criteria,a total of 3 312 individuals were enrolled and divided into NAFLD group (913 cases) and non-NAFLD group (2 399 cases).The serum lipid levels were compared between the two groups.Receiver operating characteristic (ROC) curve was performed to evaluate the value of HDL-C in the diagnosis of NAFLD.The binary logistic regression models were established based on HDL-C level.The differences in liver function indexes were compared among the research objects with different HDL-C levels.T test and MannWhitney U test were performed for statistical analysis.Results The serum levels of total cholesterol,triglyceride and low density lipoprotein-cholesterol (LDL-C) of NAFLD group were all higher than those of non-NAFLD group ((5.24 ±0.92) mmol/L vs.(4.98 ±0.92) mmol/L,(1.95 ± 1.41) mmol/L vs.(1.13 ± 0.68) mmol/L,(3.31 ± 0.84) mmol/L vs.(3.09 ± 0.84) mmol/L),and the differences were statistically significant (t =-7.29,-22.38 and-6.84,all P ＜ 0.01).However the serum HDL-C level of NAFLD group was lower than that of non-NAFLD group((1.30 ±0.33) mmol/L vs.(1.64 ±0.40) mmol/L),and the difference was statistically significant (t =24.93,P ＜0.01).The incidence of hypercholesterolemia,hypertriglyceridemia,hypo-high-density lipoprotein cholesterolemia and hyper-low-density lipoprotein cholesterolemia of NAFLD group was 48.0％ (438/913),44.8％ (409/913),31.0％ (283/913) and 82.8％ (756/913),respectively,which were significantly higher than that of non-NAFLD group (36.8％,882/2 399;13.2％,317/2 399;10.5％,251/2 399;71.8％,1 723/2 399),and the differences were statistically significant (x2 =34.65,385.43,206.18 and 42.37,all P ＜ 0.01).Using the cut-off values of HDL-C ≤ 1.66 mmol/L in female and ≤ 1.33 mmol/L in male,the area under curve (AUC) values for NAFLD diagnosis were 0.720 (95％ confidence interval (CI) 0.693 to 0.747) and 0.708 (95％ CI 0.679 to 0.737),respectively,the sensitivity was 79.1％ and 76.6％,and the specificity was 55.0％ and 54.6％.The results of binary logistic regression models based on HDL-C level indicated that prevalence of NAFLD in female with low HDL-C was 4.584 times (95％ CI 3.530 to 5.940,P ＜0.01) higher than that in female with high HDL-C;the prevalence of NAFLD in male with low HDL-C was 3.898 times (95％ CI 3.020 to 5.030,P ＜0.01) higher than that of male with high HDL-C.The alanine aminotransferase (ALT),aspartate transaminase (AST),gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) levels of low HDL-C group were all higher than those of high HDL-C group (20.10 U/L,14.40 U/L to 29.40 U/L vs.16.80 U/L,12.70 U/L to 23.00U/L;19.20 U/L,16.00 U/Lto23.70 U/Lvs.19.00 U/L,16.00 U/Lto22.17 U/L;22.00 U/L,14.00 U/L to34.00 U/L vs.15.00 U/L,11.00 U/L to 23.00 U/L and 71.00 U/L,59.00 U/L to 85.00 U/L vs.66.00 U/L,55.00 U/L to 82.00 U/L),and the differences were statistically significant (Z =-10.53,-2.20,-14.19 and-5.87,all P＜0.05).Conclusion The serum HDL-C level is negatively correlated with the risk of NAFLD level,and the NAFLD risk of individuals with low HDL-C level is significantly higher than individuals with high HDL-C level.