OBJECTIVE: To explore the correlation between albumin (Alb) combined with diuretic treatment and the mortality risk of septic patients with pre-existing congestive heart failure based on the United States Critical Care Medical Information Database-IV (MIMIC-IV), and to conduct the external validation. METHODS: A retrospective cohort study was conducted. The clinical data of septic patients with pre-existing congestive heart failure admitted to the intensive care unit (ICU) from 2008 to 2019 in the MIMIC-IV 2.0 were extracted, including demographic characteristics, comorbidities, laboratory indicators on the first day of ICU admission, severity of illness, treatment measures, etc. For external validation, clinical data were collected from septic patients with pre-existing congestive heart failure admitted to the ICU of the Second People's Hospital of Shenzhen from October 2022 to December 2023. The patients were divided into Alb alone group and Alb combined with diuretic group. The ICU mortality was defined as the primary outcome event, and the 30-day and 60-day mortality were defined as the secondary outcomes. Multivariate Cox proportional hazard regression analysis was conducted to investigate the relationship between Alb combined with diuretic treatment and the mortality risk of ICU and 30 days in septic patients with pre-existing congestive heart failure, and subgroup analysis was performed. Kaplan-Meier survival curve was plotted to compared the 60-day cumulative survival rate between the Alb alone group and Alb combined with diuretic group. RESULTS: (1) Analysis results of data from MIMIC-IV: a total 1 754 patients were enrolled, of which 378 in the Alb alone group, and 1 376 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients in the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.11% (263/1 376) vs. 30.42% (115/378), 30-day mortality: 18.90% (260/1 376) vs. 32.54% (123/378), 60-day mortality: 24.49% (337/1 376) vs. 39.15% (148/378), all P < 0.05]. Based on the multivariate Cox proportional hazard regression adjusted models considering demographic characteristics, comorbidities, laboratory indicators, severity of illness, and treatment measures, it was shown that the use of Alb combined with diuretic was significantly associated with a reduced risk death of ICU and 30 days [ICU mortality risk: hazard ratio (HR) = 0.597, 95% confidence interval (95%CI) was 0.460-0.774, P < 0.001; 30-day mortality risk: HR = 0.557, 95%CI was 0.433-0.716, P < 0.001]. Subgroup analysis revealed that after adjusting for variables, regardless of gender, age, and whether or not patients had comorbidities such as hypertension, diabetes, severe liver disease, acute renal insufficiency, and sequential organ failure assessment (SOFA) score, the ICU mortality risk was significantly reduced in patients treated with Alb combined with diuretic (all HR < 1, P < 0.05), with no interaction observed (all P > 0.05). Kaplan-Meier survival curve showed the 60-day cumulative survival rate of patients in the Alb combined with diuretic group was significantly higher than that in the Alb alone group (Log-rank test: χ ² = 49.62, P < 0.05). (2) External validation: a total of 385 patients were enrolled, of which 144 in the Alb alone group, and 241 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients of the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.92% (48/241) vs. 31.25% (45/144), 30-day mortality: 19.09% (46/241) vs. 28.47% (41/144), 60-day mortality: 24.07% (58/241) vs. 34.03% (49/144), all P < 0.05]. The results of multivariate Cox proportional hazard regression analysis, subgroup analysis, and Kaplan-Meier survival curve analysis were consistent with the data analysis of the MIMIC-IV database. CONCLUSIONS Combination therapy of Alb and diuretic was associated with reduced mortality risk in septic patients with pre-existing congestive heart failure.
Humans ; Heart Failure/mortality* ; Retrospective Studies ; Sepsis/drug therapy* ; Intensive Care Units ; Diuretics/therapeutic use* ; Male ; Female ; Aged ; Middle Aged ; Proportional Hazards Models ; Hospital Mortality

Objective:To explore the difference of inflammatory factor imbalance between adolescent and adult patients with depression.Methods:A total of 30 adolescent and 30 adult patients with depression, and 30 adolescent and 30 adult healthy controls were included from January 2022 to August 2023. Interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-beta1(TGF-β1), interleukin-10(IL-10) and Maresin-1(MaR1) level were detected by enzyme-linked immunosorbent assay. 24-item Hamilton depression scale (HAMD-24) was used to assess the severity of depression in all depressed patients. SPSS 26.0 statistical software was used for t-test, covariance analysis, Spearman analysis and multivariate binary logistic regression, and the predictive value of selected inflammatory factors in depression was evaluated by receiver operating characteristic(ROC) curve. Results:(1)In adolescent group, the levels of IL-6 ((64.000±38.632) pg/mL), IL-17((239.132±49.757) pg/mL), and TGF-β1((737.267±328.447)pg/mL) in patients with depression were higher than those in control group((32.396±16.330)pg/mL, (214.954±42.326)pg/mL, (454.542±297.194)pg/mL, all P<0.05), while the level of MaR1((21 381.301±3 946.011)pg/mL) was significantly lower than that in control group((30 130.138±10 278.999)pg/mL)( P<0.001). The level of IL-17 was positively correlated with the total score of HAMD-24 ( r=0.429) and the course of disease ( r=0.571), the level of IL-10 was negatively correlated with body weight factor score ( r=-0.384), and the levels of TGF-β1 was negatively correlated with anxiety/somatization factor score ( r=-0.449)(all P<0.05) in adolescent patients with depression.MaR1( B=0.000 1, OR=0.999 8, AUC=0.794, P<0.05) was an independent risk factor for adolescents depression.(2)In adult depression group, the levels of IL-6, IL-17, IL-10, TGF-β1 and MaR1 were higher than those in adult control group(all P<0.05). The level of TGF-β1 in adult depression group was negatively correlated with the total score of HAMD-24 ( r=-0.427), the score of anxiety/somatization factor ( r=-0.368), the score of blocking factor ( r=-0.405), and the score of hopelessness factor ( r=-0.398).The level of MaR1 was positively correlated with the age of onset of disease ( r=0.425)(all P<0.05) in adult patients with depression.MaR1( B=0.000 4, OR=1.000 3, AUC=0.874, P<0.001) and IL-6( B=0.040, OR=1.040 7, AUC=0.779, P<0.05) were independent risk factors for adult depression.The AUC of IL-6 combined with MaR1 was 0.938. Conclusion:There are differences in the underlying mechanism of immune imbalance between adolescent and adult patients with depression.MaR1 may be a diagnostic biomarker for depression in adolescents and adults.

Objective:To study the regional distribution, temporal trend, and health inequity of burn incidence in the world from 1990 to 2019.Methods:The data related to burns worldwide from 1990 to 2019 were collected from the database of Global Burden of Disease (GBD). Based on the number of burn cases and age-standardized incidence rates, the incidence of burn was observed by age, region, socio-demographic index (SDI) area (divided into 5 categories of SDI areas: high, medium-high, medium, medium-low and low, the higher the area, the higher the degree of social development) and country, all of which were expressed as estimated values. Joinpoint regression analysis of the age-standardized incidence of burns from 1990 to 2019 was performed using Joinpoint 4.8.0.1 software to observe the average annual percentage change (AAPC). Rstudio software was used to analyze the Spearman correlation between the age-standardized incidence of burns and SDI from 1990 to 2019. The global inequities of burn incidence were evaluated using the slope index and concentration index from the health equity assessment toolkit, where the slope index reflected the absolute difference in burn incidence between countries with the lowest and highest SDI, and the concentration index indicated the degree to which burn incidence was concentrated in countries with low or high SDI.Results:From 1990 to 2019, the number of global burncases increased from 8 378 121.71 to 8 955 227.68, with an increase of 6.89%. However, the age-standardized incidence rate of burns showed an overall downward trend, from 149.86/100 000 in 1990 to 117.51/100 000 in 2019, with an AAPC of -0.80%. The incidence of burns in the population aged 10-19 years ranked the first in all age groups during the 30 years. Among the six regions of the world, the number of burn cases and the age-standardized incidence rate of burn in the Americas were the highest in 2019, but these two indexes were lower than those in 1999. In 2019, the number of burn patients in medium SDI areas was the highest, and the number of burn patients in low SDI areas was the lowest. The age-standardized incidence of burns was the highest in high SDI areas, and the lowest in medium-low SDI areas. From 1990 to 2019, the number of patients in high and medium-high SDI areas decreased, and the number of patients in other SDI areas increased. Compared with 1990, the age-standardized incidence rates of burns decreased in all SDI regions in 2019, with the greatest decline seen in high SDI and medium-high SDI regions. Cuba had the highest standardized incidence of burns, while Pakistan had the lowest. Spearman correlation analysis showed that from 1990 to 2019, the age-standardized incidence rates of burns in 204 countries and regions were positively correlated with SDI (all P<0.05), and the correlation coefficient decreased from 0.49 in 1990 to 0.37 in 2019. The health inequality slope index decreased from 212.90/100 000 in 1990 to 59.12/100 000 in 2019, and the concentration index decreased from 21.77% in 1990 to 8.38% in 2019. Conclusion:From 1990 to 2019, the global burn incidence rates are disproportionately concentrated in countries and regions with better development status. A significant reduction in the global burn incidence has been accompanied by a significant reduction in these inequities.

Objective:To study the regional distribution, temporal trend, and health inequity of burn incidence in the world from 1990 to 2019.Methods:The data related to burns worldwide from 1990 to 2019 were collected from the database of Global Burden of Disease (GBD). Based on the number of burn cases and age-standardized incidence rates, the incidence of burn was observed by age, region, socio-demographic index (SDI) area (divided into 5 categories of SDI areas: high, medium-high, medium, medium-low and low, the higher the area, the higher the degree of social development) and country, all of which were expressed as estimated values. Joinpoint regression analysis of the age-standardized incidence of burns from 1990 to 2019 was performed using Joinpoint 4.8.0.1 software to observe the average annual percentage change (AAPC). Rstudio software was used to analyze the Spearman correlation between the age-standardized incidence of burns and SDI from 1990 to 2019. The global inequities of burn incidence were evaluated using the slope index and concentration index from the health equity assessment toolkit, where the slope index reflected the absolute difference in burn incidence between countries with the lowest and highest SDI, and the concentration index indicated the degree to which burn incidence was concentrated in countries with low or high SDI.Results:From 1990 to 2019, the number of global burncases increased from 8 378 121.71 to 8 955 227.68, with an increase of 6.89%. However, the age-standardized incidence rate of burns showed an overall downward trend, from 149.86/100 000 in 1990 to 117.51/100 000 in 2019, with an AAPC of -0.80%. The incidence of burns in the population aged 10-19 years ranked the first in all age groups during the 30 years. Among the six regions of the world, the number of burn cases and the age-standardized incidence rate of burn in the Americas were the highest in 2019, but these two indexes were lower than those in 1999. In 2019, the number of burn patients in medium SDI areas was the highest, and the number of burn patients in low SDI areas was the lowest. The age-standardized incidence of burns was the highest in high SDI areas, and the lowest in medium-low SDI areas. From 1990 to 2019, the number of patients in high and medium-high SDI areas decreased, and the number of patients in other SDI areas increased. Compared with 1990, the age-standardized incidence rates of burns decreased in all SDI regions in 2019, with the greatest decline seen in high SDI and medium-high SDI regions. Cuba had the highest standardized incidence of burns, while Pakistan had the lowest. Spearman correlation analysis showed that from 1990 to 2019, the age-standardized incidence rates of burns in 204 countries and regions were positively correlated with SDI (all P<0.05), and the correlation coefficient decreased from 0.49 in 1990 to 0.37 in 2019. The health inequality slope index decreased from 212.90/100 000 in 1990 to 59.12/100 000 in 2019, and the concentration index decreased from 21.77% in 1990 to 8.38% in 2019. Conclusion:From 1990 to 2019, the global burn incidence rates are disproportionately concentrated in countries and regions with better development status. A significant reduction in the global burn incidence has been accompanied by a significant reduction in these inequities.

Objective To investigate the intervention effects and mechanism of icariin on prostate cancer based on network pharmacology and animal experiments.Methods The targets of icariin were predicted using the SwissTargetPrediction database.Protein-protein interaction networks were constructed with the String database,and core targets were screened using Cytoscape 3.9.1.GO and KEGG enrichment analysis on core targets were conducted with the Metascape database to predict the mechanism of action.A PC-3 tumor-bearing mouse model of prostate cancer was established to observe the inhibitory effects of icariin alone and in combination with paclitaxel on tumor growth.Results Network pharmacology predictions suggested that icariin has potential therapeutic effects on prostate cancer,with core targets potentially including serine/threonine kinase 1(AKT1),B-cell lymphoma-2(BCL2),epidermal growth factor receptor(EGFR),heat shock protein 90 alpha family class A member 1(HSP90AA1),heat shock protein 90 alpha family class B member 1(HSP90AB1),nuclear factor kappa B subunit 1(NF-κB1),tumor protein p53,etc.Animal experiments found that compared with the model control group,the tumor volume growth in the icariin group and the paclitaxel group was significantly inhibited,and the serum tumor necrosis factor content was significantly reduced,while testosterone levels did not change significantly.Both groups significantly downregulated the mRNA expression of Notch1,Jagged1 and Hes1(P<0.05),with the combined treatment group showing a more significant inhibitory effect.Conclusions Both network pharmacology and animal experimental results confirmed that icariin has a significant inhibitory effect on prostate cancer.One of the mechanisms of its anti-tumor effects may be the significant inhibition of the activated Notch signaling pathway in tumors.

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.
Glycolysis ; Colonic Neoplasms/metabolism* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Phosphopyruvate Hydratase/metabolism* ; Flavanones/pharmacology* ; Cell Line, Tumor ; Databases, Genetic ; Cell Proliferation/drug effects* ; Transfection ; Warburg Effect, Oncologic

Vascular endothelial growth factor (VEGF) is the main regulator of physiological angiogenesis during embryonic development, bone growth, and reproductive function, and it also participates in a series of pathological changes. Traditional Chinese medicine (TCM), with a history of more than 2000 years, has been widely used in clinical practice, while the exploration of its mechanisms has only begun. This review summarizes the research of recent years on the influence of TCM on VEGF. It is found that many Chinese medicines and recipes have a regulatory effect on VEGF, indicating that Chinese medicine has broad prospects as a complementary and alternative therapy, providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Vascular Endothelial Growth Factor A

Objective:Charcot-Marie-Tooth disease (CMT) comprises a group of clinically and genetically heterogeneous inherited neuropathies with an estimated prevalence of 1 in 2500. This study aimed to analyze the clinical and mutational characteristics of Chinese CMT patients with MFN2, BSCL2 and LRSAM1 variants.Methods:In this study, genetic analysis was performed in 206 Chinese patients at Chinese PLA General Hospital from December 2012 to March 2020 with clinical diagnosis of CMT, and reported variants of MFN2, BSCL2 and LRSAM1 related to CMT2.Results:We reported ten MFN2 mutations in ten unrelated patients (7 male, 3 female), two of whom had positive family history. Three novel mutations were detected including c.475-2A>G (splicing); c.687dupA (p.E230Rfs*16) and c.558dupT (p.S186fs). We reported three BSCL2 mutations of four unrelated patients, including c.461C>G (p.S154W), c.461C>T(p.S154L), and novel variants of c.1309G>C (p.A437P) and c.845C>T (p.A282V). Furthermore, two novel variants of LRSAM1, including c.1930G>T (p.G644C) and c.1178T>A (p.L393Q) were detected in two unrelated patients.Conclusion:Mutational spectrum of MFN2-, BSCL2-and LRSAM1-related CMT disease is expanded with the identification of novel variants in Chinese patients.

Objective To evaluate the feasibility and safety of tracheal extubation in operating room for patients with end-stage chronic obstructive pulmonary disease (COPD) after single-lung transplantation. Methods Clinical data of 57 recipients who underwent single-lung transplantation due to end-stage COPD were retrospectively analyzed. According to the evaluation indexes of tracheal extubation in operating room established by our hospital, 17 recipients eligible for tracheal extubation in operating room were assigned into the operating room extubation group (OR extubation group) and 40 recipients receiving tracheal extubation in intensive care unit (ICU) were allocated in the ICU extubation group. The evaluation results of intraoperative tracheal extubation and postoperative recovery were compared between two groups. Results Compared with the ICU extubation group, recipients in the OR extubation group had higher oxygenation index, lower arterial partial pressure of carbon dioxide (PaCO₂), lower blood lactic acid level, less fluctuation range of blood pressure and fewer cases receiving extracorporeal membrane oxygenation (ECMO) during operation (all P < 0.05). Two recipients in the OR extubation group received repeated tracheal intubation at 6 and 8 h after returning to ICU, and tracheal extubation at postoperative 6 and 9 d. In the OR extubation group, time of postoperative mechanical ventilation, length of postoperative ICU and hospital stay of the recipients were shorter than those in the ICU extubation group (all P < 0.05). The incidence of grade 3 primary graft dysfunction (PGD), atrial tachyarrhythmia, continuous renal replacement therapy and 1-year survival rate did not significantly differ between two groups (all P > 0.05). Conclusions The tracheal extubation regimen in the operating room for COPD patients after single-lung transplantation established by our hospital is safe and feasible, which shortens the time of postoperative mechanical ventilation, the length of postoperative ICU and hospital stay, whereas does not increase the incidence of postoperative complications.

Objective:To investigate the features and advantages of ambulatory blood pressure monitoring (ABPM) applied in children with kidney diseases as well as the correlation between ambulatory blood pressure and clinical indicators.Methods:The clinical data of children with kidney diseases who were hospitalized and received ABPM in Children′s Hospital Affiliated to Capital Institute of Pediatrics from March 2012 to March 2018 were collected.Clinical blood pressure and ABPM indicators were analyzed and compared between different clinical groups.Results:(1) Among 170 cases enrolled, 69 cases (40.6%) were hypertension by measuring clinical blood pressure, 54 cases (31.8%) were ambulatory hypertension, 43 cases (25.3%) of whom had severe ambulatory hypertension, 17 cases (10.0%) had white coat hypertension, 41 cases (24.1%) were defined as masked hypertension, and 139 cases (81.8%) had impaired circadian rhythm of blood pressure.(2) Ninety-five point nine percent (163/170 cases) were detected of abnormal blood pressure by ABPM, and the rate was significantly higher than that detected by clinical blood pressure (40.6%, 69/170 cases) ( χ2=149.176, P<0.001). In the 40 cases who were administrated with antihypertensive drugs, 95.0%(38 cases) were detected to have anomalous blood pressure by ABPM, significantly more than that detected by clinical blood pressure(42.5%, 17/40 cases)( χ2=10.208, P=0.001). (3) Logistic regression analysis indicated that a prolonged clinical course of more than 3 months, obesity and nephrotic-range proteinuria were the risk factors of ambulatory hypertension, and the odd ratios were 5.345, 3.530 and 6.560, respectively.Circadian rhythm disorders of blood pressure were more common in the children with abnormal renal function than in those with normal renal function[89.7%(52/58 cases) vs.75.9%(85/112 cases)], and the difference was statistically significant ( χ2=4.626, P=0.031). Conclusions:Children with kidney diseases have a high incidence of hypertension.ABPM plays a key role in detecting hypertension and recognizing white coat hypertension.Nephrotic-range proteinuria and obesity are risk factors for ambulance hypertension, and abnormal renal function is associated with nocturnal blood pressure disorders.