摘要:ObjectiveTo investigate the role of the neutrophil-to-lymphocyte ratio (NLR) in predicting the in-hospital mortality risk of patients with acute aortic dissection (AAD) in multicenter hospitals.MethodsA multicenter retrospective cohort study was conducted. Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals: Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital, the Third Affiliated Hospital of Xinxiang Medical University, and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021. According to the quartiles of serum NLR levels, the patients were divided into four groups: first quartile (Q1, n=660), second quartile (Q2, n=661), third quartile (Q3, n=661), and fourth quartile (Q4, n=660). The clinical characteristics and biochemical indicators of each group were compared. Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters. Restricted cubic splines, Kaplan-Meier survival analysis, and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.ResultsThe median age of all patients was 54 [interquartile range (IQR): 46-63] years, including 2096 males and 546 females. Compared with Q1-Q3 groups, patients in Q4 group had a lower incidence of smoking history and diabetes history, and were more likely to have DeBakey type Ⅰ AAD (P<0.05). Additionally, the levels of aspartate aminotransferase, high-density lipoprotein cholesterol, creatinine, and D-dimer in Q4 group were higher, while the levels of triglycerides and C-reactive protein (CRP) were lower (P<0.01). The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer (r=0.43, P<0.01) and creatinine (r=0.16, P<0.01). The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients (P<0.01). Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups (P<0.0001). Furthermore, multivariate Cox regression analysis demonstrated that compared with Q1 group, the hazard ratio (HR) of NLR in Q4 group was 1.77(95%CI 1.33-2.37, P<0.001), which was an independent risk factor for the primary endpoint events.ConclusionA higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients, and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.
摘要:ObjectiveTo investigate the potential association between methylation levels of CpG locus of brain-derived neurotrophic factor (BDNF) gene and risk of acute stress disorder (ASD) [post-traumatic stress disorder (PTSD) or post-traumatic depression].Methods(1) 30 specific pathogen-free (SPF)-grade male ICR mice were randomly divided into control group, 24 h restraint stress (Res) group, and Res+5-Aza-2'deoxycytidine (Res+5-Aza-cdR) group, with 10 mice in each group. An ASD mouse model was established using 24h restraint stress. The body weight of the mice was recorded daily. At 24 h and 48 h after the successful establishment of the model, open field tests were conducted to evaluate locomotor activity level and anxiety-like behavior of the mice. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect BDNF mRNA and protein expression levels in the hippocampus of mice in each group. (2) Relevant genome-wide association study (GWAS) summary data were utilized for instrumental variable (IV) selection. A two-sample Mendelian randomization (TSMR) approach was applied to analyze the causal relationship between CpG site methylation of BDNF gene and ASD risk. The leave-one-out method was used to verify the results.Results(1) The results of body weight monitoring and the open field test showed that compared with control group, the body weight, the residence time in the central area, the total movement distance, and the activity times of mice in Res group were significantly decreased (P<0.001). Compared with Res group, the body weight, the residence time in the central area, the total movement distance and activity times of mice in Res+5-Aza group were significantly increased (P<0.001). The results of RT-qPCR and Western blotting showed that compared with control group, the expression levels of BDNF mRNA and protein in the hippocampus of the mice in Res group were significantly decreased (P<0.05). Compared with Res group, the expression level of BDNF mRNA and protein in Res+5-Aza group was significantly higher (P<0.001). (2) TSMR analysis results showed that the cg10635145 site in BDNF gene (OR=0.862, 95%CI 0.793-0.938, P=0.043) was negatively correlated with the risk of PTSD. The cg08362738 site (OR=0.975, 95%CI 0.960-0.992, P=0.003) was negatively correlated with the risk of trauma-related depression, whereas the cg18117895 site (OR=1.008, 95%CI 1.000-1.016, P=0.047) was positively correlated with the risk of trauma-related depression. The results of Leave-one-out test showed that the causal relationship between the single nucleotide polymorphism (SNP) of CpG site in BDNF gene and ASD was not affected by a strong Ⅳ.ConclusionThe CpG loci cg1063145 and cg08362738 of BDNF gene may be protective factors for ASD-related diseases, while cg18117895 may be a risk factor.
摘要:ObjectiveTo explore the risk factors for 28-day mortality of sepsis-associated acute kidney injury (SA-AKI) patients and to develop a nomogram risk prediction model.MethodsA retrospective cohort study was conducted, involving 184 patients with SA-AKI admitted to the intensive care unit (ICU) of the 940th Hospital of Joint Logistic Support Force of PLA between January 2017 and December 2022. Patients were categorized into survival (n=135) and non-survival (n=49) groups based on 28-day mortality. Clinical data were collected, and statistically significant risk factors were preliminarily screened. Multivariate stepwise logistic regression analysis was performed to identify independent risk factors for 28-day mortality of SA-AKI patients. A nomogram predictive model was constructed using these factors, and internally validated with the Bootstrap method. The receiver operating characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the predictive value and accuracy of the model.ResultsThe 28-day mortality rate among 184 SA-AKI patients was 26.6% (49/184). Multivariate stepwise logistic regression analysis identified multiple organ dysfunction syndrome (MODS) (OR=16.393, 95%CI 4.317-62.254, P<0.001), high acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score (OR=1.097, 95%CI 1.036-1.161, P=0.002), low oxygenation index (OR=0.992, 95%CI 0.986-0.998, P=0.015), low neutrophil count (OR=0.912, 95%CI 0.860-0.968, P=0.002) and low fibrinogen concentration (OR=0.733, 95%CI 0.549-0.978, P=0.034) as independent risk factors. The prediction model equation was , logit(P)=-1.626+2.797×MODS+0.092×APACHE Ⅱ+(-0.311)×fibrinogen+(-0.092)×neutrophil count+(-0.008)×oxygenation index. Internal validation with 1000 Bootstrap resamples showed high consistency between predicted and actual values. ROC analysis showed an AUC of 0.911(95%CI 0.868-0.955, P<0.05) for the model, with 93.9% sensitivity and 78.5% specificity at a cut-off of 0.194. The Hosmer-Lemeshow test confirmed good calibration (P=0.62), and decision-making curve analysis demonstrated clinical utility within the high-risk threshold range (0.1-0.9).ConclusionsMODS, high APACHE Ⅱ score, low oxygenation index, low neutrophil count, and low fibrinogen concentration are independent risk factors for 28-day mortality in SA-AKI patients. The developed nomogram risk prediction model may provide important guidance for predicting 28-day mortality in SA-AKI patients.
摘要:ObjectiveTo analyze the predictive value of the serum amyloid A/C-reactive protein ratio (SAA/CRP), lactate dehydrogenase (LDH), and chitinase-40 (YKL-40) combined with conventional influencing factors for the prognosis of children with refractory mycoplasmal pneumonia (RMPP).MethodsA retrospective study was conducted on 180 children with RMPP admitted to the First People's Hospital of Nanyang from January to December 2023, serving as study group, and 90 children with general mycoplasmal pneumonia (GMPP) as control group. The clinical data of the two groups, including age, gender, and serum levels of SAA/CRP, LDH, and YKL-40, were compared. On the day of admission, the disease severity of the children in study group was assessed and divided into mild (n=102) and severe (n=78) groups. After treatment, they were further categorized into poor prognosis (n=52) and good prognosis (n=128) groups based on the occurrence of adverse events. The levels of serum SAA/CRP, LDH, and YKL-40 were compared between mild-case and severe-case children in study group, as well as between children with good and poor prognosis. A binary logistic regression model was used to analyze the influencing factors for poor prognosis in children with RMPP. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum SAA/CRP, LDH, and YKL-40 for the prognosis of children with RMPP. Conventional influencing factors [disease severity, oxygen therapy duration, pneumonia severity index (PSI) score, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score] were used as the conventional prediction scheme, and the conventional prediction scheme combined with the levels of serum SAA/CRP, LDH, and YKL-40 was used as the new prediction scheme. The predictive values of the two prediction schemes for the prognosis of children with RMPP were compared.ResultsThe levels of serum SAA/CRP, LDH, and YKL-40 in study group were higher than those in control group (P<0.05), and the levels of serum SAA/CRP, LDH, and YKL-40 in children with severe RMPP were higher than those in children with mild RMPP (P<0.05). In study group, the proportion of children with pleural effusion, the proportion of severe-case disease severity, oxygen therapy duration, PSI score, APACHE Ⅱ score, and the levels of serum SAA/CRP, LDH, and YKL-40 in children with poor prognosis were higher than those in children with good prognosis (P<0.05). Binary logistic regression analysis showed that disease severity, oxygen therapy duration, PSI score, APACHE Ⅱ score, and the levels of serum SAA/CRP, LDH, and YKL-40 were all factors affecting poor prognosis in children with RMPP (P<0.05). The areas under the curves (AUCs) of serum SAA/CRP, LDH, and YKL-40 for predicting the prognosis of children with RMPP were 0.756, 0.749, and 0.734, respectively. The AUC of the new prediction scheme was 0.945, which was significantly higher than that of the conventional prediction scheme (AUC=0.859), with a statistically significant difference (P=0.011).ConclusionSerum SAA/CRP, LDH, and YKL-40 levels combined with the conventional prediction scheme have a high predictive efficacy for the prognosis of children with RMPP.
关键词:refractory mycoplasma pneumoniae pneumonia;serum amyloid A/C-reactive protein ratio;lactate dehydrogenase;chitin enzymes protein 40
摘要:ObjectiveTo establish and evaluate a nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer.MethodsA retrospective study was conducted on 1298 patients with HBV-related primary liver cancer hospitalized in the Kunming Third People's Hospital from January 2012 to December 2022. General data and serological indicators were collected, and patients were divided into infection group (n=262) and control group (n=1036) based on the occurrence of spontaneous peritonitis. Univariate and LASSO regression analyses were used to screen variables, followed by binary logistic regression to analyze the influencing factors of spontaneous peritonitis in HBV-related primary liver cancer patients, leading to the establishment of a nomogram prediction model. Finally, the Hosmer-lemeshow (H-L) goodness of fit test, receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the fit degree, accuracy, calibration, and clinical practicability of the nomogram prediction model.ResultsSingle factor analysis revealed significant differences between infection group and control group in portal vein cancer thrombus (PVTT), Child-Pugh grade, China Liver Cancer Staging (CNLC) stage, alcohol consumption history, smoking history, white blood cell count (WBC), neutrophil count (NE), hemoglobin (Hb), fibrinogen (FIB), abnormal prothrombin (PIVKA-Ⅱ), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (TP), prealbumin (PA), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), cholinesterase (CHE), total bile acid (TBA), total cholesterol (TC), low density lipoprotein (LDL), creatinine (Cr), HBV DNA, CD3+ T cells count, CD4+ T cells count, CD8+ T cells count, CD4+ T cells/CD8+ T cells ratio, procalcitonin (PCT), serum amyloid A (SAA), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), alpha-fetoprotein (AFP), and IL-4 (P<0.05). LASSO regression analysis identified 5 variables: Child-Pugh grade, PVTT, WBC, CHE and hs-CRP. Binary logistic regression analysis indicated that Child-Pugh grade (Grade B: OR=5.780, 95%CI 3.271-10.213, P<0.001; Grade C:OR=14.818, 95%CI 7.697-28.526, P<0.001), PVTT (OR=2.893, 95%CI 2.037-4.108, P<0.001), WBC (OR=1.088, 95%CI 1.031-1.148, P=0.002), and hs-CRP (OR=1.005, 95%CI 1.001-1.010, P=0.026) were the independent risk factors of spontaneous peritonitis in HBV-related primary liver cancer patients. Using these 4 variables, a nomogram prediction model was constructed and evaluated. The P-value of the H-L goodness of fit test was 0.760. Moreover, the area under ROC curve (AUC) was 0.866, with a sensitivity of 0.870 and a specificity of 0.716. The average absolute error of the calibration curve is 0.022. DCA and CIC analyses demonstrated that the nomogram prediction model possessed some clinical utility.ConclusionThe nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer patients, constructed using Child-Pugh grade, PVTT, WBC and hs-CRP, exhibits a high fitting degree and accuracy, with the prediction probability highly consistent with the actual occurrence probability, and possesses certain clinical practicability.
摘要:ObjectiveTo compare the hemodynamic effects of anesthesia induction with remimazolam tosylate and etomidate in elderly frail patients.MethodsThis study was a single-center, prospective, randomized, single-blind trial. From January to April 2024, 96 elderly frail patients undergoing elective surgery in Fuyang People's Hospital were recruited. After excluding 6 cases (3 refused to participate, 1 had tracheal intubation time >30 s, and 2 had missing data), 90 patients were finally included. They were randomly divided into remimazolam tosylate group (intravenous injection of 0.2 mg/kg remimazolam tosylate for anesthesia induction, n=45) and etomidate group (intravenous injection of 0.3 mg/kg etomidate for anesthesia induction, n=45) by the random number table method. The area under the curve for mean arterial pressure (MAP) below or above baseline values (AUCMAP- and AUCMAP+), the heart rate (HR) below or above baseline values by 10% (AUCHR- and AUCHR+) within 10 minutes of anesthesia induction, the time to loss of consciousness, the time from the start of anesthesia induction to a bispectral index (BIS) <60, the incidence of drug-related adverse reactions, the incidence of cardiovascular adverse events, and the usage of vasoactive drug administrations were compared between the two groups.ResultsCompared with the etomidate group, the AUCMAP- (145.10±35.75 vs. 178.52±39.78) and AUCHR- [43.20(26.58, 56.35) vs. 54.99(43.01, 65.85)] in remimazolam tosylate group were significantly reduced (P<0.001, P=0.001). The time to loss of consciousness and the time from the start of anesthesia induction to BIS <60 were prolonged (P<0.001). The incidence of drug-related adverse reactions was significantly decreased (P<0.05), and the number of norepinephrine administrations was significantly reduced (P<0.05) in remimazolam tosylate group. However, there were no statistically significant differences in AUCMAP+, AUCHR+, the incidence of cardiovascular adverse events, and the usages of atropine, urapidil, and esmolol between the two groups (P>0.05).ConclusionThe use of remimazolam tosylate during anesthesia induction in elderly frail patients can provide more stable hemodynamic parameters and results in fewer adverse reactions than etomidate.
摘要:ObjectiveTo explore the application value of preoperative hemoglobin (Hb)/red cell distribution width (RDW) ratio (HRR), prognostic nutritional index (PNI) and carcinoembryonic antigen (CEA) in the diagnosis of colorectal cancer.MethodsData were retrospectively collected from 224 colorectal cancer patients admitted to Chaohu Hospital Affiliated to Anhui Medical University from September 2019 to December 2023, designated as colorectal cancer group, and 207 patients with benign colorectal diseases during the same period, designated as control group. General information, peripheral blood red cell, white cell, neutrophil, and lymphocyte counts, as well as CEA levels, were compared between the two groups. The HRR and PNI were calculated. Factors influencing the occurrence of colorectal cancer were analyzed. Multicollinearity analysis was performed on the selected variables, and variables with a variance inflation factor (VIF)<5 were included in the multivariate binary logistic regression analysis to identify independent influencing factors. A joint model was constructed using binary logistic regression analysis with HRR, PNI, and CEA. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic efficacy of HRR, PNI and CEA alone and in combination. Calibration curves and decision curve analysis (DCA) were used to evaluate the calibration and clinical utility of the joint model. Spearman rank correlation analysis was performed to assess the correlation between nutritional status of colorectal cancer patients (evaluated based on PNI values) and various nutritional indicators [body mass index (BMI), hemoglobin (Hb), albumin (ALB), red cell count and lymphocyte count].ResultsCompared with control group, patients in colorectal cancer group had lower level of red blood counts, HRR, and PNI, and higher levels of RDW and CEA, with statistically significant differences (P<0.001). Binary logistic regression analysis showed that ALB, CEA, HRR and PNI were independent risk factors for colorectal carcinogenesis(P<0.05 or P<0.01). ROC curve analysis revealed that HRR had the largest area under the curve (AUC) for diagnosing colorectal cancer (0.721), while PNI had the highest sensitivity (64.2%). The combined diagnosis of colorectal cancer using HRR, PNI and CEA had an AUC of 0.784, with the sensitivity and specificity of 67.0% and 84.1%, respectively. Internal validation, calibration curves, and DCA indicated that the joint model had good discrimination, consistency, and clinical performance. Spearman rank correlation analysis showed significant correlations between Hb, ALB levels, red cell and lymphocyte counts, and PNI (P<0.05). The worse the nutritional status of colorectal cancer patients (the lower PNI values), the lower the values of nutritional indicators.ConclusionsHRR and PNI have important diagnostic value for colorectal cancer and can improve diagnostic efficacy when combined with CEA. Moreover, PNI can effectively assess the nutritional status of colorectal cancer patients.
关键词:hemoglobin to erythrocyte distribution width ratio;prognostic nutritional index;colorectal cancer;diagnostic efficacy
摘要:ObjectiveTo explore the influencing factors on foot function recovery after distraction device-assisted repositioning of small incisions treatment for Sanders Ⅱ and Ⅲ calcaneal fractures, and to provide guidance for timely clinical interventions.MethodsA retrospective analysis was conducted on 80 patients with Sanders type Ⅱ and Ⅲ calcaneal fractures admitted to the People's Hospital of Bozhou from January 2021 to June 2023. Data were collected using a general information questionnaire, the hospital's electronic medical record system, the visual analog scale (VAS), the Marland foot function scale (MFS), the perceived social support scale (PSSS), and the perceived stress scale (PSS). The influencing factors of postoperative foot function recovery were analyzed using univariate factor analysis, multivariate linear regression, and structural equation modeling.ResultsThe MFS scores of 80 patients at 6 months post-operation were significantly higher than preoperative scores (P<0.001). The rates of excellent, good, fair, and poor foot function at 6 months post-operation were 56.3%, 31.3%, 10.0%, and 2.5%, respectively. Univariate analysis revealed significant differences in MFS scores based on different ages, time to start full weight-bearing exercise, bone mineral density, surgical timing, body mass index (BMI), postoperative VAS score, PSSS score, PSS score, and the presence of postoperative peroneal muscle spasm and peroneal muscle tendon adhesion (P<0.05). Multivariate linear regression identified age, time to start full weight-bearing exercise, surgical timing, BMI, postoperative fibular muscle spasm, postoperative fibular muscle tendon adhesion, postoperative VAS score, PSSS score, and PSS score as significant factors affecting foot function recovery (P<0.05). Structural equation modeling indicated that age, time to start full weight-bearing exercise, bone density, operative timing, BMI, postoperative peroneal muscle spasm, postoperative peroneal tendon adhesion, and pain severity directly influenced postoperative foot functional recovery. Additionally, psychological stress not only directly affected postoperative foot functional recovery but also indirectly influenced it through the mediating effect of social support.ConclusionsFoot function recovery after surgery for Sanders type Ⅱ and Ⅲ calcaneal fractures is influenced by multiple factors. Psychological stress not only directly affects the recovery of foot function after surgery, but also mitigates the harm to foot function through social support.
摘要:ObjectiveTo develop and evaluate a diagnostic model for autoimmune liver disease (AILD) using clinical indicators.MethodsA total of 181 AILD patients (AILD group) diagnosed in the Department of Gastroenterology or Rheumatology and Immunology, the First Medical Center of Chinese PLA General Hospital, from June 2019 to February 2024, 133 patients with hepatitis B virus cirrhosis (HBVC) (HBVC group), and 100 healthy individuals (HC group) were included in the study cohort for retrospective analysis. Clinical data, blood routine tests, and biochemical indicators were compared among the groups. Propensity score matching was used to balance the effects of factors such as gender and age. Multivariate logistic regression analysis was applied to identify characteristic indicators for AILD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of single and combined indicators, and the optimal diagnostic model for AILD was constructed. The Hosmer-Lemeshow test was performed to assess the model's goodness-of-fit, while ROC analysis was employed to evaluate the predictive validity. Additionally, an independent validation cohort, including 91 AILD patients (AILD validation group), 82 HBVC patients (HBVC validation group), and 40 healthy individuals (HC validation group) who visited during the same period, was used to validate the diagnostic model. False-positive and false-negative rates were calculated to assess the diagnostic efficacy and clinical utility of the model.ResultsThe age and the proportion of male patients in AILD and HBVC groups were higher than those in HC group, and the proportion of male patients in AILD group was higher than in HBVC group, the differences were statistically significant (P<0.05). Prior to matching, compared with HC group, HBVC group and AILD group had significantly lower levels of hemoglobin (HB), red blood cell count (RBC), white blood cell count (WBC), platelet count (PLT), and albumin (ALB) (P<0.05), but significantly higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), and direct bilirubin (DBIL) (P<0.05). Compared with HBVC group, AILD group had significantly higher levels of WBC, PLT, ALB, ALP, and GGT (P<0.05 or P<0.001) but significantly lower levels of TBIL and DBIL(P<0.001). After maching, compared with HC group, AILD group still had significantly lower levels of HB, RBC, WBC, PLT, and ALB, but significantly higher levels of ALT, AST, ALP, GGT, TBIL, and DBIL (P<0.05). Compared with HBVC group, AILD group had significantly higher levels of HB, RBC, WBC, PLT, ALB, ALT, ALP, and GGT, but significantly lower levels of DBIL (P<0.05). ROC analysis results showed that AST, GGT, ALP, and DBIL had high predictive values for differentiating AILD from HC (AUC=0.843, 0.804, 0.802, 0.773), while PLT, WBC, GGT, and ALP had high predictive values for differentiating AILD from HBVC (AUC=0.780, 0.739, 0.729, 0.702). For distinguishing AILD from HC, the combined model of AST, ALP, and DBIL (Model e) had an AUC of 0.887, with a sensitivity of 82.2%, and a specificity of 94.7%. For distinguishing AILD from HBVC, the combined model of ALP, GGT, and PLT (Model D) had an AUC of 0.829, with a sensitivity of 78.5% and a specificity of 80.6%. ConclusionsThe combined diagnostic model based on AST, ALP, and DBIL can effectively differentiate healthy individuals without liver diseases from AILD patients, while the combined diagnostic model based on PLT, ALP, and GGT can effectively distinguish HBVC from AILD patients.
摘要:ObjectiveTo explore the clinical and genetic characteristics of children with holocarboxylase synthetase (HLCS) deficiency.MethodsA retrospective analysis was conducted on the clinical data of 3 children with HLCS deficiency who were admitted to Children's Hospital Affiliated to Zhengzhou University from December 2014 to January 2024. Relevant literature indexed in CNKI, Wanfang Data, PubMed and other databases was reviewed to summarize the clinical characteristics and HLCS gene mutations of children with HLCS deficiency.ResultsAll 3 children were male, with onset age of 4-6 months. The main clinical manifestations included shortness of breath, vomiting, diarrhea, and poor mental state, and partial cases were complicated by growth retardation and neurological symptoms. Laboratory tests showed metabolic acidosis in all cases, blood amino acid and acylcarnitine profiles as well as urinary organic acid analysis suggested multiple carboxylase deficiency. Genetic testing revealed compound heterozygous mutation in the HLCS gene of all 3 children, among which the c.1892delT(p.L631X) mutation was previously unreported. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.1892delT(p.L631X) mutation was rated as pathogenic mutation (PVS1+PM2_supporting+PM3). Biotin supplementation was effective in all cases. Literature review included 27 English literatures and 29 Chinese literatures, reporting a total of 133 children with HLCS deficiency caused by HLCS gene mutation. Common clinical manifestations included metabolic acidosis, skin lesions, vomiting, feeding difficulties, dyspnea, diarrhea, and neurological symptoms, etc. ConclusionsBlood amino acid and acylcarnitine profiles, urine organic acid analysis, and gene testing are helpful for the diagnosis of HLCS deficiency. Timely biotin supplementation leads to a good prognosis. The mutation of HLCS gene is considered as the genetic etiology of HLCS deficiency in 3 children, among which the c.1892delT(p.L631X) mutation is a newly discovered mutation.
摘要:ObjectiveTo specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells (BMSCs) after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase (MetRSL247G) for nascent protein labeling, in order to explore the potential mechanisms of action in BMSCs post-transplantation.MethodsPoint mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine (ANL)-mediated labeling of nascent proteins in BMSCs. The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging (FUNCAT). Thirty healthy female C57BL/6J mice (8-10 weeks old) were divided into control and experimental groups, with 15 mice in each group. The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group, while control mice underwent only thoracotomy without coronary ligation. After modeling, both groups received intramyocardial injections of MetRSL247G-modified BMSCs (MetRSL247G-BMSCs) at 3 different sites in the peri-infarct ischemic region. Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0, 2, and 6 (n=5 for each time point) respectively, euthanized 24 h after the last injection, and cardiac tissues were isolated. The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected, using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry (LC-MS) analysis. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) analysis, and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.ResultsUnder fluorescence microscopy, the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals, confirming the successful construction of the MetRSL247G-BMSCs cell line. Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL, validating the sensitivity and specificity of the labeling method. GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation, extracellular matrix organization, and focal adhesion. KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway, actin cytoskeleton regulation pathway, and apoptosis pathway. Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1 (P<0.05), upregulated anti-apoptotic factors, pro-apoptotic factors, and cell adhesion-related factors on day 3 (P<0.05), and upregulated anti-apoptotic factors, cell differentiation-related factors, and cell adhesion-related factors on day 7 (P<0.05) compared with control group. Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7 (P<0.05). On day 3, most differentially expressed proteins, including anti-apoptosis factors (Protein S100-A11, Clusterin, Gelsolin), pro-apoptosis factor (Cathepsin B), cell differentiation-related factor (Transgelin-2), and cell adhesion-related factors (Cofilin-1, Periostin, Fibronectin) were significantly upregulated (P<0.05).ConclusionsThe MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins, confirming the feasibility of this nascent protein labeling technique. Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization. BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades, activating inflammatory factors, regulating actin cytoskeleton structure, and modulating apoptosis, thereby maintaining the survival of BMSCs.
摘要:ObjectiveTo investigate the mechanism by which long non-coding RNA (lncRNA) AI662270 regulates insulin resistance in adipocytes in aging mice.Methods(1) Twenty male C57BL/6 mice were randomly divided into youth (4-month-old) group and aged (18-month-old) group (n=10). Mice in youth group were raised to 4 months of age and euthanized by orbital exsanguination under urethane anesthesia, while aged mice were euthanized at 18 months using the same sacrifice method. Epididymal white adipose tissue (eWAT) and liver tissue were rapidly dissected. Western blotting was employed to detect the protein expression levels of tumor suppressor gene 1 (p16ink4a) and cyclin-dependent kinase inhibitor p21 (p21kip1), RT-qPCR was used to measure the expression of 4 differentially expressed lncRNAs (C4a, AI662270, BATE1 and Gm29719). Mouse embryonic fibroblasts (3T3-L1) were cultured and divided into a normal control group (no treatment after induced differentiation into mature adipocytes) and a senescence model group [doxorubicin (ADR)-treated group; 0.2 μmol/L ADR was used to induce senescent adipocytes]. β-galactosidase staining was performed to assess adipocyte senescence. RT-qPCR was applied to evaluate the expression of AI662270 and senescence markers (p16ink4a, p21kip1, p53), while Western blotting was utilized to detect the expression levels of phosphorylated H2A histone family member X (γ-H2AX), p16ink4a, and p21kip1 proteins. (2) Hexokinase method was adopted to measure glucose content in mouse serum and 3T3-L1 adipocyte culture medium. RT-qPCR was performed to analyze mRNA expression levels of insulin sensitivity-related gene protein kinase B (Akt), insulin receptor substrate 1 (IRS1), phosphatidylinositol 3 kinase (PI3K) and glucose transporter 4 (GLUT4) in mouse eWAT and adipocytes. Western blotting was conducted to determine the protein expression levels of IRS1, PI3K, Akt, and p-Akt. (3) Spearman correlation analysis was applied to examine the correlation between AI662270 expression levels and IRS1/PI3K mRNA expression levels. A low-expression model of AI662270 in senescent adipocytes was constructed, and RT-qPCR was used to verify the knockdown efficiency. Hexokinase method was employed to assess glucose content in the cell culture medium of senescent adipocytes after AI662270 knockdown. RT-qPCR was performed to measure the mRNA expressions of Akt, IRS1, IRS2, and PI3K, while Western blotting was utilized to detect the expressions levels of Akt and p-Akt proteins. (4) Bioinformatics analysis was performed to predict downstream target genes of AI662270 and their binding sites. RT-qPCR and Western blotting were subsequently applied to validate the expression of these downstream target genes following AI662270 knockdown.Results(1) Compared with youth group, the protein expression levels of p16ink4a and p21kip1 in eWAT of aged mice were significantly increased (P<0.05). Additionally, the expression levels of C4a, AI662270, BATE1, and Gm29719 in both eWAT and liver tissues were significantly increased in aged group (P<0.05). β-galactosidase staining revealed enhanced blue-green coloration and enlarged, flattened cellular morphology in ADR-treated senescent adipocytes compared with normal control group. Compared with normal control group, ADR-treated senescent adipocytes significantly increased the mRNA expression levels of AI662270, p16ink4a, and p21kip1, and significantly elevated protein expression levels of γ-H2AX, p16ink4a, and p21kip1 (P<0.05). (2) Serum glucose content was significantly higher in aged group mice compared with youth group (P<0.01), and glucose content in the adipocyte culture medium in ADR group was significantly increased (P<0.05). The expression levels of IRS1 and PI3K in eWAT in aged group were significantly reduced compared with youth group (P<0.01). Compared with normal control group, the expression levels of IRS1 and PI3K in adipocytes in ADR-treated group were also significantly reduced (P<0.05). (3) Spearman correlation analysis demonstrated that the expression level of AI662270 was negatively correlated with the mRNA expression levels of IRS1 and PI3K (P<0.05). RT-qPCR showed that AI662270 expression level was significantly reduced in the siAI662270-transfected senescent adipocytes compared with siNC group (P<0.05), indicating the low expression model of aged adipocytes AI662270 was successfully constructed. Hexokinase assay results showed that glucose content in the cell culture medium was significantly reduced after the AI662270 was knocked down by senescent adipocytes(P<0.05). Furthermore, the mRNA expression levels of IRS1, IRS2 and PI3K (P<0.05) and the p-Akt/Akt ratio in senescent adipocytes was significantly increased after knockdown of AI662270 (P<0.01). (4) Bioinformatics analysis predicted miR-3073b-3p as a downstream target gene of AI662270, and heme oxygenase 1 (Hmox1) was identified as a target molecule of miR-3073b-3p. The expression level of miR-3073b-3p in senescent adipocytes in siAI662270 group was significantly increased, while the mRNA and protein expression level of Hmox1 were significantly decreased compared with siNC group (P<0.01).ConclusionsAging significantly increases the expression of AI662270 in eWAT of mice, and the expression of AI662270 was negatively correlated with insulin sensitivity. AI662270 knockdown can reduce glucose content in senescent adipocyte culture medium, upregulate the expression of IRS1 and PI3K, and increase insulin sensitivity in senescent adipocytes, which may be mediated through the AI662270/miR-3073b-3p/Hmox1 pathway.
关键词:aging;epididymal white adipose tissue;insulin resistance;long non-coding RNA AI662270
摘要:ObjectiveTo explore the effects of Rhodiola salidroside on regulating the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) signaling pathway and explore its impact on hippocampal neuron autophagy and apoptosis induced by oxygen-glucose deprivation/reperfusion (OGD/R).MethodsThe mouse hippocampal neuronal cell line HT22 was cultured in vitro and randomly divided into control group, OGD/R group, salidroside group, tert-butylhydroquinone (TBHQ) group, and salidroside+TBHQ group. Except for control group, cell models were established by OGD/R induction in other groups. Cells in corresponding groups were treated with Rhodiola salidroside (500 μmol/L) and/or MAPK activator TBHQ (50 μmol/L) for 24 h. The lactate dehydrogenase (LDH) release rates were measured, cell apoptosis was detected by flow cytometry, and cell viability was assessed by MTT assay. Acridine orange (AO) staining was used to detect autophagy. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of inflammatory cytokines including interleukins (IL)-6, IL-8, and IL-17, and tumor necrosis factor-α (TNF-α). Western blotting was performed to detect the expression levels of proteins related to apoptosis, autophagy, and the MAPK/ERK/mTOR signaling pathway.ResultsSalidroside (500 μmol/L) significantly enhanced the viability of OGD/R-induced HT22 cells (P<0.05), without obvious effect on the viability of normally cultured HT22 cells (P>0.05). Compared with control group, OGD/R group showed significantly increased LDH release rates, apoptosis rates, autophagosome formation rates, levels of IL-6, IL-8, IL-17 and TNF-α, expressions of Bcl-2-associated X protein (Bax), Cleaved Caspase-3, Caspase-3 and Beclin-1 protein, ratios of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ, phosphorylation (p)-p38 MAPK/p38 MAPK, and p-ERK1/2/ERK1/2 (P<0.05), while cell viability and p-mTOR/mTOR ratio were significantly decreased (P<0.05). Compared with OGD/R group, salidroside group had significantly reduced LDH release rates, apoptosis rates, autophagosome formation rates, levels of IL-6, IL-8, IL-17, and TNF-α, expressions of Bax, Cleaved Caspase-3, Caspase-3, Beclin-1 protein, and ratios of LC3-Ⅱ/LC3-Ⅰ ratio, p-p38 MAPK/p38 MAPK, and p-ERK1/2/ERK1/2 (P<0.05), while cell viability and p-mTOR/mTOR ratio were significantly increased (P<0.05). The change of indicators in TBHQ group showed an opposite trend to those in salidroside (P<0.05). Compared with salidroside group, salidroside+TBHQ group had significantly increased LDH release rates, apoptosis rates, autophagosome formation rates, levels of IL-6, IL-8, IL-17 and TNF-α, expressions of Bax, Cleaved Caspase-3, Caspase-3, Beclin-1 protein, and ratios of LC3-II/LC3-I, p-p38 MAPK/p38 MAPK, and p-ERK1/2/ERK1/2 (P<0.05), while cell viability and p-mTOR/mTOR ratio were significantly decreased (P<0.05).ConclusionSalidroside may inhibit OGD/R-induced hippocampal neuron autophagy and apoptosis by blocking the activation and transmission of MAPK/ERK/mTOR signaling pathway.
关键词:salidroside;oxygen-glucose deprivation/reperfusion;mitogen-activated protein kinase;hippocampal neurons;autophagy;apoptosis
摘要:Spinal cord injury (SCI) is a serious central nervous system traumatic disease that usually leads to severe neurological dysfunction below the site of injury. Studies have shown that SCI is closely related to oxidative stress, inflammatory responses, and mitochondrial dynamic imbalance. Mitochondrial dysfunction, such as accumulation of mitochondrial DNA damage, depletion of ATP, and impairment of oxidative stress regulation, can lead to dysfunction or death of neurons. Mitochondrial fusion plays a key role in maintaining energy balance and promoting neurological recovery after SCI. This review summarizes the changes in mitochondrial dynamics after SCI and the neuroprotective mechanisms mediated by mitochondrial fusion, with aim to provide new ideas on the treatment of SCI.
摘要:Non-cystic fibrosis bronchiectasis (referred to as bronchiectasis) is a common chronic airway disease. Neutrophils have traditionally been considered to play a dominant role in the airway inflammation of bronchiectasis. However, it has been discovered that approximately 20% to 30% of bronchiectasis patients exhibited elevated eosinophil counts (Sputum eosinophil ratio>3% or blood eosinophil count >300/μl) in their sputum and blood samples, referred to as eosinophilic bronchiectasis (EB). Based on this novel discovery of the inflammatory phenotype, some scholars have advocated treating bronchiectasis as an "inflammatory disease" rather than an "infectious disease" in a novel therapeutic approach. This article reviews the discovery and the latest research advancements of EB, exploring its pathophysiological basis, clinical characteristics, and treatment, with the aim to facilitate the understanding and management of EB.
关键词:bronchiectasis;eosinophilic bronchiectasis;blood eosinophil count;inflammatory type
摘要:The cell membrane biomimetic nanodrug delivery platform consists of nanoparticles coated with drug-loaded cell membranes, demonstrating a significant anti-atherosclerosis effect. This platform can identify and bind to atherosclerotic plaques through the homing capabilities of cell membranes. It releases drugs in response to specific environmental triggers, such as reactive oxygen species and shear stress from blood flow in areas affected by atherosclerosis. Furthermore, it inhibits macrophage lipid phagocytosis, thereby reducing foam cell formation, regulating macrophage phenotypes, and decreasing the production of inflammatory factors. Additionally, it accelerates cholesterol dissolution and efflux in atherosclerotic regions, effectively removes high concentrations of reactive oxygen species, and mitigates oxidative stress damage as well as the deposition of oxidized low-density lipoprotein. This review article delves into the functions and mechanisms of cell membrane biomimetic nanodrug delivery platform in combating atherosclerosis, offering fresh insights for targeted atherosclerosis treatment through the lens of nanomedicine.
摘要:Mesenchymal stem cells (MSCs) are multifunctional progenitor cells with self-renewal capabilities and have emerged as promising therapeutic cells in the field of regenerative medicine. Exosomes (EXOs), nanoscale vesicles secreted by cells, carry a variety of bioactive molecules and play a crucial role in intercellular communication.Recent studies suggest that the therapeutic effects of MSCs are largely mediated through paracrine mechanisms, with EXOs considered as key effectors in this process. Mesenchymal stem cell-derived exosomes (MSC-EXOs) exhibit biological activities similar to those of MSC, including anti-inflammatory, anti-apoptotic, and tissue repair-promoting properties. In addition, MSC-EXOs possess unique advantages such as structural stability, targeting capability, and nanoscale dimensions, which endow them with significant potential for the treatment of central nervous system (CNS) disorders, particularly neonatal brain injuries. This review summarizes the biological characteristics of EXO and highlights the therapeutic applications and underlying mechanisms of MSC-EXOs in neonatal hypoxic-ischemic encephalopathy and brain injuries associated with preterm birth.
摘要:Early postoperative hypoxemia, a common adverse event following general anesthesia, is closely associated with pathophysiological changes in patients, prolonging stays in the post-anesthesia care unit (PACU) and intensive care unit (ICU), and correlating with increased one-year postoperative mortality rate. Nevertheless, due to differences in definitions of hypoxemia, heterogeneity of study populations, and variations in postoperative monitoring methods, the reported incidence and duration of early postoperative hypoxemia in the literature vary significantly. This review systematically summarizes relevant literature to elucidate the definition and characteristic indicators of early postoperative hypoxemia, and explores its correlations with postoperative respiratory complications, cardiovascular complications, and surgical site infections. By analyzing existing research evidence, this review aims to identify early-warning indicators of postoperative hypoxemia with predictive value, thereby providing a reference for future research in this field.
关键词:postoperative hypoxemia;complications;respiratory system;cardiovascular system;surgical site infection