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JMIR Bioinformatics and Biotechnology May 2024The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with...
BACKGROUND
The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms.
OBJECTIVE
We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors.
METHODS
We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models.
RESULTS
We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively.
CONCLUSIONS
The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (P<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.
PubMed: 38935968
DOI: 10.2196/56884 -
Combinatorial Chemistry & High... Jun 2024The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy...
AIM
The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC).
METHODS
This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50.
RESULTS
In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators.
CONCLUSIONS
NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.
PubMed: 38934277
DOI: 10.2174/0113862073305230240611091708 -
Pharmaceuticals (Basel, Switzerland) May 2024The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population...
AIMS
The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile.
METHODS
Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges.
RESULTS
A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CL), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM.
CONCLUSIONS
We found that qCRP, CRRT, CL, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.
PubMed: 38931333
DOI: 10.3390/ph17060665 -
Materials (Basel, Switzerland) Jun 2024The paper presents the study concerning the preparation and physio-chemical and biological properties of wool-copper (WO-Cu) materials obtained by the sputter deposition...
The paper presents the study concerning the preparation and physio-chemical and biological properties of wool-copper (WO-Cu) materials obtained by the sputter deposition of copper onto the wool fibers. The WO-Cu material was subjected to physio-chemical and biological investigations. The physio-chemical investigations included the elemental analysis of materials (C, N, O, S, and Cu), their microscopic analysis, and surface properties analysis (specific surface area and total pore volume). The biological investigations consisted of the antimicrobial activity tests of the WO-Cu materials against colonies of Gram-positive () bacteria, Gram-negative () bacteria, and fungal mold species (). Biochemical-hematological tests included the evaluation of the activated partial thromboplastin time and pro-thrombin time. The tested wool-copper demonstrated the ability to interact with the DNA in a time-dependent manner. These interactions led to the DNA's breaking and degradation. The antimicrobial and antifungal activities of the WO-Cu materials suggest a potential application as an antibacterial/antifungal material. Wool-copper materials may be also used as customized materials where the blood coagulation process could be well controlled through the appropriate copper content.
PubMed: 38930247
DOI: 10.3390/ma17122878 -
Animals : An Open Access Journal From... Jun 2024This study explored the effects of hyperbaric oxygen therapy (HBOT) on hemogram, serum biochemistry and hemostatic variables in female dogs undergoing...
BACKGROUND
This study explored the effects of hyperbaric oxygen therapy (HBOT) on hemogram, serum biochemistry and hemostatic variables in female dogs undergoing laparoscopic-assisted ovariohysterectomy (OVH).
MATERIALS
Thirty adult, mixed-breed, healthy female dogs were randomly divided into the following three groups: HBOT + SURG (exposed to two absolute atmospheres (ATAs) for 45 min followed by laparoscopic-assisted OVH), HBOT (exposed to two ATAs for 45 min) and SURG (laparoscopic-assisted OVH). Blood samples were collected at T0 (at the admission), at T1, 24 h after T0 (immediately after HBOT in the HBOT + SURG and HBOT groups, and immediately before anesthetic premedication in the SURG group), and at T2, 48 h after T0 (24 h after HBOT and anesthetic premedication).
METHODS
Assessments included erythrogram, leukogram, thrombogram, renal and hepatic serum biochemistry, prothrombin time (PT), activated partial thromboplastin time (APTT), buccal mucosal bleeding time (BMBT) and bloodstain area (BA) on hygroscopic paper collected at the BMBT.
RESULTS
Both the HBOT + SURG and SURG groups presented neutrophilia ( ≤ 0.0039) at T2 and an increase of ALP at T2 ( ≤ 0.0493), the SURG group presented an increase in leukocyte count at T2 ( = 0.0238) and the HBOT + SURG group presented a reduction in lymphocyte count at T2 ( = 0.0115). In the HBOT + SURG group, there was a reduction in PT and APTT in relation to the baseline value ( ≤ 0.0412).
CONCLUSIONS
A session of HBOT at two ATAs for 45 min did not cause changes in the BMBT or BA in healthy female dogs. Some blood parameters investigated (neutrophil and lymphocyte count, ALP, PT and APTT) were affected by the use of HBOT.
PubMed: 38929404
DOI: 10.3390/ani14121785 -
Children (Basel, Switzerland) Jun 2024Prior guidelines recommended maintaining normothermia following traumatic brain injury (TBI), but recent studies suggest therapeutic hypothermia as a viable option in... (Review)
Review
BACKGROUND
Prior guidelines recommended maintaining normothermia following traumatic brain injury (TBI), but recent studies suggest therapeutic hypothermia as a viable option in pediatric cases. However, some others demonstrated a higher mortality rate. Hence, the impact of hypothermia on neurological symptoms and overall survival remains contentious.
METHODS
We conducted a systematic review and meta-analysis to evaluate the effects of hypothermia on neurological outcomes in pediatric TBI patients. The PubMed/Medline, Scopus, and Web of Science databases were searched until 1 January 2024 and data were analyzed using appropriate statistical methods.
RESULTS
A total of eight studies, comprising nine reports, were included in this analysis. Our meta-analysis did not reveal significant differences in mortality (RR = 1.58; 95% CI = 0.89-2.82, = 0.055), infection (RR = 0.95: 95% CI = 0.79-1.1, = 0.6), arrhythmia (RR = 2.85: 95% CI = 0.88-9.2, = 0.08), hypotension (RR = 1.54: 95% CI = 0.91-2.6, = 0.10), intracranial pressure (SMD = 5.07: 95% CI = -4.6-14.8, = 0.30), hospital length of stay (SMD = 0.10; 95% CI = -0.13-0.3, = 0.39), pediatric intensive care unit length of stay (SMD = 0.04; 95% CI = -0.19-0.28, = 0.71), hemorrhage (RR = 0.86; 95% CI = 0.34-2.13, = 0.75), cerebral perfusion pressure (SMD = 0.158: 95% CI = 0.11-0.13, = 0.172), prothrombin time (SMD = 0.425; 95% CI = -0.037-0.886, = 0.07), and partial thromboplastin time (SMD = 0.386; 95% CI = -0.074-0.847, = 0.10) between the hypothermic and non-hypothermic groups. However, the heart rate was significantly lower in the hypothermic group (-1.523 SMD = -1.523: 95% CI = -1.81--1.22 < 0.001).
CONCLUSIONS
Our findings challenge the effectiveness of therapeutic hypothermia in pediatric TBI cases. Despite expectations, it did not significantly improve key clinical outcomes. This prompts a critical re-evaluation of hypothermia's role as a standard intervention in pediatric TBI treatment.
PubMed: 38929280
DOI: 10.3390/children11060701 -
International Journal of Molecular... Jun 2024Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients...
Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients by analyzing creatinine time-series data to identify distinct AKI clusters and evaluating routine biomarkers' predictive values. A retrospective cohort analysis was performed on 2608 adult burn patients admitted to Hangang Sacred Heart Hospital's Burn Intensive Care Unit (BICU) from July 2010 to December 2022. Patients were divided into four clusters based on creatinine trajectories, ranging from high-risk, severe cases to lower-risk, short-term care cases. Cluster A, characterized by high-risk, severe cases, showed the highest mortality and severity, with significant predictors being PT and TB. Cluster B, representing intermediate recovery cases, highlighted PT and albumin as useful predictors. Cluster C, a low-risk, high-resilience group, demonstrated predictive values for cystatin C and eGFR cys. Cluster D, comprising lower-risk, short-term care patients, indicated the importance of PT and lactate. Key biomarkers, including albumin, prothrombin time (PT), cystatin C, eGFR cys, and total bilirubin (TB), were identified as significant predictors of AKI development, varying across clusters. Diagnostic accuracy was assessed using area under the curve (AUC) metrics, reclassification metrics (NRI and IDI), and decision curve analysis. Cystatin C and eGFR cys consistently provided significant predictive value over creatinine, with AUC values significantly higher ( < 0.05) in each cluster. This study highlights the need for a tailored, biomarker-driven approach to AKI management in burn patients, advocating for the integration of diverse biomarkers in clinical practice to facilitate personalized treatment strategies. Future research should validate these biomarkers prospectively to confirm their clinical utility.
Topics: Humans; Biomarkers; Burns; Acute Kidney Injury; Male; Female; Middle Aged; Adult; Retrospective Studies; Creatinine; Cystatin C; Aged; Glomerular Filtration Rate
PubMed: 38928473
DOI: 10.3390/ijms25126769 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To identify the genetic mutation of coagulation factor Ⅶ ( ) gene in a pedigree with coagulation factor Ⅶ (FⅦ) deficiency and explore the molecular pathogenesis.
OBJECTIVE
To identify the genetic mutation of coagulation factor Ⅶ ( ) gene in a pedigree with coagulation factor Ⅶ (FⅦ) deficiency and explore the molecular pathogenesis.
METHODS
The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (DD), fibrin degradation products (FDP) and coagulation factor Ⅶ activity (FⅦ:C) of the proband and her family members were detected by Sysmex-CS5100 analyzer. All exons and exon-intron boundaries of the gene were amplified by PCR followed by direct sequencing. The detected mutation was confirmed by reverse sequencing. The ClustalW software was used to analyze the conservatism of the mutant site. Pathogenicity of the mutation was assessed with Mutation Taster and PolyPhen-2 online bioinformatics software. Structure of the mutant protein was analyzed using Swiss-PdbViewer software.
RESULTS
The results of routine coagulation tests showed that PT of the proband was markedly extended to 42.5 s, and her FⅦ:C significantly reduced to 2%. The FⅦ:C of her grandmother, mother and sister had slightly reduced to 49%, 51%, and 42%, respectively. These coagulant parameters of her father were within the normal range. Genetic analysis reveled a heterozygous G>A change at cDNA 646 in exon 6 of gene in the proband, resulting in a replacement of glycine at 156 of FⅦ catalytic region with serine (p.Gly156Ser). The sequencing results of other exons and exon-intron boundaries of her gene were normal. The proband's grandmother, mother and sister were all the carriers of this missense mutation except her father. Bioinformatics analysis showed that the p.Gly156Ser mutation caused polarity change of the amino acid at this site and formation of side chains, leading to increase of protein instability, which may affect catalytic activity of structural domain. Meanwhile, both Mutation Taster and PolyPhen-2 online bioinformatics software also predicted the pathogenicity of this missense mutation with high scores.
CONCLUSION
The heterozygous p.Gly156Ser mutation is the direct cause of the reduced FⅦ in this proband.
Topics: Humans; Female; Factor VII; Pedigree; Factor VII Deficiency; Mutation; Exons; Heterozygote; Male
PubMed: 38926980
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.032 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the intervention effect and mechanism of regulating miR-155 on young rats with dysfunction of blood coagulation.
OBJECTIVE
To investigate the intervention effect and mechanism of regulating miR-155 on young rats with dysfunction of blood coagulation.
METHODS
Twenty-six healthy and clean SD male rats were selected to establish the coagulopathy models. Twenty-four rats successfully established models and were randomly divided into three groups: model group, up-regulated miR-155 group and down-regulated miR-155 group, with 8 rats in each group. The expression of miR-155 was detected by real-time fluorescence quantitative polymerase chain reaction. The changes of coagulation factors and coagulation indicators were observed. Liver pathological tissues were observed by HE staining. The expressions of HMGB1-RAGE/TLRs-NF-κB signaling pathway related proteins were detected by Western blot.
RESULTS
Compared with model group, the expressions of HMGB1, RAGE, TLR2, TLR4 and NF-κB were significantly increased in up-regulated miR-155 group (all < 0.05), while decreased in down-regulated miR-155 group (all < 0.05). Compared with model group, the expressions of coagulation factor Ⅱ, Ⅶ, Ⅸ, and Ⅹ were significantly decreased in up-regulated miR-155 group (all < 0.05), while increased in down-regulated miR-155 group ( < 0.05). There was no significant difference in the expression of coagulation factor Ⅺ among the three groups ( >0.05). Compared with model group, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower and fibrinogen (FIB) was higher in up-regulated miR-155 group (all < 0.05), while in the down-regulated miR-155 group they were opposite.
CONCLUSION
Down-regulation of miR-155 can effectively improve coagulation factors and coagulation indexes and inhibit inflammation in young rats with dysfunction of blood coagulopathy, and the mechanism may be related to HMGB1-RAGE/TLRs-NF-κB signaling pathway.
Topics: Animals; MicroRNAs; Rats; Male; Rats, Sprague-Dawley; NF-kappa B; Blood Coagulation; HMGB1 Protein; Signal Transduction; Blood Coagulation Disorders; Down-Regulation; Toll-Like Receptor 4; Blood Coagulation Factors; Toll-Like Receptor 2
PubMed: 38926979
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.031 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To evaluate the clinical and prognostic value of prothrombin time (PT) and activated partial thromboplastin time (APTT) in newly diagnosed patients with multiple myeloma...
OBJECTIVE
To evaluate the clinical and prognostic value of prothrombin time (PT) and activated partial thromboplastin time (APTT) in newly diagnosed patients with multiple myeloma (MM).
METHODS
The clinical data of 116 newly diagnosed MM patients in the Second Hospital and Third Hospital of Shanxi Medical University from October 2014 to March 2022 were analyzed retrospectively, and the patients were divided into two groups: normal PT and APTT group and prolonged PT or APTT group. The differences in sex, age, classification, staging, bleeding events, laboratory indicators [including hemoglobin (Hb), platelet count (PLT), serum calcium, serum albumin (ALB), lactate dehydrogenase (LDH), serum creatinine and β-microglobulin], and cytogenetic characteristics between the two groups of patients were compared. The effect of prolonged PT or APTT on survival of patients with MM was analyzed.
RESULTS
Compared with patients in normal PT and APTT group, patients in prolonged PT or APTT group were more likely to experience bleeding events (=5.087, =0.024), with lower ALB levels (=4.962, =0.026) and PLT levels (=4.309, =0.038), and higher serum calcium levels (=5.056, =0.025). The positive rates of del17p, del13q and 1q21+ in prolonged PT or APTT group were higher than those in normal PT and APTT group, but the difference was not statistically significant ( >0.05). K-M survival analysis showed that the prolonged PT or APTT group had a shorter median progression-free survival (PFS) ( =0.032) and overall survival (OS) ( =0.032). Multivariate Cox analysis showed that prolonged PT or APTT (=2.116, 95% :1.025-4.372, =0.043) and age ≥65 years (=2.403, 95% : 1.195-4.836, =0.014) were independent risk factor for OS in newly diagnosed MM patients. However, prolonged PT or APTT had no significant effect on PFS of newly diagnosed MM patients (=1.162, 95% : 0.666-2.026, =0.597).
CONCLUSION
Newly diagnosed MM patients with prolonged PT or APTT have worse clinical indicators, shorter PFS and OS. Prolonged PT or APTT is an independent risk factor for OS in MM patients.
Topics: Humans; Multiple Myeloma; Partial Thromboplastin Time; Prognosis; Retrospective Studies; Prothrombin Time; Male; Female; Middle Aged
PubMed: 38926971
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.023