UNASSIGNED: Recent research indicates that the monocyte lymphocyte ratio (MLR), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), C-reactive protein (CRP), and systemic immune-inflammation index (SII) may serve as valuable predictors of early postoperative mortality in elderly individuals with hip fractures. The primary objective of the study was to examine the association between preoperative MLR, NLR, PLR, CRP, and SII levels and 3-year mortality risk in geriatric patients after hip fracture surgery.
UNASSIGNED: The study included patients aged 65 years or older who underwent hip fracture surgery between November 2018 and November 2019. Admission levels of MLR, NLR, PLR, CRP, and SII were measured. The median follow-up period was 3.1 years. Cox proportional hazards models were used to calculate the hazard ratio (HR) for mortality with adjusting for potential covariates. Time-dependent receiver operating characteristic (ROC) curves were employed to assess the predictive capability of inflammatory indicators for mortality.
UNASSIGNED: A total of 760 patients completed the follow-up (79.4 ± 7.8 years, 71.1% female). A higher preoperative MLR was found to be significantly associated with an increased 3-year postoperative mortality risk (HR 1.811, 95% CI 1.047-3.132, P = 0.034). However, no significant correlations were observed between preoperative NLR, PLR, CRP, SII and 3-year mortality. The areas under the ROC curve (AUCs) of MLR for predicting 30-day, 120-day, 1-year, and 3-year mortality were 0.74 (95% CI 0.53-0.95), 0.70 (95% CI 0.57-0.83), 0.67 (95% CI 0.60-0.74), and 0.61 (95% CI 0.56-0.66), respectively.
UNASSIGNED: Preoperative MLR is a useful inflammatory marker for predicting 3-year mortality in elderly hip fracture patients, but its predictive ability diminishes over time.

Acetylcholinesterase (AChE) is one of the main drug targets for treating Alzheimer\'s disease. This current study relies on multiple molecular modeling approaches to develop new potent inhibitors of AChE. We explored a 2D QSAR study using the statistical method of multiple linear regression based on a set of substituted 5-phenyl-1,3,4-oxadiazole and N-benzylpiperidine analogs, which were recently synthesized and proved their inhibitory activities against acetylcholinesterase (AChE). The molecular descriptors, polar surface area, dipole moment, and molecular weight are the key structural properties governing AChE inhibition activity. The MLR model was selected based on its statistical parameters: R2 = 0.701, R2test = 0.76, Q2CV = 0.638, and RMSE = 0.336, demonstrating its predictive reliability. Randomization tests, VIF tests, and applicability domain tests were adopted to verify the model\'s robustness. As a result, 11 new molecules were designed with higher anti-Alzheimer\'s activities than the model molecule. We demonstrated their improved pharmacokinetic properties through an in silico ADMET study. A molecular docking study was conducted to explore their AChE inhibition mechanisms and binding affinities in the active site. The binding scores of compounds M1, M2, and M6 were (-12.6 kcal/mol), (-13 kcal/mol), and (-12.4 kcal/mol), respectively, which are higher than the standard inhibitor Donepezil with a binding score of (-10.8 kcal/mol). Molecular dynamics simulations over 100 ns were used to validate the molecular docking results, indicating that compounds M1 and M2 remain stable in the active site, confirming their potential as promising anti-AChE inhibitors.

UNASSIGNED: Hierarchical management is advocated in China to effectively manage chronic obstructive pulmonary disease (COPD) patients and reduce the incidence and mortality of acute exacerbation of COPD (AE-COPD). However, primary and community hospitals often have limited access to advanced equipment and technology. Complete blood count (CBC), which is commonly used in these hospitals, offers the advantages of being cost-effective and easily accessible. This study aims to evaluate the significance of routine blood indicators in aiding of diagnosing AE-COPD.
UNASSIGNED: In this research, we enrolled a total of 112 patients diagnosed with AE-COPD, 92 patients with stable COPD, and a control group comprising 60 healthy individuals. Clinical characteristics, CBC parameters, and serum CRP levels were collected within two hours. To assess the associations between NLR/PLR/MLR and CRP by Spearman correlation test. The diagnostic accuracy of NLR, PLR and MLR in AE-COPD was assessed using Receiver Operating Characteristic Curve (ROC) and the area under the curve (AUC). Binary Logistic Regression analysis was conducted for the indicators of NLR, PLR and MLR.
UNASSIGNED: We found that patients with AE-COPD had significantly higher levels of NLR, PLR and MLR in contrast to patients with stable COPD. Additionally, the study revealed a noteworthy correlation between CRP and NLR (rs=0.5319, P<0.001), PLR (rs=0.4424, P<0.001), and MLR (rs=0.4628, P<0.001). By utilizing specific cut-off values, the amalgamation of NLR, PLR and MLR augmented diagnostic sensitivity. Binary logistic regression analysis demonstrated that heightened NLR and MLR act as risk factors for the progression of AE-COPD.
UNASSIGNED: The increasing levels of NLR, PLR and MLR could function as biomarkers, akin to CRP, for diagnosis and assessment of acute exacerbations among COPD patients. Further research is required to validate this concept.

Background: Subarachnoid hemorrhage is a devastating disease. Even after state-of-the-art treatment patients suffer from complications, including cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and chronic hydrocephalus (CH) following aneurysmal subarachnoid hemorrhage (aSAH). The aim of our study is to identify the predictive value of the C-reactive protein to lymphocyte ratio (CLR) for neurological functional outcome and complications after aSAH. Methods: We retrospectively analyzed a total of 166 aSAH patients who met the inclusion criteria enrolled in our study. Multivariate logistic regression analyses were performed to evaluate the independent risk factors. The predictive value of different models was compared by calculating the areas under the receiver operating characteristic (ROC) curve. Results: On-admission levels of CLR in patients with poor outcomes (6 months mRS 3-6), CVS, DCI, and CH were significantly higher than those in patients with good outcomes (6 months mRS 0-2), non-CVS, non-DCI, and non-CH. Multivariate logistic regression analysis revealed that admission CLR was independently associated with CVS (OR [95% CI] 2.116 [1.507-2.971]; p < 0.001), and DCI (OR [95% CI] 1.594 [1.220-2.084]; p = 0.001). In ROC analysis, the area under the curve (AUC) of CLR for poor outcomes (6 months mRS 3-6), CVS, DCI, and CH prediction were (AUC [95% CI] 0.639 [0.555-0.724]; p = 0.002), (AUC [95% CI] 0.834 [0.767-0.901]; p < 0.001), (AUC [95% CI] 0.679 [0.581-0.777]; p < 0.001), and (AUC [95% CI] 0.628 [0.543-0.713]; p = 0.005) revealing that admission CLR had a favorable predictive value for CVS after aSAH. The sensitivity and specificity of admission CLR for CVS prediction were 77.1% and 75.4%. On-admission CLR of 0.757 mg × 10-6 was identified as the best cutoff threshold to discriminate between CVS and non-CVS (CVS: CLR < 0.757 mg × 10-6 11/100 [11.0%] vs. CLR ≥ 0.757 mg × 10-6 37/66 [56.1%]; p < 0.001). Conclusions: High levels of on-admission CLR serve as an independent risk factor for CVS and DCI after aSAH. Admission CLR is an easy-to-quantify laboratory parameter that efficiently predicts the CVS after aSAH, which can provide some guidance for clinicians to evaluate for possible progression and treatment strategies in patients with aSAH.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and pallets-to-lymphocyte ratio (PLR) are currently validated as cheap and accessible biomarkers in different types of solid tumors, including head and neck cancers (HNC).
OBJECTIVE: To evaluate the possible purposes and biomarker value of NLR, PLR, and MLR recorded pre-treatment (radiotherapy/chemotherapy) in HNC.
METHODS: From 190 patients with HNC included in the oncology records in the oncology outpatient clinic of the Craiova County Emergency Hospital (from January 2002 to December 2022), 39 cases met the inclusion criteria (squamous cell carcinoma and the possibility to calculate the pre-treatment (chemotherapy/radiotherapy) value of NLR, PLR, and MLR. Overall survival (OS) values were correlated with NLR, PLR, and MLR.
RESULTS: The median values for NLR, PLR, and MLR were 6.15 (1.24-69), 200.79 (61.3-1775.0), and 0.53 (0.12-5.5), respectively. In the study, the mean values for NLR, PLR, and MLR of 2.88, 142.97, and 0.36, respectively, were obtained. The median OS in the study group was 11 months (1-120). Although a negative Pearson\'s correlation was present, the relationship between the variables was only weak, with values of R = 0.07, p = 0.67, R = 0.02, p = 0.31, and R = 0.07, p = 0.62 being related to NLR, PLR, and MLR, respectively, in correlation with OS. The median values of NLR, PLR, and MLR were calculated (1.53, 90.32, and 0.18, respectively) for the HNC cases with pre-treatment values of NLR < 2 and for the HNC cases with NLR values ≥ 6 (23.5, 232.78, and 0.79, respectively). The median OS for cases with NLR < 2 and NLR ≥ 6 were 17.4 and 13 months, respectively.
CONCLUSIONS: The comparative analysis of the data highlights a benefit to OS for cases low values of NLR. The role of not only borderline NLR values (between 2 and 6) as a prognostic marker in HNSCC but also the inclusion of PLR and MLR in a prognostic score must also be defined in the future. Prospective studies with more uniformly selected inclusion criteria could demonstrate the value of pre-treatment NLR, PLR, and MLR for treatment stratification through the intensification or de-escalation of non-surgical curative treatment in HNSCC.

Spinal Muscular Atrophy is a genetic neuromuscular disease that leads to muscle weakness and atrophy and it is characterized by the loss of α-motor neurons in the spinal cord\'s anterior horn cells. The disease appears due to low levels of the survival motor neuron protein. There are continuing clinical trials for the treatment of Spinal Muscular Atrophy. Quinazoline-based compounds are promising since they were tested on fibroblasts derived from the patients and found to increase the survival motor neuron protein levels. In this study, using multiple linear regression, we generated robust and valid quantitative structure- activity relationship models to predict the survival motor neuron-2 promoter activity of the new candidate compounds using the experimental survival motor neuron-2 promoter activity values of 2,4-diaminoquinazoline derivatives taken from the literature. The novel compounds designed by combining the pyrido[1,2-α]pyrimidin-4-one moeity of the known drug Risdiplam with that of 2,4 - diaminoquinazoline scaffold were predicted to exhibit strong promoter activities.

BACKGROUND: We aimed to investigate the relationship between monocyte/lymphocyte ratio (MLR) and monocyte/high-density lipoprotein ratio (MHR) with abdominal aortic calcification (AAC) in patients on peritoneal dialysis (PD).
METHODS: The time-averaged (TA) of relevant indexes and AAC scores (AACs) of 160 eligible patients were measured.
RESULTS: Patients divided into the new AAC (n = 57) and the other without (n = 82). High TA-MLR (OR = 110.537, p = 0.018) and long duration of dialysis (OR = 1.045, p < 0.001) were independent risk factors of the new AAC. Patients divided into the no AAC (n = 82), the moderate-to-severe AAC (n = 26), and the mild AAC (n = 52). High TA-MLR (OR = 42.649, p = 0.032), high age at starting PD (OR = 1.055, p < 0.001), and long duration of PD (OR = 1.036, p < 0.001) were independent risk factors of AAC severity.
CONCLUSIONS: MLR is an independent risk factor for the occurrence and severity of AAC and its value for the assessment of AAC is better than MHR.

Objective: To explore the influence factors of poor prognosis of esophageal squamous cell carcinoma (ESCC) and the predictive value of inflammatory reaction indexes including neutrophils and lymphocytes ratio (NLR), platelet and lymphocyte ratio (PLR), monocyte and lymphocyte ratio (MLR) provision and differentiation degree, infiltration depth, lymph node metastasis number on the postoperative recurrence of ESCC. Methods: A total of 130 patients with ESCC who underwent radical resection from February 2017 to February 2019 in Nanyang Central Hospital were selected and divided into good prognosis group (66 cases) and poor prognosis group (64 cases) according to the prognostic effect. The clinical data and follow-up data were collected. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor prognosis. Spearman correlation analysis was used to determine the correlation between preoperative NLR, PLR and MLR with the degree of differentiation, depth of invasion and number of lymph node metastases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of NLR, PLR and MLR in predicting poor prognosis of ESCC. Results: Univariate analysis showed that the degree of differentiation, the degree of invasion and the number of lymph node metastasis were related to the prognoses of patients with ESCC (P<0.05). Multivariate logistic regression analysis showed that the degree of differentiation, depth of invasion and number of lymph node metastases were independent influencing factors for poor prognosis of patients with ESCC, moderate differentiation (OR=2.603, 95% CI: 1.009-6.715) or low differentiation (OR=9.909, 95% CI: 3.097-31.706), infiltrating into fibrous membrane (OR=14.331, 95% CI: 1.333-154.104) or surrounding tissue (OR=23.368, 95% CI: 1.466-372.578), the number of lymph node metastases ≥ 3 (OR=9.225, 95% CI: 1.693-50.263) indicated poor prognosis. Spearman correlation analysis showed that NLR was negatively correlated with the degree of differentiation and the number of lymph node metastases (r=-0.281, P=0.001; r=-0.257, P=0.003), PLR was negatively correlated with the degree of differentiation, depth of invasion and number of lymph node metastasis (r=-0.250, P=0.004; r=0.197, P=0.025; r=-0.194, P=0.027), MLR was positively correlated with the degree of differentiation and the number of lymph node metastasis (r=0.248, P=0.004; r=0.196, P=0.025). ROC curve analysis showed that the areas under the curve of NLR, PLR and MLR in predicting poor prognosis of ESCC were 0.971, 0.925 and 0.834, respectively. The best cut-off value of NLR was 2.87. The sensitivity and specificity of NLR in predicting poor prognosis of ESCC were 90.6% and 87.9%, respectively. The optimal cut-off value of PLR was 141.75. The sensitivity and specificity for predicting poor prognosis of ESCC were 92.2% and 87.9%, respectively. The best cut-off value of MLR was 0.40. The sensitivity and specificity of MLR in predicting poor prognosis of esophageal squamous cell carcinoma were 54.7% and 100.0%, respectively. Conclusions: The degree of differentiation, the degree of invasion and the number of lymph node metastases are closely related to the poor prognosis of patients with esophageal squamous cell carcinoma. NLR, PLR and MLR can provide important information for predicting the poor prognosis of esophageal squamous cell carcinoma.
目的： 探讨食管鳞状细胞癌预后不良的影响因素及中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、单核细胞与淋巴细胞比值(MLR)与分化程度、浸润深度、淋巴结转移数目等炎性反应指标对食管鳞状细胞癌术后复发的预测价值。 方法： 选取2017年2月至2019年2月在南阳市中心医院行根治术治疗的130例食管鳞状细胞癌患者，按照预后效果分为预后良好组(66例)和预后不良组(64例)。收集其临床资料和随访资料。采用多因素logistic回归分析确定患者预后不良的独立影响因素，采用Spearman相关分析明确术前NLR、PLR和MLR与分化程度、浸润深度、淋巴结转移数目的相关性，采用受试者工作特征(ROC)曲线分析评价NLR、PLR和MLR预测食管鳞状细胞癌预后不良的效能。 结果： 单因素分析显示，分化程度、浸润程度、淋巴结转移数目与食管鳞状细胞癌患者的预后有关(均P<0.05)。多因素logistic回归分析显示，分化程度、浸润深度和淋巴结转移数目均为食管鳞状细胞癌患者预后不良的独立影响因素，中分化(OR＝2.603，95% CI：1.009~6.715)或低分化(OR＝9.909，95% CI：3.097~31.706)、浸润到纤维膜(OR＝14.331，95% CI：1.333~154.104)或周围组织(OR＝23.368，95% CI：1.466~372.578)、淋巴结转移数目≥3枚(OR＝9.225，95% CI：1.693~50.263)的患者患者预后不良。Spearman相关分析显示，NLR与分化程度、淋巴结转移数目呈负相关(r＝－0.281，P＝0.001；r＝－0.257，P＝0.003)，PLR与分化程度、浸润深度、淋巴结转移数目呈负相关(r＝－0.250，P＝0.004；r＝－0.197，P＝0.025；r＝－0.194，P＝0.027)，MLR与分化程度、淋巴结转移数目呈正相关(r＝0.248，P＝0.004；r＝0.196，P＝0.025)。ROC曲线分析显示，NLR、PLR和MLR预测食管鳞状细胞癌预后不良的曲线下面积分别为0.971、0.925和0.834。NLR的最佳界值为2.87，预测食管鳞状细胞癌预后不良的灵敏度为90.6%，特异度为87.9%。PLR的最佳界值为141.75，预测食管鳞状细胞癌预后不良的灵敏度为92.2%，特异度为87.9%。MLR的最佳界值为0.40，预测食管鳞状细胞癌预后不良的灵敏度为54.7%，特异度为100.0%。 结论： 分化程度、浸润程度、淋巴结转移数目与食管鳞状细胞癌预后不良密切相关，NLR、PLR和MLR能为食管鳞状细胞癌预后不良预测提供重要信息。.

In this study, we investigated PFAS (per- and polyfluoroalkyl substances) binding potencies to nuclear hormone receptors (NHRs): peroxisome proliferator-activated receptors (PPARs) α, β, and γ and thyroid hormone receptors (TRs) α and β. We have simulated the docking scores of 43 perfluoroalkyl compounds and based on these data developed QSAR (Quantitative Structure-Activity Relationship) models for predicting the binding probability to five receptors. In the next step, we implemented the developed QSAR models for the screening approach of a large group of compounds (4464) from the NORMAN Database. The in silico analyses indicated that the probability of PFAS binding to the receptors depends on the chain length, the number of fluorine atoms, and the number of branches in the molecule. According to the findings, the considered PFAS group bind to the PPARα, β, and γ only with low or moderate probability, while in the case of TR α and β it is similar except that those chemicals with longer chains show a moderately high probability of binding.

Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cut-off value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males (59%) and 202 females (41%); 161 patients (33%) had a right-sided, 202 (42%) a left-sided primary, and 122 (25%) a rectal tumor. Interestingly, gender was associated with MLR (p = 0.004) and sidedness (p = 0.006). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. According to univariate analysis of the training set, MLR (HR 9.07, p ≤ 0.001), MLR > 0.27 in females (HR 1.95, p = 0.003), and MLR > 0.49 in males (HR 2.65, p = 0.010) were associated with poorer OS, which was also confirmed in the validation set. In multivariate analysis, MLR > 0.27 in females (HR 2.77, p = 0.002), MLR > 0.49 in males (HR 5.39, p ≤ 0.001), BRAF mutation (HR 3.38, p ≤ 0.001), and peritoneal metastases (HR 2.50, p = 0.003) were still independently associated with worse OS. Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable Independent prognostic factor. Further prospective studies are needed to confirm these data.