Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for EGFR-mutant nonsmall cell lung cancer (NSCLC) patients. However, studies have reported that not all NSCLC patients harboring kinase domain mutations in epidermal growth factor receptor (EGFR) show significant clinical benefits from EGFR-targeted tyrosine kinase inhibitors (TKIs). Therefore, it is necessary to establish feasible biomarkers to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs. This study aimed to determine biomarkers using inflammatory parameters from complete blood counts to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs.We retrospectively investigated 127 stage IIIB/IV NSCLC patients with activating EGFR mutations who were treated with EGFR-TKIs. We used receiver operating characteristic (ROC) curves to determine the optimal cut-off for the inflammatory markers as prognostic factors. Additionally, univariate and multivariate analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS) of EGFR-mutant NSCLC patients treated with EGFR-TKIs.The receiver operating characteristic analysis indicated that the lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) cut-off values were 3.37 and 2.90, respectively. The univariate analysis showed that a high LMR (>3.37) and low NLR (≤2.90) were significantly correlated with long-term PFS and OS (LMR, P = .007; NLR, P < .001). The multivariate Cox regression analysis revealed that only low NLR was an independent prognostic factor for long-term PFS and OS (PFS, HR = 0.573, 95% CI: 0.340-0.964, P = .036; OS, HR = 0.491, 95% CI: 0.262-0.920, P = .026).The data show that a low NLR was a good prognostic factor in EGFR-mutant NSCLC patients receiving EGFR-TKIs treatment. Moreover, the NLR measurement has better prognostic value than LMR.

Knee osteoarthritis (KOA) is one of the leading causes of disability. The effectiveness of auricular point pressing therapy for treating KOA remains controversial. This protocol describes the method of a systematic review and meta-analysis evaluating the effectiveness and safety of auricular point pressing therapy for treating KOA.

Increasing evidence observed in clinical phenotypes show that abrupt breathing disorders during sleep may play an important role in the pathogenesis of sudden unexplained nocturnal death syndrome (SUNDS). The reported Brugada syndrome causing mutation R1512W in cardiac sodium channel α subunit encoded gene SCN5A, without obvious loss of function of cardiac sodium channel in previous in vitro study, was identified as the first genetic cause of Chinese SUNDS by us. The R1512W carrier was a 38-year-old male SUNDS victim who died suddenly after tachypnea in nocturnal sleep without any structural heart disease. To test our hypothesis that slight acidosis conditions may contribute to the significant loss of function of mutant cardiac sodium channels underlying SUNDS, the biophysical characterization of SCN5A mutation R1512W was performed under both extracellular and intracellular slight acidosis at pH 7.0. The cDNA of R1512W was created using site-directed mutagenesis methods in the pcDNA3 plasmid vector. The wild type (WT) or mutant cardiac sodium channel R1512W was transiently transfected into HEK293 cells. Macroscopic voltage-gated sodium current (INa) was measured 24 hours after transfection with the whole-cell patch clamp method at room temperature in the HEK293 cells. Under the baseline conditions at pH 7.4, R1512W (-175 ± 15 pA/pF) showed about 30% of reduction in peak INa compared to WT (-254 ± 23 pA/pF, P < 0.05). Under the acidosis condition at pH 7.0, R1512W (-130 ± 17 pA/pF) significantly decreased the peak INa by nearly 50% compared to WT (-243 ± 23 pA/pF, P < 0.005). Compared to baseline condition at pH 7.4, the acidosis at pH 7.0 did not affect the peak INa in WT (P > 0.05) but decreased peak INa in R1512W (P < 0.05). This initial functional study for SCN5A mutation in the Chinese SUNDS victim revealed that the acidosis aggravated the loss of function of mutant channel R1512W and suggested that nocturnal sleep disorders-associated slight acidosis may trigger the lethal arrhythmia underlying the sudden death of SUNDS cases in the setting of genetic defect.

Comparing the clinical and radiographic outcomes in anterior cervical discectomy and fusion (ACDF) using a zero-profile anchored spacer (ROI-C) or a conventional cage-plate construct (CPC) for treating noncontiguous bilevel of cervical degenerative disc disease (CDDD).Overall, 46 patients with 2 noncontiguous segments of CDDD, treated with ACDF from January 2011 to October 2015, were included in this study. ROI-C was used in 22 patients (group A) and CPC in 24 patients (group B). The clinical and radiographic outcomes and complications were compared pre- and postoperatively. All patients were followed up for at least 24 months after surgery.No significant difference was found in fusion rate, cervical curvature, height of fused segment (FSDH), intraoperative blood loss, and Japanese Orthopaedic Association (JOA), and Neck Disability Index (NDI) scores between the 2 groups. Group A had a shorter operation time and significantly lower incidence of dysphagia (3 and 24 months postoperatively) than group B (P < .001 and P < .05, respectively). Moreover, group A had a higher loss of FSDH than group B, but with no difference between the 2 groups (P > .05). Two cages developed subsidence in group A (4.5%) and 2 adjacent levels developed degeneration in group B (2,8%).ACDF with ROI-C device was superior to CPC for noncontiguous bilevel of CDDD because it avoided postoperative dysphagia and required a shorter operation time. Moreover, the clinical outcomes were comparable. Prospective trials with larger samples and longer follow-up are required to confirm the results.

The objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus cyclophosphamide (CTX)-corticosteroid combination therapy in idiopathic membranous nephropathy (IMN) patients.

This study aimed to use network pharmacology to predict the therapeutic mechanism of oroxyli semen (OS) on triple-negative breast cancer (TNBC) and validate it through in vitro experiments.

Numerous studies have shown that lymphovascular invasion (LVI) is linked to biochemical recurrence (BCR) in prostate cancer (PCa) patients following radical prostatectomy (RP). However, the actual clinicopathological impacts of LVI remain unclear. Thus, we performed a meta-analysis to evaluate the pathologic and prognostic impacts of LVI in PCa patients.

The proinflammatory effects of IL12p40 had been documented in the literature, and anti-IL12p40 treatment had been proved to be effective in therapy of Crohn disease (CD) in a phase 2b clinical trial. However, the precise role of IL12p40 in the pathogenesis of inflammatory bowel disease (IBD) was still poorly understood. In this study, we investigated the expressions of IL12p40 and its receptor interleukin-12 receptor β 1 both locally and systemically in IBD cases and healthy controls, and the contribution of IL12p40 in IBD pathogenesis. We found that the expression of IL12p40 was elevated both at messenger RNA and protein levels systematically and locally in IBD patients but more significantly in CD patients. Our genetic association study revealed that the polymorphisms of IL12B rs6887695 were associated with both CD and ulcerative colitis (UC) susceptibility in Chinese population, but did not affect the serum IL12p40 level in either CD patients or UC patients. In addition, CD4⁺ T cells isolated from peripheral blood of CD patients secreted the most abundant IL12p40 production, compared with the UC patients and healthy controls. We also found for the first time that neutralizing IL12p40 secretion could inhibit proliferation, enhance apoptosis, induce a G0/G1 arrest, restrain T helper 1 type immune responses, and promote chemokine C-C motif ligand 20-mediated migration of human CD4⁺ T cells, which might be the mechanisms why anti-IL12p40 treatment presented efficacy in CD.

The intestinal microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD), and geographical and genetic backgrounds impact the composition of the intestinal microbiota. However, there is a lack of evidence regarding the overall changes and characteristics of fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) in Chinese patients with IBD. We recruited 26 patients with Crohn's disease (CD), 46 patients with ulcerative colitis (UC), and 21 healthy individuals; we collected matched fresh fecal and mucosal samples from the same subjects. The microbial communities were studied by 454-pyrosequencing. Community-wide changes in FAM and MAM were observed in patients with IBD. The proportion of several butyrate-producing bacteria, such as of the genera Roseburia, Coprococcus, and Ruminococcus were significantly reduced, whereas the pathogens Escherichia-Shigella and Enterococcus were prevalent in patients with IBD. FAM and MAM were similar between CD and UC. FAM differed from MAM in healthy individuals and patients with UC. In conclusion, the compositions of FAM and MAM were altered in patients with IBD. The reduction of butyrate-producing bacteria and the increase in opportunistic pathogens might be associated with the pathogenesis of IBD.

Traumatic brain injury (TBI), due to its high mortality and morbidity, is an important research topic. Apoptosis plays a pathogenic role in a series of neurological disorders, from neurodegenerative diseases to acute neurological lesions.In this study, we analyzed the association between apoptosis and the Glasgow Outcome Scale (GOS), to examine the potential of apoptosis as a biomarker for a TBI outcome. Patients with severe TBI were recruited at the Department of Neurosurgery, Wujin Hospital Affiliated with Jiangsu University, between January 2018 and December 2019. As a control group, healthy subjects were recruited. The concentrations of caspase-3, cytochrome c, sFas, and caspase-9 in the cerebrospinal fluid (CSF) were analyzed by enzyme-linked immunosorbent assay (ELISA). The association between the GOS and the clinical variables age, sex, initial Glasgow Coma Scale (GCS) score, intracranial pressure (ICP), cerebral perfusion pressure (CPP), initial computed tomography (CT) findings, and apoptotic factors was determined using logistic regression. The area under the receiver operator characteristic (ROC) curve (AUC), and thus the sensitivity and specificity of each risk factor, were obtained.The levels of caspase-3, cytochrome c, sFas, and caspase-9 in the TBI group were significantly higher than those in the control group (P < .05). The logistic regression results showed that ICP and caspase-3 were significant predictors of outcome at 6 months post-TBI (P < .05). The AUC was 0.925 and 0.888 for ICP and caspase-3, respectively. However, the AUC for their combined prediction was 0.978, with a specificity and sensitivity of 96.0% and 95.2%, respectively, showing that the combined prediction was more reliable than that of the 2 separate factors.We demonstrated that caspase-3, cytochrome C, sFas, and caspase-9 were significantly increased in the CSF of patients following severe TBI. Furthermore, we found that ICP and caspase-3 were more reliable for outcome prediction in combination, rather than separately.