BackgroundMigraine is a common chronic neurological disease， and patent foramen ovale （PFO） has been closely associated with migraine. Current research primarily focuses on the pathological mechanism and the therapeutic effects of interventional closure， with limited attention paid to the impact of PFO on sleep quality in migraine patients. ObjectiveTo compare the difference in sleep quality between PFO-positive and PFO-negative migraine patients， and to analyzes influencing factors of sleep quality in PFO-positive migraine patients， so as to provide references for clinical interventions to improve sleep quality in PFO-positive migraine patients. MethodsA total of 673 migraine patients who met the diagnostic criteria of migraine in the International Classification of Headache Disorders， third edition （ICHD-3）， and all patients underwent contrast-enhanced transcranial Doppler （c-TCD） and transthoracic echocardiographic right heart contrast echocardiography （cTTE） in the Third Hospital of Mianyang from January 2020 to October 2024. Basic demographic data were collected using a self-designed questionnaire， headache severity was assessed with the Visual Analogue Scale （VAS）， and sleep quality was invaluated using the Pittsburgh Sleep Quality Index （PSQI）. PFO patients was diagnosed through c-TCD combined with c-TTE. Binary logistic regression analysis was employed to examine the influencing factors of sleep quality in PFO-positive migraine patients. ResultsA total of 673 （100.00%） migraine patients were enrolled， including 223 PFO-positive cases （33.14%） and 450 PFO-negative cases（66.86%）. The PFO-positive group showed significantly more severe headache severity （χ²=15.799， P<0.01） and poorer sleep quality （χ²=14.377， P<0.01） compared with PFO-negative group. PFO-positive patients demonstrated significantly higher barrier factor scores of sleep quality， sleep latency， sleep efficiency， sleep disturbance， hypnotic medication use， and daytime dysfunction compared with PFO-negative counterparts （t=3.634， 3.269， 2.785， 3.428， 2.907， 3.637， Bonferroni adjust P<0.05/7=0.007）.By contrast， no significant difference was noted in sleep duration scores between the two groups（t=2.349， Bonferroni adjust P>0.05/7=0.007）.The Binary Logistic regression analysis revealed that age （OR=1.021， 95% CI： 1.001~1.041）， headache severity （OR=6.030， 95% CI： 4.085~8.901）， and PFO grade （OR=1.893，95% CI： 1.288~2.784）were significant influencing factors for sleep quality in migraine patients with PFO. ConclusionMigraine patients with PFO-positive exhibited poorer sleep quality compared wtih PFO-negative patients. Older age， higher headache servity， and more severe PFO grade are identified as risk factors for impaired sleep quality in PFO-positive migraine patients.

Objective To investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α(RORA)in the proliferation and progression of colorectal cancer(CRC)cells.Methods The expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR,FISH,and IHC.Cell proliferation capability was detected through EdU and CFSE assay,cell apoptosis by flow cytometry assay,and cell migration and invasion abilities by cell scratch and Transwell invasion assays,respectively.The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay,cell function rescue test,RT-PCR,and Western blot assay.Finally,bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation,invasion,and progression of CRC via regulating RORA.Results miR-18a-5p exhibited a high expression in CRC tissues and cells(P<0.05)and promoted the proliferation,migration,and invasion of CRC cells(P<0.05).In addition,RORA served as the target gene of miR-18a-5p,and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells(P<0.05).The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A.Conclusion The targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC.The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC,which can be a potential therapeutic target for CRC.

Objective: To analyze the association between the self-rated health (SRH) status and risk of cardiovascular disease (CVD) among the middle-aged and eldly Chinese. Methods: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which enrolled 21 133 participants by using the probability proportional to size (PPS) sampling from 150 counties/districts of 28 provinces in China from 2011 to 2012. A total of 11 701 participants were included in the study. Basic information and SRH were obtained in the baseline survey via questionnaires. Information of CVD was self-reported during the follow-up. Cox proportional hazards modeling was used to analyze the association between the baseline SRH and risk of CVD. Subgroup analyses were performed by age, sex and body mass index (BMI), and their interactions with SRH for risk of CVD were examined by using the likelihood ratio test. A sensitivity analysis was conducted to test the robustness of the association. Results: Participants were (57.9±9.7) years old, and men accounted for 48.1% (5 626). SRH was reported as the excellent, very good, good, fair and poor among 4.2% (n=487), 13.5% (n=1 583), 33.6% (n=3 932), 35.4% (n=4 147) and 13.3% (n=1 552), respectively. During 42 104 person-years of followed up, 590 cases of CVD were identified. Cox regression analyses showed that compared with the excellent/very good SRH, the HR (95%CI) of CVD risk for the good, fair and poor SRH was 1.36 (1.02-1.80), 1.66 (1.26-2.19) and 1.89 (1.38-2.59), respectively. Subgroup analyses showed that compared with the excellent/very good SRH, HR (95%CI) of CVD risk for poor SRH in the group of 45-59 years old, equal to or over 75 years old, men, women and normal BMI were 2.00 (1.32-3.04), 3.87 (1.04-14.46), 1.76 (1.07-2.91), 1.92 (1.27-2.91) and 2.30 (1.42-3.72), respectively. There were no interactions between age, sex, BMI and SRH (P>0.05). Conclusion SRH is associated with risk of CVD among middle-aged and elderly Chinese. The CVD risk for good, fair and poor SRH is higher than that for excellent/very good SRH.

Intestinal mucosal barrier is the first line of defense against exogenous substances. A complete mechanical barrier can separate the body from the contents of the intestines and prevent the translocation of bacteria and microorganisms in the intestines, playing an important role in maintaining the homeostasis of the human body. If the intestinal mechanical barrier function is damaged, it will cause the intestinal endotoxin and bacterial translocation, leading to systemic inflammatory response syndrome and multiple organ dysfunction diseases. The barrier function of intestinal mucosa is a key link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, the maintenance of intestinal mucosal barrier function is of great value for the diagnosis and treatment of NAFLD. In this paper, the research progress in intestinal mechanical barrier function of NAFLD was reviewed, and the main factors maintaining intestinal permeability of NAFLD were introduced, such as apoptosis, autophagy, apical junctional complex, cytoskeleton, main signal pathway, to provide reference for the diagnosis and treatment of NAFLD.

γδ T cells have been well recognized as a unique cell population that is actively involved in both innate and adoptive immunity of bodies. The features of γδ T cells, such as their major histocompatibility complex independent antigen recognition and their cytotoxic effects to tumor cells, make them as promising candidates used for cancer immunotherapy. There is a strong interest in developing γδ T cell-based immunotherapy for clinical application in treating cancer patients. This review discusses the progress of recent studies related to the γδ T cells and cancer immunotherapy, with an emphasis on the main characteristics of γδ T cells in several types of gynecologic tumors.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

Objective To investigate the effect and molecular mechanism of the combination of mechanical strain stimulation and icariin (ICA) on inhibiting the differentiation of osteoclasts induced by fatigue load stimulation. Methods The mouse mononuclear macrophage cell line RAW264.7 was cultured in vitro, and the blank control group was α-MEM complete medium. In the fatigue load group, RAW264.7 cells were treated with 5000 μεmechanical stretch strain, and then cultured in an osteoclast culture medium that was an α-MEM complete medium containing 40 ng/ml macrophage colony-stimulating factor and 40 ng/ml osteoclast differentiation factor. In the mechanical stimulation + ICA group, RAW264.7 cells were treated as the same procedure in the fatigue load group, and then cultured in an α-MEM complete medium containing 1 ×10 -5 mol/L ICA simultaneously with a 1000 μεtensile strain on the substrate. The activity of tartrate-resistant acid phosphatase (TRAP) was detected using a TRAP assay kit. The mRNA expression of the osteoclast marker genes, i.e. TRAP, cathepsin K(CTSK) and matrix metalloproteinase 9 (MMP-9) was detected by real-time RT-PCR. The nuclear translocation of nuclear factor kappa B (NF-κB) was analyzed by Western Blot. Results Compared with the fatigue load group, the combination of mechanical stimulation (1000 με substrate stretching) and ICA (1×10-5 mol/L) could significantly inhibit the activity of TRAP in osteoclasts (P<0.01) and reduce osteoclastosis. Moreover, that combination not only could down-regulate the mRNA expression of TRAP, CTSK and MMP-9 and the differences were statistically significant (all P<0.01), but also could inhibit the formation of osteoclasts by inhibiting the phosphorylation of P65, P50 and IκB-α in NF-κB signaling pathway. Conclusions The coupling of mechanical stimulation and ICA can effectively inhibit the osteoclast differentiation and the bone resorption induced by fatigue load, and the mechanism may involve regulating NF-κB signaling pathway.

Adaboost algorithm with improved K-nearest neighbor classifiers is proposed to predict protein subcellular locations. Improved K-nearest neighbor classifier uses three sequence feature vectors including amino acid composition, dipeptide and pseudo amino acid composition of protein sequence. K-nearest neighbor uses Blast in classification stage. The overall success rates by the jackknife test on two data sets of CH317 and Gram1253 are 92.4% and 93.1%. Adaboost algorithm with the novel K-nearest neighbor improved by Blast is an effective method for predicting subcellular locations of proteins.

Objective To analyze the cognitive changes and influencing factors in patients with lacunar cerebral infarction after carotid artery intervention therapy. Methods Sixty lacunar cerebral infarction combined with carotid stenosis patients treated with artery intervention therapy (intervention therapy group) and 68 lacunar cerebral infarction without carotid stenosis patients treated with drug therapy (drug therapy group) were selected. The neuropsychological test was completed at entry and 1, 6, 12 months after entry, and the results were compared with 60 healthy controls (control group). The cognitive changes were observed. The neuropsychological test included mini mental state examination (MMSE), Montreal cognitive assessment scale (MoCA) and cognitive field test. Results There were statistical differences in other scores except the Stroop test C section and Wechsler adult intelligence scale (WAIS-RC) picture arrangement subtest at entry in intervention therapy group and drug therapy group compared with control group (P<0.05). There were no statistical differences in the all scores at entry between drug therapy group and intervention therapy group (P>0.05). In intervention therapy group, the MMSE scores, MoCA total score, Rey-Osterrieth complex figure test (ROCFT), auditory verb learning test (AVLT), and the WAIS-RC picture arrangement subtest, verbal fluency test, WAIS-RC digit span backwards subtest of performing function 12 months after entry were significantly better than those at entry, and there were statistical differences (P<0.05). MMSE score, MoCA total score, long-time delayed recall of ROCFT, the immediate recall, long-time delayed recall and short delayed recall of AVLT, semantic category fluency test of performing function and digit span backwards subtest of WAIS-RC 6 months after entry were significantly better than those at entry:(27.8 ± 2.2) scores vs. (26.4 ± 1.9) scores, (20.7 ± 2.3) scores vs. (19.3 ± 2.0) scores, (12.4 ± 3.2) scores vs. (10.8 ± 2.6) scores, (54.3 ± 10.6) scores vs. (49.9 ± 10.9) scores, (12.4 ± 2.0) scores vs. (11.2 ± 2.8) scores, (12.9 ± 2.0) scores vs. (10.6 ± 2.6) scores, (17.5 ± 4.0) scores vs. (15.4 ± 3.4) scores and (4.0 ± 0.9) scores vs. (3.5 ± 0.9) scores, and there were statistical differences (P<0.05). In drug therapy group, there were no statistical differences in the all scores 1 and 6 months after entry, compared with that at entry (P>0.05);the MMSE score, MoCA total score, ROCFT, the immediate recall, long-time delayed recall and short delayed recall of AVLT, WAIS-RC picture arrangement subtest, verbal fluency test, WAIS-RC digit span backwards subtest of performing function and digit span backwards subtest of WAIS-RC 12 months after entry were significantly better than those at entry, and there were statistical differences (P<0.05). There were no statistical differences in all scores 12 months after entry between intervention therapy group and drug therapy group (P>0.05). In patients intervention therapy group, Logistic regression analysis showed that the MoCA score was related with age, hypertension and low education level (P<0.01 or<0.05), but was not related with smoking, diabetes and interventional treatment (P>0.05). Conclusions Cognitive impairment in patients with lacunar cerebral infarction and carotid stenosis is severe and extensive, but most cognition disorders can improve to normal level 12 months after artery intervention therapy.

Objective To compare the efficacy,toxicity and prognosis on treating advanced non-small-cell lung cancer (NSCLC) between using weekly docetaxel (DOC) and using DOC associated with nedaplatin(NDP).Methods 56 cases of NSCLC patients were retrospectively analyzed.Group A included 34 cases who were treated with weekly DOC (35 mg/m2,dl,8).Group B included 22 cases who were treated with DOC associated with NDP (DOC 35 mg/m2,dl,8,NDP 80 mg/m2,d2).One treatment cycle was 21 days.Efficacy,toxicity and prognosis were evaluated after 2 treatment cycles.Results RR of group A was 8.8 ％ (3/34).RR of group B was 27.3 ％ (6/22).DCR of group A was 50.0 ％ (17/34).DCR of group B was 63.6 ％ (14/22).PFS of group A was 2.3 months.PFS of group B was 5.1 months.OS of group A was 8.7 months.OS of group B was 10.5 months.1-year survival rate of group A was 26.5 ％.1-year survival rate of group B was 31.8 ％.The above comparisons were not statistically different (all P ＞ 0.05).In adverse reactions,hematologic toxicity in group B was greater than that in group A (x2 =4.877,P =0.027).Other adverse reactions such as gastrointestinal reactions,fatigue and so on were grade Ⅰ-Ⅱ.Conclusions The treatment of weekly DOC used in advanced NSCLC is safe,effective an low toxicity.There are no significant difference of RR and PFS between single DOC and DOC associated with NDP.