Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials & methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.
The sagittal imbalance (SI) of spine triggers compensatory mechanisms (CMs) of lower extremity (LE) to restore trunk balance. These CMs can cause long-period stress on the femur and may possibly alter the femoral morphology. This cross-sectional observational study aimed to answer the following questions: (a) Do SI subjects exhibit greater femoral bowing compared to subjects with sagittal balance? (b) Are there associations between femoral bowing and CMs of LE in SI subjects?
China is considered a country of low HIV prevalence (780,000 people living with HIV), however, HIV infections among high-risk populations continue to grow at alarming rates. Voluntary Counseling and Testing services were first implemented in 2003, and oral rapid HIV testing (ORHT) began in 2012. Dentists, as oral health experts, would be well placed to conduct ORHT. We assessed willingness of dentists to undertake ORHT in their clinical practice.A cross-sectional, paper-based survey of dentists from the Xi'an region of China was conducted from April to June 2013. Dentists were recruited from Shaanxi Stomatological Association using a stratified sampling methodology. A 40-item survey was used to measure knowledge of HIV, attitudes toward people living with HIV and willingness to conduct ORHT.477 dentists completed the survey with a mean HIV knowledge test score of 13.2/18 (SD 1.9). If made available in the dental setting, 276 (57.9%) preferred to use blood to diagnose HIV, only 190 (39.8%) preferred saliva or both. Four hundred and thirty-five (91.2%) thought that ORHT was needed in dental clinics. Female dentists felt more accepting of ORHT than males (93.8% vs. 87.8%; χ2=5.145; p<0.05). 42.6% of the participants who responded thought that lack of education on ORHT for dentists was the most urgent problem to solve for ORHT, 144 (31.3%) thought that lack of support for ORHT from patients was the most urgent problem. There was statistically significant difference among dental hospital, dentistry and department of dentistry (χ2=24.176; p<0.05).The majority of Chinese dentists thought that ORHT was needed in the dental setting. Providing opportunities for dentists and dental students to learn about HIV testing guidelines and practices is needed as well as feasibility and implementation science research.
Background: Screening for colorectal carcinoma (CRC) lacks an efficient, inexpensive and noninvasive approach. The stable presence of serum miRNA is expected to become a new diagnostic marker. Materials & methods: Based on 135 CRC patients and 135 normal controls, this study was conducted in three phases to identify suitable serum miRNA for CRC diagnosis by using quantitative reverse transcription PCR. Bioinformatic assays were used for target genes prediction and functional annotation. Results: Serum expression level of seven miRNAs were significantly different between CRC patients and the normal controls. The final diagnostic panel (area under the curve = 0.893; sensitivity = 81.25%, specificity = 73.33%) consists of miR-203a-3p, miR-145-5p, miR-375-3p and miR-200c-3p. Conclusion: The four-miRNA panel may serve as a novel, noninvasive biomarker for CRC diagnosis and screening.
Hepatic fibrosis (HF) is a common pathological complication of liver cirrhosis which affects human health. It is well established that microRNAs (miRNAs) regulate the proliferation, activation and apoptosis of hepatic stellate cells (HSCs).To determine the function and molecular mechanism of miR-340-5p/secreted phosphoprotein 1 (SPP1) axis in HF and identify potential therapeutic targets.The HF model in cholestatic rats was induced by ligating the common bile duct. The histological sections of the liver tissues were stained with hematoxylin and eosin (H&E), Masson's trichrome or Sirius Red. The differential expression of mRNAs in the liver tissues was examined using the microarray analysis. The expression levels of miR-340-5p, SPP1, alpha-smooth muscle actin (α-SMA), Collagen I, phosphorylated Smad2 (p-Smad2), and p-Smad3 were determined using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation was quantified using cell counting kit-8 (CCK-8) assays. The regulatory effect of miR-340-5p on SPP1 was determined with fluorescent reporter assay.The bile duct ligation (BDL) rat model was successfully induced, and SPP1 was upregulated in liver tissue from the BDL group compared to that of the sham group. The expression level of miR-340-5p was decreased in activated human primary normal fibroblasts (NFs) and activated LX-2 cells, and the mRNA and protein expression levels of SPP1 were increased in activated LX-2 cells. The SPP1 was the target of miR-340-5p, and the overexpression of SPP1 increased the proliferation of LX-2 cells, the expression of HF markers α-SMA and Collagen I, and key factors p-Smad2 and p-Smad3 (all p < 0.05). However, reverse results were obtained with the overexpression of miR-340-5p in LX-2 cells.Our findings provide evidence that SPP1 targeted by miR-340-5p promotes LX-2 cell proliferation and activation through the TGF-β1/Smads signaling pathway. Therefore, miR-340-5p and SPP1 may be possible therapeutic targets for HF.
Previous studies have shown that the miR-17-92 cluster is involved in the occurrence and development of bladder cancer. However, the role of serum miR-17-92 cluster in the diagnosis of bladder cancer has not been studied. In the present study, we evaluated the expression of miR-17-92 cluster members in bladder cancer tissues by analyzing 428 cases from TCGA database. Next, we collected the sera of 74 bladder cancer patients and 90 controls, and used qRT-PCR to detect the relative expression of the cluster. The results showed that the expression of the cluster members in the sera of patients were significantly higher than that of the controls, and they were positively correlated with the clinical stage and pathological grade of the patients. We evaluated their ability to diagnose bladder cancer using ROC, of which miR-92a-3p (AUC = 0.902), miR-17-5p (AUC = 0.845) and miR-20a-5p (AUC = 0.806) were the most prominent. Finally, we established a diagnostic model by logistic regression (AUC = 0.969). We further validated the results of the study using another dataset from the GEO database. Moreover, we evaluated the prognostic value of the cluster. The results revealed that miR-20a-5p was correlated with recurrence of bladder cancer. In summary, the present study validated the overexpression of serum miR-17-92 cluster in bladder cancer. The model composed of the three cluster members were confirmed to be a promising noninvasive biomarker for bladder cancer diagnosis.
To the Editor: Current guidelines recommend that for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT), preferably involving powerful P2Y12 receptor inhibitors, including ticagrelor or prasugrel, should be used for at least 12 months.[1–3] However, there is a lack of relevant evidence regarding the feasibility of de-escalation treatment and specific DAPT treatment regimens for ACS patient populations with high ischemic risk. From March 2017 to September 2021, 1335 ACS patients with Optimal Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) ischemia scores of at least 91 points and with a ≥12-month history of oral DAPT were identified at Langfang People's Hospital to explore the impact of a de-escalation treatment regimen, namely, replacing ticagrelor with clopidogrel or reducing the dosage of ticagrelor, on the prognosis of ACS patients at high risk of ischemia undergoing PCI. The study involving human participants were reviewed and approved by the Ethics Committee of Clinical Investigation, Langfang People's Hospital (No. 2023-YXLW-014). The exemption of informed consent has been approved by the medical ethics committee. According to the type and dosage of antiplatelet drugs, the study included 679 patients in the clopidogrel group, 469 patients in the ticagrelor group, 76 patients in de-escalation group 1, and 111 patients in de-escalation group 2. The patients in de-escalation group 1 were administered DAPT after PCI (aspirin 100 mg one time a day (qd) + ticagrelor 90 mg twice a day (bid)); dosage of ticagrelor was reduced to 60 mg bid at 3 months after PCI, and DAPT was continued for 9 more months. Ticagrelor was replaced with clopidogrel 75 mg qd at 3 months after PCI, and DAPT was continued for 9 more months for patients of de-escalation group 2. The patients in the clopidogrel group were administered DAPT after PCI (aspirin 100 mg qd + clopidogrel 75 mg qd) for 12 months. The patients in the ticagrelor group were administered DAPT after PCI (aspirin 100 mg qd + ticagrelor 90 mg bid) for 12 months. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during follow-up, including cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The primary safety end point was bleeding events, including major bleeding and minor bleeding defined by thrombolysis in myocardial infarction (TIMI).[4] The follow-up period was 12 months after PCI (the median follow-up duration was 38.32 months [17.72, 71.73]). The OPT-CAD scoring system was used in this study [Supplementary Table 1, https://links.lww.com/CM9/B891].[5] SPSS 26.0 software (IBM, Armonk, New York, USA) was used for statistical analysis. Measurement data with normal distribution are expressed as the mean ± standard deviation, and comparisons among the groups were analyzed by one-factor analysis of variance (ANOVA). Measurement data with non-normal distribution are expressed as median and interquartile interval, and comparisons among the groups were analyzed by the rank-sum test. Count data are expressed as frequencies and percentages, and the chi-squared test was used for analysis among the groups. Cox multivariate regression analysis was used to adjust the baseline data. Kaplan–Meier analysis was used to analyze the survival rate of the four groups of patients. Based on bilateral tests, P ≤0.008 indicated a statistically significant difference among the four groups. According to the baseline data, the age of the clopidogrel group (64.16 ± 8.54 years) was larger than that of the ticagrelor group (60.94 ± 9.30 years) (P <0.001) and de-escalation group 2 (61.05 ± 8.82 years) (P = 0.001) [Supplementary Table 2, https://links.lww.com/CM9/B891]. The proportion of unstable angina in the ticagrelor group (97/469 [20.7%]) was significantly smaller than that in the clopidogrel group (269/679 [39.6%]) and de-escalation group 2 (39/111 [35.1%]) (P <0.001, P = 0.001, respectively). The proportion of ST-segment elevation myocardial infarction (STEMI) patients in the ticagrelor group (341/469 [72.7%]) was significantly larger than that in the clopidogrel group (362/679 [53.3%]) and de-escalation group 2 (66/111 [59.5%]) (P <0.001, P = 0.006, respectively). The proportion of emergency PCI patients in the ticagrelor group (314/469 [67.0%]) was larger than that in de-escalation groups 1 (39/76 [51.3%]) and 2 (50/111 [45.0%]) and the clopidogrel group (306/679 [45.1%]) (P = 0.008, P <0.001, P <0.001, respectively). The proportion of high-risk patients with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) scores in the clopidogrel group (198/679 [29.2%]) was statistically significantly larger than that in the ticagrelor group (81/469 [17.3%]) and de-escalation group 2 (17/111 [15.3%]) (P <0.001; P = 0.002). According to the laboratory test results, the N-terminal proBNP level in de-escalation group 1 (393.00 [107.00, 450.00] ng/L) was lower than that in the clopidogrel group (465.00 [153.25, 1105.00] ng/L) and the ticagrelor group (569.00 [233.75, 1337.75] ng/L) (P = 0.005, P <0.001, respectively) [Supplementary Table 3, https://links.lww.com/CM9/B891]. The proportion of patients with ostial lesions in de-escalation group 2 (13/111 [11.7%]) was lower than that in the clopidogrel group (175/679 [25.8%]) and the ticagrelor group (120/469 [25.6%]) (P = 0.001, P = 0.002, respectively) [Supplementary Table 4, https://links.lww.com/CM9/B891]. The proportion of patients with diffused lesions in the clopidogrel group (324/679 [47.7%]) was statistically significantly higher than that in de-escalation group 2 (33/111 [29.7%]) (P <0.001). The incidence of in-stent restenosis in de-escalation group 1 (5/76 [6.6%]) was higher than that in the clopidogrel group (8/679 [1.2%]) (P = 0.003). The cox regression showed an increased incidence of MACCEs in the de-escalation group 2 compared with the clopidogrel group (hazard ratio [HR] = 2.359, 95% confidence interval [CI]: 1.233–4.512, P = 0.009), and patients with complete revascularization have a lower incidence of MACCEs (HR = 0.507, 95% CI: 0.311–0.829, P = 0.007) [Supplementary Table 5, https://links.lww.com/CM9/B891]. The incidence of MACCEs was significantly lower in the ticagrelor group (13/469 [2.8%]) than that in de-escalation group 2 (10/111 [9.0%]) (P = 0.003) [Supplementary Table 6, https://links.lww.com/CM9/B891]. The Kaplan–Meier curve showed that the incidence of MACCEs in both de-escalation groups did not significantly increase within 3 months after PCI (P = 0.651); the incidence of MACCEs in the ticagrelor group was significantly lower than that in de-escalation group 2 (P = 0.001) from the 3rd to 12th month after PCI, and there was no significant difference in bleeding risk among the four groups [Figure 1].Figure 1: (A) MACCE cumulative incidence. Cut-off point: 3 months after PCI. (B) Bleeding event cumulative incidence. Cut-off point: 3 months after PCI. (C) Major bleeding event cumulative incidence. Cut-off point: 3 months after PCI. MACCEs: Major adverse cardiovascular and cerebrovascular events; PCI: Percutaneous coronary intervention.The results confirmed that for ACS patients with a moderate or high risk of ischemia (with OPT-CAD ischemic scores ≥91), de-escalation to aspirin and ticagrelor 60 mg after 3 months increased the risk of MACCEs. In the TALOS AMI study, de-escalation from a powerful P2Y12 receptor inhibitor to clopidogrel one month after PCI was performed, and the results confirmed that de-escalation can reduce the incidence of bleeding events within one year (3.0% vs. 5.6%, P = 0.001) and did not increase the incidence of ischemic events (2.1% vs. 3.1%, P = 0.148).[6] However, the patients selected for that study were all patients who had no adverse events within one month after PCI. Our study had a relatively clear definition of high ischemic risk and a relatively complete evaluation system. The Kaplan–Meier curve suggested that intensive treatment with ticagrelor 90 mg reduced the occurrence of MACCEs and improved the prognosis of patients within one year after PCI. From the Kaplan–Meier curve we can conclude that although not statistically significant, de-escalation from ticagrelor 90 mg to ticagrelor 60 mg and initial application of clopidogrel showed an increase tendency of MACCEs, which reflects the advantage of intensive antiplatelet therapy with ticagrelor 90 mg in improving the prognosis of patients at high ischemic risk. In our study, some patients, especially those at high risk according to the ARC-HBR score, were administered the DAPT regimen of aspirin combined with clopidogrel after PCI. Although drug adjustments are consistent with the status of real-world retrospective cohort studies, active drug adjustments for high bleeding risk patients can also have an impact on the research results. The de-escalation of antiplatelet therapy is an individualized and optimized treatment for patients with CHD. The essence of this is the individualized evaluation of CHD patients and the maximization of drug benefits. A review of 21 related randomized controlled trials (RCTs) suggests that complete revascularization can reduce the incidence of MACCEs in patients with acute myocardial infarction,[7] which was similar to our outcome of the cox regression. It is suggested that for patients at high risk of ischemia with multiple vessel lesions, complete revascularization should be performed while fully evaluating the characteristics of the lesions. The limitations of this study were as follows: First, it was a retrospective study with a small sample size and short follow-up time, resulting in a low incidence of primary endpoint events, which affects the overall testing efficiency of this study. Second, for the standard group of patients who started using clopidogrel, the proportion of HBR-ARC high-risk patients was the highest, with statistical significance between groups. Active de-escalation based on high bleeding risk also affects the outcome of the final bleeding event. In conclusion, for ACS patients with high ischemic risk undergoing PCI, a de-escalation treatment regimen of clopidogrel at 3 months increased the incidence of ischemic events compared with an intensive treatment regimen of ticagrelor 90 mg, while there was no significant difference in the incidence of bleeding events. For such patients, 12 months of ticagrelor 90 mg intensive antiplatelet therapy could be considered. Funding This study was supported by the Self-financing Project of Lang Fang Science and Technology Research and Development Plan (Nos. 2022013038 and 2020013106), and Guiding Project of Hebei Medical Science Research Program (No. 20232053). Conflicts of interest None.
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