Evaluation of the diagnostic performance of colposcopy in the detection of cervical high-grade squamous intraepithelial lesions among women with transformation zone type 3.

BACKGROUND: Inaccurate colposcopy diagnosis may lead to inappropriate management and increase the incidence of cervical cancer. This study aimed to evaluate the diagnostic accuracy of colposcopy in the detection of histologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with transformation zone type 3 (TZ3). METHODS: Records from 764 patients with TZ3 who underwent colposcopy-directed biopsy and/or endocervical curettage in Putuo Hospital China between February 2020 and March 2023 were retrospectively collected. Colposcopy was carried out based on 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) and Colposcopy nomenclature. The diagnostic performance of colposcopy for identifying CIN2 + was evaluated compared with biopsies. The Kappa and McNemar tests were used to perform statistical analyses. RESULTS: Among the study population, 11.0% had pathologic CIN2+. The relative sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of colposcopy for histologic CIN2 + were 51.2%, 96.5%, 64.2% and 94.1%, respectively. The senior colposcopists (80.6%) had a higher colposcopic accuracy to diagnose histologic CIN2 + than junior colposcopists (68.6%). In subgroup analyses, age group ≥ 60 years (70.3%) showed lowest diagnostic accuracy when compared with age groups of < 45 years (84.4%) and 45-59 years (74.9%). CONCLUSION: Our findings suggest an increased risk of diagnostic inaccuracy of colposcopy in identifying CIN2 + in those ≥ 60 years of age with TZ3, and the accuracy of colposcopy is required to be further improved.

Mechanism Exploration of Environmental Pollutants on Premature Ovarian Insufficiency: a Systematic Review and Meta-analysis.

As a public health problem, premature ovarian insufficiency leads to infertility or sub-fertility. In addition to premature ovarian insufficiency (POI) increases the lifetime risk of bone fragility, cardiovascular disease, and cognitive impairment. To investigate the effects of environmental pollutants on the occurrence of POI and explore its mechanism, we conducted a computer search for articles published in electronic databases by December 13, 2022. Three reviewers independently examined all included studies and scored the qualities of included studies using the Newcastle-Ottawa Scale criteria. In this meta-analysis, eight clinical studies as well as ten preclinical findings showed a pooled OR of 2.331 and 95% CI of 1.968-2.760. This confirms that environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI. In addition, it is demonstrated from the results of this study that signaling pathway of calcium and PI3K Akt and Xpnpep2, Col1, Col3, Col4, Cx43, Egr3, Tff1, and Ptgs2 genes may all be involved in the process. Environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI.

Inhibition of EphA4 reduces vasogenic edema after experimental stroke in mice by protecting the blood-brain barrier integrity.

Cerebral vasogenic edema, a severe complication of ischemic stroke, aggravates neurological deficits. However, therapeutics to reduce cerebral edema still represent a significant unmet medical need. Brain microvascular endothelial cells (BMECs), vital for maintaining the blood-brain barrier (BBB), represent the first defense barrier for vasogenic edema. Here, we analyzed the proteomic profiles of the cultured mouse BMECs during oxygen-glucose deprivation and reperfusion (OGD/R). Besides the extensively altered cytoskeletal proteins, ephrin type-A receptor 4 (EphA4) expressions and its activated phosphorylated form p-EphA4 were significantly increased. Blocking EphA4 using EphA4-Fc, a specific and well-tolerated inhibitor shown in our ongoing human phase I trial, effectively reduced OGD/R-induced BMECs contraction and tight junction damage. EphA4-Fc did not protect OGD/R-induced neuronal and astrocytic death. However, administration of EphA4-Fc, before or after the onset of transient middle cerebral artery occlusion (tMCAO), reduced brain edema by about 50%, leading to improved neurological function recovery. The BBB permeability test also confirmed that cerebral BBB integrity was well maintained in tMCAO brains treated with EphA4-Fc. Therefore, EphA4 was critical in signaling BMECs-mediated BBB breakdown and vasogenic edema during cerebral ischemia. EphA4-Fc is promising for the treatment of clinical post-stroke edema.

Safety, immunogenicity and immune-persistence of heterologous prime-boost immunization with BBIBP-CorV and ZF2001 against SARS-CoV-2 in healthy adults aged 18 years or older.

BACKGROUND: Because SARS-CoV-2 mutations and immunity wane over time, a third dose of heterologous COVID-19 vaccine is proposed for individuals primed with inactivated COVID-19 vaccine. RESEARCH DESIGN AND METHODS: We conducted a single-center, open-label trial to assess the safety, immunogenicity, and immune-persistence of a heterologous BBIBP-CorV/ZF2001 prime-boost vaccination in Chinese adults. 480 participants who had been primed with two doses of BBIBP-CorV, received a third dose of ZF2001 after an interval of 3-4, 5-6, or 7-9 months. RESULTS: The overall incidence of adverse reactions within 30 days after vaccination was 5.83%. No serious adverse reactions were reported. The respective geometric mean titers (GMTs) of neutralizing antibodies for 3-4, 5-6, and 7-9 months groups at baseline were 2.06, 2.02, and 2.10; which increased to 55.42, 63.45, and 62.06 on day 14; then decreased to 17.53, 23.79, and 26.73 on day 30; before finally waning to 8.29, 9.24, and 9.51 on day 180. After the booster, the three groups showed no significant differences in GMTs. GMTs were lower in older participants than younger participants. CONCLUSIONS: A heterologous BBIBP-CorV/ZF2001 prime-boost vaccination was safe and immunogenic. Prime-boost intervals did not affect the immune response. The immune response was weaker in older adults than younger adults. CLINICAL TRIAL IDENTIFIER: NCT05205083.

Detection of cervical high-grade squamous intraepithelial lesions and assessing diagnostic performance of colposcopy among women with oncogenic HPV.

BACKGROUND: HPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China. METHODS: This cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included. RESULTS: Univariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54-26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56-13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12-3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P<0.001). Among women with low-grade cytology, 24.1% had CIN2+, and the risks for HPV16/18 (58.2%) were higher than for other HR-HPV(16.8%). For those with high-grade cytology, there was no significant difference between HPV groups ( 75.0% vs. 72.9%, P > 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable. CONCLUSIONS: The results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+.

Quantitative assessment of biceps brachii muscle stiffness by using Young's modulus-Angle curve during passive stretching in stroke patients.

Purpose: This study aims to use shear wave elastography (SWE) to dynamically describe the characteristics of biceps brachii muscle stiffness during passive stretching in healthy participants, investigate changes in the Young's modulus-angle curve under various states of muscle tone in stroke patients, and develop a new method for measuring muscle tone quantitatively. Methods: In total, 30 healthy volunteers and 54 stroke patients were evaluated for elbow flexor muscle tone on both sides using passive motion examination and were divided into groups based on their muscle tone status. The real-time SWE video of the biceps brachii and the Young's modulus data were recorded during the passive straightening of the elbow. The Young's modulus-elbow angle curves were created and fitted using an exponential model. The parameters yielded from the model were subjected to further intergroup analysis. Results: The repeatability of the Young's modulus measurement was generally good. During passive elbow extension, the Young's modulus of the biceps brachii steadily increased as muscle tone increased, and it increased faster when the modified Ashworth scale (MAS) score got higher. The exponential model's fitness was generally good. The curvature coefficient was significantly different between the MAS 0 group and the hypertonia groups (MAS 1, 1+, and 2 groups). Conclusion: The passive elastic characteristics of the biceps brachii are consistent with the exponential model. The Young's modulus-elbow angle curve of the biceps brachii changes in distinct ways depending on the muscle tone status. SWE can be used to quantify muscular stiffness during passive stretching as a new way of muscle tone evaluation, allowing for quantitative muscle tone evaluation and mathematical assessment of muscle mechanical properties in stroke patients.

Evaluation of antibody kinetics and durability in healthy individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China.

Background: Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. Methods: We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. Results: Our results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89)-17.8% (16/90). Conclusions: Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The inactivated vaccine booster can reverse the decrease of antibody levels to prime strain, but it does not elicit potent neutralization against Omicron; therefore, the optimization of booster procedures is vital. Funding: Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation.

Hypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia.

Therapeutic hypothermia at 32-34 °C during or after cerebral ischaemia is neuroprotective. However, peripheral cold sensor-triggered hypothermia is ineffective and evokes vigorous counteractive shivering thermogenesis and complications that are difficult to tolerate in awake patients. Here, we show in mice that deep brain stimulation (DBS) of warm-sensitive neurones (WSNs) in the medial preoptic nucleus (MPN) produces tolerable hypothermia. In contrast to surface cooling-evoked hypothermia, DBS mice exhibit a torpor-like state without counteractive shivering. Like hypothermia evoked by chemogenetic activation of WSNs, DBS in free-moving mice elicits a rapid lowering of the core body temperature to 32-34 °C, which confers significant brain protection and motor function reservation. Mechanistically, activation of WSNs contributes to DBS-evoked hypothermia. Inhibition of WSNs prevents DBS-evoked hypothermia. Maintaining the core body temperature at normothermia during DBS abolishes DBS-mediated brain protection. Thus, the MPN is a DBS target to evoke tolerable therapeutic hypothermia for stroke treatment.

Deep Learning in Prediction of Late Major Bleeding After Transcatheter Aortic Valve Replacement.

PURPOSE: Late major bleeding is one of the main complications after transcatheter aortic valve replacement (TAVR). We aimed to develop a risk prediction model based on deep learning to predict major or life-threatening bleeding complications (MLBCs) after TAVR. PATIENTS AND METHODS: This was a retrospective study including TAVR patients from West China Hospital of Sichuan University Transcatheter Aortic Valve Replacement Registry (ChiCTR2000033419) between April 17, 2012 and May 27, 2020. A deep learning-based model named BLeNet was developed with 56 features covering baseline, procedural, and post-procedural characteristics. The model was validated with the bootstrap method and evaluated using Harrell's concordance index (c-index), receiver operating characteristics (ROC) curve, calibration curve, and Kaplan-Meier estimate. Captum interpretation library was applied to identify feature importance. The BLeNet model was compared with the traditional Cox proportional hazard (Cox-PH) model and the random survival forest model in the metrics mentioned above. RESULTS: The BLeNet model outperformed the Cox-PH and random survival forest models significantly in discrimination [optimism-corrected c-index of BLeNet vs Cox-PH vs random survival forest: 0.81 (95% CI: 0.79-0.92) vs 0.72 (95% CI: 0.63-0.77) vs 0.70 (95% CI: 0.61-0.74)] and calibration (integrated calibration index of BLeNet vs Cox-PH vs random survival forest: 0.007 vs 0.015 vs 0.019). In Kaplan-Meier analysis, BLeNet model had great performance in stratifying high- and low-bleeding risk patients (p < 0.0001). CONCLUSION: Deep learning is a feasible way to build prediction models concerning TAVR prognosis. A dedicated bleeding risk prediction model was developed for TAVR patients to facilitate well-informed clinical decisions.

Surface enhanced Raman scattering-based lateral flow immunosensor for sensitive detection of aflatoxin M1 in urine.

Aflatoxin M1 (AFM1) is generally used as a biomarker in urine for the assessment of aflatoxin exposure in humans and animals. However, there is no approach for the rapid and on-site monitoring of AFM1 level in urine. Here, we report a surface enhanced Raman scattering (SERS)-based lateral flow immunosensor built for such a purpose. Raman molecule 5,5-dithiobis-2-nitrobenzoic acid and anti-AFM1 monoclonal antibody were conjugated with Au (core)@Ag (shell) nanoparticle to serve as SERS nanoprobe. AFM1-bovine serum albumin was conjugated with gold nanoparticle and then applied onto nitrocellulose membrane as a visible "GOLD" test line. Quantitation of AFM1 was performed by the readout of Raman signal from the SERS nanoprobes captured on the test line. After optimizing experimental parameters, the detection limit of this immunosensor can achieve as low as 1.7 pg/mL of AFM1 in urine, which is far below the recommended tolerable level (30 pg/mL) of AFM1 in urine. The spiking experiment yielded 93.8%-111.3% recovery with coefficients of variation below 17% demonstrating high assay accuracy and precision. Moreover, this immunosensing assay is fast with an assay time below 20 min. Therefore, the developed immunosensor is a promising tool for the rapid assessment of aflatoxin exposure in the field.

Short-term dynamic changes in neutralizing antibodies against enterovirus 71 after vaccination.

BACKGROUND: Short-term dynamic changes in neutralizing antibodies against EV71 and EV71-IgM after inactivated EV71 vaccine injection are unknown. METHODS: This study was designed as a randomized, open-label study and was registered at ClinicalTrials.gov (NCT03278132). In total, 120 healthy infants aged 6-35 months were randomized 1:1:1 to provide a second blood sample on day 10, day 20, or day 30 after the first vaccine dose, respectively. RESULTS: According to the per-protocol set, a rapid immune response against EV71 was observed 10 days after the first EV71 vaccine dose, with antibody titers ≥1:8 in 89.19% of participants (95% CI: 74.58-96.97%) on day 10, in 80.65% (95% CI: 62.53-92.55%) on day 20, in 66.67% (95% CI: 49.03-81.44%) on day 30, and in 100% (95% CI: 96.52%-.) on day 60. Based on an ELISA, the percentages of participants positive for EV71-IgM on day 0 and day 60 were 1.71% (2 out of 117) and 82.86% (87 out of 105), respectively. CONCLUSIONS: The EV71 vaccine could be used for contingency vaccination to further control EV71-associated disease outbreaks. Caution should be taken in using the EV71-IgM test for rapid EV71 infection diagnosis after EV71 vaccine administration. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03278132.

Rapid one-step enzyme immunoassay and lateral flow immunochromatographic assay for colistin in animal feed and food.

BACKGROUND: Colistin (polymyxin E) is a kind of peptide antibiotic which has been approved in animal production for the purposes of disease prevention, treatment, and growth promotion. However, the wide use of colistin in animal feed may accelerate the spread of colistin-resistance gene MCR-1 from animal production to human beings, and its residue in animal-origin food may also pose serious health hazards to humans. Thus, it is necessary to develop corresponding analytical methods to monitor the addition of colistin in animal feed and the colistin residue in animal-origin food. RESULTS: A one-step enzyme-linked immunosorbent assay (ELISA) and a lateral flow immunochromatographic assay (LFIA) for colistin were developed based on a newly developed monoclonal antibody. The ELISA showed a 50% inhibition value (IC50) of 9.7 ng/mL with assay time less than 60 min, while the LFIA had a strip reader-based detection limit of 0.87 ng/mL in phosphate buffer with assay time less than 15 min. For reducing the non-specific adsorption of colistin onto sample vial, the components of sample extraction solution were optimized and proved to greatly improve the assay accuracy. The spiked recovery experiment showed that the recoveries of colistin from feed, milk and meat samples were in the range of 77.83% to 113.38% with coefficient of variations less than 13% by ELISA analysis and less than 18% by LFIA analysis, respectively. Furthermore, actual sample analysis indicated that the two immunoassays can produce results consistent with instrumental analysis. CONCLUSIONS: The developed assays can be used for rapid qualitative or quantitative detection of colistin in animal feed and food.

Expression level of ACOT7 influences the prognosis in acute myeloid leukemia patients.

BACKGROUND: ACOT plays an important role in lipid metabolism and recent studies found that ACOT participates in some kinds of tumorigenesis. However, both the role of ACOT and its significance have not been revealed in AML. Therefore, we conduct this study in order to investigate the association between AML and ACOT, and hopefully contributed to the management of AML. METHODS: One hundred and fifty-six AML patients were enrolled in our study whose data were derived from the Cancer Genome Atlas database. There were 85 patients who received only chemotherapy and other 71 patients underwent allo-HSCT. RESULTS: Patients in high ACOT7 group had a significant lower EFS and OS, while patients in high versus low expression levels of other types of ACOT showed no significant difference on the outcome. High level of ACOT7 related with poor outcome in both chemotherapy-only group and HSCT group. CONCLUSIONS: High expression level of ACOT7 indicates unfavorable outcome in AML patients. Allo-HSCT could not overcome the unfavorable effect of ACOT7 in these patients.

Transcriptomic Responses in the Livers and Jejunal Mucosa of Pigs under Different Feeding Frequencies.

Feeding frequency in one day is thought to be associated with nutrient metabolism and the physical development of the body in both experimental animals and humans. The present study was conducted to investigate transcriptomic responses in the liver and jejunal mucosa of pigs to evaluate the effects of different feeding frequencies on the body's metabolism. Twelve Duroc × Landrance × Yorkshire growing pigs with an average initial weight (IW) of 14.86 ± 0.20 kg were randomly assigned to two groups: feeding one time per day (M1) and feeding two times per day (M2); each group consisted of six replicates (pens), with one pig per pen. During the one-month experimental period, pigs in the M1 group were fed on an ad libitum basis at 8:00 am; and the M2 group was fed half of the standard feeding requirement at 8:00 am and adequate feed at 16:00 pm. The results showed that average daily feed intake, average daily gain, feed:gain, and the organ indices were not significantly different between the two groups (p > 0.05). The total cholesterol (T-CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) concentrations in the serum, and the TG concentration in the liver in the M2 groups were significant lower than those in the M1 group, while the T-CHO concentration in the liver were significant higher in the M2 group (p < 0.05). Jejunal mucosa transcriptomic analysis showed the gene of Niemann-Pick C1-Like 1 (NPC1L1), Solute carrier family 27 member 4 (SLC27A4), Retinol binding protein 2 (RBP2), Lecithin retinol acyltransferase (LRAT), Apolipoprotein A (APOA 1, APOA 4, APOB, and APOC 3) were upregulated in the M2 group, indicating that fat digestion was enhanced in the small intestine, whereas Perilipin (PLIN1 and PLIN2) were downregulated, indicating that body fat was not deposited. Fatty acid binding proteins (FABPs) and Acetyl-CoA acyltransferase 1 (ACAA1) were upregulated in the M2 group, indicating that two times feeding daily could promote the oxidative decomposition of fatty acids. In conclusion, under the conditions in this study, the feeding frequency had no significant effect on the growth performance of pigs, but affected the body's lipid metabolism, and the increase of feeding frequency promoted the fat digestion in the small intestine and the oxidative decomposition of fatty acids in the liver.

High Expression Levels of ACTN1 and ACTN3 Indicate Unfavorable Prognosis in Acute Myeloid Leukemia.

Background: Actinins are major cytoskeletal proteins that mediate sarcomere function, and they also have important non-muscle functions such as regulating cytokinesis, cell adhesion and migration. There are four isoforms of actinins in mammals (ACTN1-4). Recently, the relationship between actinins and cancer has been discovered in many types of malignancy, yet their prognostic significance in acute myeloid leukemia (AML) remains unclear. Methods: We collected data of 155 de novo AML patients from The Cancer Genome Atlas (TCGA) database; 85 patients received chemotherapy only and 70 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We divided each treatment groups into sub-groups based on the median expression levels of ACTN1-4. Results: Survival analysis showed that in the chemotherapy-only group, high ACTN1 and ACTN3 expression were associated with shorter event-free survival (EFS) and overall survival (OS) (p<0.01). Multivariate analysis suggested that high expression of ACTN1 and ACTN3 (p<0.05) were independent poor prognostic factors. In the allo-HSCT group, ACTN1-4 expression had no impact on survival. Conclusions: Our study suggested that high expression levels of ACTN1 and ACTN3 adversely affected the survival of AML patients, but their harmful impact could be overcome by allo-HSCT.

MicroRNA-425 upregulation indicates better prognosis in younger acute myeloid leukemia patients undergoing chemotherapy.

The aim of the present study was to investigate whether the expression levels of microRNA-425 (miR-425) were associated with the prognosis of acute myeloid leukemia (AML) in patients treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 162 AML patients were enrolled and divided into chemotherapy and allo-HSCT groups. Next, the overall survival (OS) and event-free survival (EFS) were compared between patients with high and low miR-425 expression in each of the treatment groups. In the chemotherapy group, high miR-425 expression was favorable for EFS (P=0.001) and OS (P=0.001) in younger patients (<60 years), whereas it had no effect on EFS and OS in older patients (≥60 years). In the allo-HSCT group, there was no association between miR-425 expression levels and clinical outcomes. Further analyses suggested that in the low miR-425 expression group, EFS and OS were longer in patients treated with allo-HSCT as compared with those treated with chemotherapy (both P<0.001), whereas no significant differences were observed in the high miR-425 expression group. In conclusion, the current data indicated that miR-425 is an independent favorable prognostic factor for younger AML patients undergoing chemotherapy, and its use may facilitate clinical decision-making in selecting treatment for AML patients. Patients with low miR-425 expression may benefit from allo-HSCT, whereas allo-HSCT did not appear to be beneficial in patients with high miR-425 expression.

High expression of microRNA-500 is associated with poor prognosis in patients with acute myeloid leukemia receiving allogeneic hematopoietic stem cell transplantation.

MicroRNA-500 (miR-500) is a potential prognostic biomarker in a number of different types of cancer, such as prostate cancer and hepatocellular carcinoma. This study aimed to explore the clinical implications of miR-500 expression status in patients with acute myeloid leukemia (AML) that had received allogeneic hematopoietic stem cell transplantation (allo-HSCT). miR-500 expression status and clinical data were obtained from 74 patients with AML in the The Cancer Genome Atlas database receiving allo-HSCT. Patients with low expression level of miR-500 (miR-500low) were significantly more likely to present with a French-American-British classification M2 subtype (P=0.003), and less likely to have the M5 subtype (P=0.040) compared with patients with high expression levels (miR-500high). miR-500low patients were associated with low-risk AML (P=0.003) and core-binding factor subunit b-myosin heavy chain 11 translocation mutation (P=0.021). There was a significant difference in nucleophosmin 1 (P=0.009), NRAS proto-oncogene GTPase/KRAS proto-oncogene GTPase (P=0.047) and PHD finger protein 6 (P=0.040) expression levels between the two groups. miR-500high patients had a decreased overall survival (OS) time compared with the low expression group (P=0.035). Multivariate analysis revealed that miR-500 expression significantly affected OS time independent of other classical prognostic factors, such as age and common mutations. The analysis of survival curves further substantiated this result. The results obtained in the current study suggested that miR-500 may be a suitable prognostic marker for patients with AML receiving allo-HSCT.

High expression of dedicator of cytokinesis 1 adversely influences the prognosis of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.

Background: Overexpression of dedicator of cytokinesis 1 (DOCK1) has been confirmed as an unfavorable prognostic marker in acute myeloid leukemia (AML). Purpose: This study is to explore the clinical implications of DOCK1 on AML patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and methods: We analyzed 71 de novo AML patients treated with allo-HSCT and divided them into two groups (DOCK1 high vs DOCK1 low) by the median expression level of DOCK1. Results: High DOCK1 expression was associated with older age (P=0.019), wild-type CEBPA (P=0.002), IDH1/2 mutations (P=0.010) and RUNX1 mutation (P=0.005). Univariate analyses showed that DOCK1 high and RUNX1 mutation were associated with shorter OS (P<0.001, P=0.024). Multivariate analysis confirmed the negative effect of high DOCK1 level on overall survival (P=0.010). Conclusion: Our results demonstrate that in AML patients who received allo-HSCT, high DOCK1 expression might have a persistent negative prognostic impact post-transplant.

ssExpression level of GAS6-mRNA influences the prognosis of acute myeloid leukemia patients with allogeneic hematopoietic stem cell transplantation.

As high expression level of growth arrest-specific 6 (GAS6) had an adverse effect on prognosis in acute myeloid leukemia (AML) patients, it is interesting to reveal the relationship between GAS6-mRNA level and the survival condition of AML patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). We screened The Cancer Genome Atlas database and found 71 AML patients with GAS6-mRNA expression and received allo-HSCT treatments. We divided them into two groups based on the median expression of GAS6-mRNA. Patients with GAS6-mRNAhigh (n=36) seemed to have lower bone marrow (BM) blast (P=0.022), lower percentage of type M5 (P=0.034), lower percentage of inv(16)/CBFß-MYH11 karyotype (P=0.020), and lower rate of good risk classification (P=0.005) than the group GAS6-mRNAlow (n= 35). Higher expression level of GAS6-mRNA also brought higher RUNX1 mutations (P=0.003), MLL-PTD mutations (P=0.042), TP53 mutations (P=0.042), and lower NRAS/KRAS mutations (P=0.042). Univariate analyses showed that GAS6-mRNA was unfavorable for overall survival (OS) (P=0.044), as RUNX1 and WT1 also gave negative influences. Multivariate analyses confirmed that GAS6-mRNA cut down the event-free servival (EFS) and OS of AML patients with HSCT (P=0.029, P=0.025). Our study indicated that higher expression of GAS6-mRNA related with adverse effects in AML patients with HSCT treatment.

High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy.

The SMAD family (SMAD1-9) was critically important for regulating cellular process through transforming growth factor-ß signaling pathway, and contributed to carcinogenesis; however, their prognostic roles in acute myeloid leukemia (AML) remained unclear. This study collected 84 de novo AML patients treated with chemotherapy and 71 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Kaplan-Meier survival estimate indicated that among SMAD1-9, high SMAD3 and SMAD7 expression were both associated with poor event-free survival (EFS) and overall survival (OS; all P < 0.05) in AML patients undergoing chemotherapy; and high SMAD6 expression was associated with shorter EFS and OS (all P < 0.01) in patients underwent allo-HSCT. Multivariate analysis showed that only high SMAD7 expression had adverse effect on EFS and OS (P = 0.021, 0.026) independently. Furthermore, High SMAD3 and SMAD7 expressers had significantly shorter EFS and OS than low expressers (P = 0.006, 0.001). In AML patients who went through allo-HSCT, there were no significant differences for EFS and OS between patients with high and low-expression SMAD3 or SMAD7. Our study suggested that high expression of SMAD3 and SMAD7 predicted adverse prognosis in AML patients undergoing chemotherapy and SMAD7 was a better prognostic marker than SMAD3. Their prognosis impact may be overcome by allo-HSCT.