Percutaneous nephrostomy catheter-related infections in patients with gynaecological cancers: a multidisciplinary algorithmic approach.

BACKGROUND: Percutaneous nephrostomy catheters (PCNs) are commonly utilized in patients with gynaecological cancers due to intrinsic or extrinsic urinary obstruction. Unfortunately, these foreign medical devices may be associated with several infectious complications, including: pyelonephritis, renal abscess, and bacteraemia, which may lead to further delay of life-saving cancer therapy. AIM: To evaluate the performance of our multidisciplinary algorithm for diagnosis and treatment of PCN-related infections (PCNIs) and identify risk factors for recurrent urinary device-related infections. METHODS: Patients with gynaecological cancers having PCNIs were prospectively evaluated at our institution from July 2019 to September 2021. All patients were managed by our standardized algorithm and followed-up until reinfection or routine PCN exchange. FINDINGS: Of 100 consecutive patients with PCNIs, 74 had adequate follow-up, and were analysed in three groups according to clinical outcome: reinfection with the same organism (26%), reinfection with a different organism (23%), and no reinfection (51%). Their median age was 54 years, and the most common cancers were cervical (65%), and ovarian (19%) with 53% being metastatic. The most frequently recovered micro-organisms were Pseudomonas (32%), Enterococcus (27%), and Escherichia (24%) species. The main risk factors for recurrent PCNI with the same organism were pelvic radiation therapy (P=0.032), pelvic fistulas (P=0.014), and a PCNI with the same pathogen within the previous year (P = 0.012). CONCLUSIONS: Our algorithm has allowed for accurate diagnosis, staging, and treatment of and identification of several key risk factors for recurrent PCNIs. These results may lead to further preventive measures for these infections.

[Clinical analysis of chronic eosinophilic pneumonia in 9 cases].

Objective: To investigate the clinical features, treatment and prognosis of chronic eosinophilic pneumonia. Methods: Nine patients with chronic eosinophilic pneumonia diagnosed in Shandong Provincial Qianfoshan Hospital from January 2014 to December 2020 were enrolled and followed up. The data of clinically proven chronic eosinophilic pneumonia were reviewed. Results: The 9 cases included one male and eight females, aged from 16 to 71 years (median 47 years). Among them, 5 cases were complicated with asthma, 1 case was complicated with allergic rhinitis, and 1 case had an allergic history of pollen. All the patients had cough, expectoration, chest tightness and wheezing, and a few had fatigue (3/9), fever (1/9) and chest pain (1/9). Single or multiple patchy high-density shadows (9/9), mediastinal lymphadenopathy (7/9), air bronchogram (2/9), and reticular shadow (1/9) were observed in chest CT. Peripheral eosinophils (EOS) and serum total IgE increased to varying degrees in the 9 patients. Meanwhile, the bronchoscopy of 5 cases showed elevated percentage of eosinophils in alveolar lavage fluid, and the lung biopsy of remaining 4 cases showed EOS infiltration in lung alveolar and interstitium. After receiving glucocorticoid therapy for 0.5 to 1 month, the clinical symptoms of all 9 patients had been improved and lung lesions on CT scans had been obviously absorbed. Four cases relapsed during follow-up. Conclusions: For patients especially women who have a history of allergy, elevated blood eosinophils and serum total IgE with pulmonary high-density shadow or consolidation, chronic eosinophilic pneumonia should be considered, and bronchoscopy or percutaneous lung biopsy is indicated for a definite diagnosis. Glucocorticoid therapy is effective, but the rate of recurrence is high.

[Effect and underling mechanism of 6% hydroxyethyl starch 130/0.4 on serum albumen in trauma orthopedic patients during operation].

Objective: To investigate the effect of 6% hydroxyethyl starch 130/0.4(HES) on protein in severe trauma orthopedic patients after acute hemodilution. Methods: Fourty-eight severe trauma patients who met the inclusion criteria were selected from June 2018 to December 2018 in Yantaishan Hospital, and were randomly divided into two groups (n=24): group A and group B. Group A was ringer's sodium lactate control group, and group B was HES treatment group. After the tracheal intubation, the patients of group A were infused with 10% blood volume of sodium lactate ringer at 0.5 ml·kg(-1)·min(-1), and the patients in group B were infused with 10% blood volume of HES at 0.5 ml·kg(-1)·min(-1). Total protein (TP), human serum albumin (HSA), numbers of circulating endothelium cells (CEC), C-reactive protein (CRP), and serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10 and IL-6 were measured immediately after acute hemodilution (T(0)), 24 hours (T(1)) and 48 hours (T(2)) after acute hemodilution. After infusion into human body, HES bond to HSA, and fluorescence spectroscopy was used to analyze the binding relationship between HES and HSA in order to further study the effects of HES on HSA. Results: The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group A were (38±5) g/L, (66±5) g/L, (5.5±0.4)/0.9 µl, (24±5) µg/L, (8.9±0.8) µg/L, (44±6) µg/L, (13.6±1.4) mg/L; While at T(1) were (33±5) g/L, (60±6) g/L, (10.2±0.7)/0.9 µl, (87±9) µg/L, (38.8±2.3) µg/L, (57±7) µg/L, (23.4±2.4) mg/L. The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group B were(38±4)g/L, (66±5) g/L, (5.4±0.6)/0.9 µl, (24±6) µg/L, (9.1±0.9) µg/L, (45±6) µg/L, (13.4±1.8) mg/L; While at T(1) were (35±5)g/L, (62±5)g/L, (7.4±0.6)/0.9 µl, (70±8) µg/L, (29.5±3.1) µg/L, (72±6) µg/L, (19.7±2.2) mg/L. HSA and TP decreased at T(1) in group A as compared with T(0) (P<0.05), contrarily CEC increased significantly at T(1), TNF-ɑ, IL-6, IL-10 and CRP augmented at T(1) and T(2) in two groups (P<0.05). In comparison with the patients of group A, CEC decreased significantly at T(1) (P<0.05). TNF-ɑ, IL-6, CRP reduced significantly at T(1) and T(2) (P<0.05), but IL-10 increased at T(1) and T(2) in group B (P<0.05). The secondary structure of HSA changed after HES was added in the HES solution. The fluorescence intensity of HSA decreased with the increase of HES concentration,which suggested that HES induced HSA fluorescence quenching. HES could bind to Trp-214 residue in HSA at a molecular ration of 1∶1. Conclusions: 6% HES reduces the occurrence of low protein level in severe trauma patients after operation. HES could bind to Trp-214 amino acid residue in HSA and form the complex at a molecular ratio of 1∶1. The formation of HES-HSA complex increases the volume of HES, avoids the vascular leakage, protects the vascular endothelial cells, and induces anti-inflammatory immunity in the patients with capillary syndrome.

[Prevalence of allergy in children with acute rhinosinusitis].

Objective:To explore the prevalence of allergy in patients with acute rhinosinusitis (ARS) and evaluate the severity of symptoms in ARS children with or without allergy.Method:Two hundred and seven children (4-12 years of age) with ARS and 85 children of control group were included in our research from June, 2016 to January, 2018. We use questionaire to collect the basic information of pediatric patients. The results of skin prick test (SPT) were recorded. Mothers were required to complete the Sinus and Nasal Quality-of-Life Survey (SN-5).All ARS childern were divided into allergic group and non-allergic group according to the result of SPT. We use binomial distribution to evaluate the population rate. t-test, Chi-square test and Wilcoxon rank-sum test were appropriately used to compare the parameters between two groups.Result:Among the 207 ARS participants in this study, 44.4% participants were shown to response to at least one Inhalation allergen and 40.6% participants were shown to response to at least one perennial allergen. Both ratios were significantly higher than those of the control group. Perennial allergy seems to be much more common than seasonal allergy in pediatric patients with ARS. The most troublesome symptoms among the participants with acute rhinosinusitis combined with allergic rhinitis were nasal obstruction (5.28±1.34), nasal discharge (5.07±1.04), post-nasal drip (4.63±1.31) and itchy eyes/nose (4.28±1.51). Four subscale scores of the SN-5 including nasal obstruction, allergy symptoms, emotional distress and activity limitation in the allergic group were obviously higher than those of the non-allergic group.Conclusion:Allergic factors play an important role in the pathogenesis of pediatric acute rhinosinusitis.

[Analysis of the related factors of attention deficit/hyperactivity disorder and allergic rhinitis in children].

Objective:To investigate the association between symptom of attention deficit/hyperactivity disorder (ADHD) and allergic rhinitis (AR) in children with AR at different sexes and different ages. Method:A total of 439 AR children aged 6 to 12 years were enrolled in this study. Basic information (age, gender, medical history, family history and comorbidities) of children with AR was collected. Results of prick tests on children skin were recorded. (TNSS) and Chinese version of the SNAP-Ⅳ scale, children under the guidance of independent completion of children's quality of life of children with nasal conjunctivitis scale (PRQLQ). According to the results of SNAP-Ⅳ, children were divided into AR with ADHD group ï¼»attention deficit and hyperactivity symptom score (IHS) >1.25ï¼½ and AR without ADHD group (IHS≤1.25). The differences between the two groups of children were analyzed using group t-test and χ² test, and the relationship between each parameter and IHS >1.25 was analyzed by binary logistic regression. Result:Using SPSS 22.0 software, among all the included AR children, IHS >1.25 children accounted for 26.4%, IHS >1.25 group AR symptom scores were significantly higher than HIS ≤1.25 groups. Univariate analysis showed that children with age, gender, duration of AR symptoms, skin index and PRQLQ subscales had a correlation with IHS >1.25. After controlling for age and gender, duration of AR symptoms and skin index correlated with IHS >1.25 The estimated OR values are 1.807 (95%CI: 1.350-2.419) and 1.912 (95%CI: 1.320-2.772), respectively. The estimated OR values of PRQLQ subscale and IHS >1.25 were 1.657 (nasal symptom score), 1.324 (eye symptom score), 2.48 (non-eye-nasal symptom score), 1.418 (Behavior problem score) and 2.045 (activity and sleep score). The correlation between IHS>1.25 and the skin index and PRQLQ subscales was mainly found in males with stratification of age and gender, and the association between duration of AR symptoms and HIS >1.25 was statistically significant among all groups reflected. Conclusion:The association between attention deficits and hyperactivity symptoms in AR children was correlated with the severity of AR symptoms, duration, and skin index, and this association was more pronounced in males. In children with AR and ADHD, early management of AR symptoms may improve their ADHD symptoms.

Risk of epilepsy in surgical patients undergoing general or neuraxial anaesthesia.

Limited information is available on the risks of epilepsy after surgery in patients receiving general or neuraxial anaesthesia. Using Taiwan's National Health Insurance Research Database, we identified 1,478,977 patients aged ≥ 20 years who underwent surgery (required general or neuraxial anaesthesia with hospitalisation for more than one day) between 2004 and 2011. We selected 235,066 patients with general anaesthesia and 235,066 patients with neuraxial anaesthesia using a frequency-matching procedure for age and sex. We did not study those with co-existing epilepsy-related risk factors. The adjusted rate ratios (RRs) and 95% confidence intervals (CIs) of newly diagnosed epilepsy 1 year after surgery associated with general anaesthesia were analysed in the multivariate Poisson regression model. The one-year incidence of postoperative epilepsy for patients with general anaesthesia and neuraxial anaesthesia were 0.41 and 0.32 per 1000 persons, respectively, and the corresponding RR was 1.27 (95%CI 1.15-1.41). The association between general anaesthesia and postoperative epilepsy was significant in men (RR = 1.22; 95%CI 1.06-1.40), women (RR = 1.33; 95%CI 1.15-1.55) and 20-39-year-old patients. The risk of postoperative epilepsy increased in patients with general anaesthesia who had co-existing medical conditions and postoperative complications.

The impact of a novel transendometrial approach for caesarean myomectomy on obstetric outcomes of subsequent pregnancy: a longitudinal panel study.

OBJECTIVE: To evaluate the obstetric and surgical outcomes of a novel transendometrial approach for myomectomy during caesarean section in subsequent pregnancies. DESIGN: Longitudinal panel study. SETTING: Chang Gung Memorial Hospital, Taiwan, with approximately 5000 births per annum. POPULATION: Pregnant women complicated with uterine myoma. METHOD: Sixty-three pregnant women who received transendometrial myomectomy during the first caesarean delivery reported a subsequent live pregnancy and planned an elective repeat caesarean delivery. MAIN OUTCOME MEASURES: Obstetric outcomes consisted of gestational age at birth, newborn weight, Apgar score, birthweight adequacy, uterine rupture, placental abruption, placenta praevia, placenta accreta, spontaneous preterm birth and preterm premature rupture of membranes. Surgical outcomes consisted of surgical time, blood loss, blood transfusion, postoperative fever, length of hospital stay and mean adhesion score. RESULT: The mean gestational age at birth and newborn weight at the subsequent caesarean section were superior to those at the first caesarean delivery. Spontaneous preterm birth, small-for-gestational-age infants and preterm premature rupture of membranes occurred more often in the first pregnancy than in the subsequent pregnancy. The mean surgical time was shorter for the subsequent caesarean delivery than for the first caesarean delivery combined with myomectomy. The other surgical composite outcomes of blood loss, blood transfusion, postoperative fever, length of hospital stay and mean adhesion score were similar across the two stages of caesarean deliveries. CONCLUSION: The novel transendometrial approach for caesarean myomectomy may improve the obstetric outcomes of subsequent pregnancy without causing any additional immediate and long-term adverse surgical outcomes. TWEETABLE ABSTRACT: Transendometrial caesarean myomectomy may improve future obstetric outcomes.

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.

Embryonic origin of primary colon cancer predicts survival in patients undergoing ablation for colorectal liver metastases.

BACKGROUND: In patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear. METHODS: We identified 74 patients with CLM who underwent percutaneous ablation during 2004-2015. Survival and recurrence after ablation of CLM from midgut origin (n = 18) and hindgut origin (n = 56) were analyzed. Prognostic value of embryonic origin was evaluated. RESULTS: Recurrence-free survival (RFS) and overall survival (OS) after percutaneous ablation were worse in patients from midgut origin (3-year RFS: 5.6% vs. 24%, P = 0.004; 3-year OS: 25% vs. 70%, P 0.001). In multivariable analysis, factors associated with worse OS were midgut origin (hazard ratio [HR] 4.87, 95% CI 2.14-10.9, P 0.001), multiple CLM (HR 2.35, 95% CI 1.02-5.39, P = 0.044), and RAS mutation (HR 2.78, 95% CI 1.25-6.36, P = 0.013). At a median follow-up of 25 months, 56 patients (76%) had developed recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin (P = 0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin (P = 0.022). CONCLUSION: Compared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin were more frequently candidates for local therapy at recurrence.

Local tumour progression after percutaneous ablation of colorectal liver metastases according to RAS mutation status.

BACKGROUND: Percutaneous ablation is a common treatment for colorectal liver metastasis (CLM). However, the effect of rat sarcoma viral oncogene homologue (RAS) mutation on outcome after ablation of CLMs is unclear. METHODS: Patients who underwent image-guided percutaneous ablation of CLMs from 2004 to 2015 and had known RAS mutation status were analysed. Patients were evaluated for local tumour progression as observed on imaging of CLMs treated with ablation. Multivariable Cox regression analysis was performed to determine factors associated with local tumour progression-free survival. RESULTS: The study included 92 patients who underwent ablation of 137 CLMs. Thirty-six patients (39 per cent) had mutant RAS. Rates of local tumour progression were 14 per cent (8 of 56) for patients with wild-type RAS and 39 per cent (14 of 36) for patients with mutant RAS (P = 0·007). The actuarial 3-year local tumour progression-free survival rate after percutaneous ablation was worse in patients with mutant RAS than in those with wild-type RAS (35 versus 71 per cent respectively; P = 0·001). In multivariable analysis, negative predictors of local tumour progression-free survival were a minimum ablation margin of less than 5 mm (hazard ratio (HR) 2·48, 95 per cent c.i. 1·31 to 4·72; P = 0·006) and mutant RAS (HR 3·01, 1·60 to 5·77; P = 0·001). CONCLUSION: Mutant RAS is associated with an earlier and higher rate of local tumour progression in patients undergoing ablation of CLMs.

Unsupervised Learning in PET Radiomics.

In this study, we investigated large scale radoimics on 116 breast cancer patients. We are particularly interested in unsupervised learning to bicluster patients and features in order to associate such biclusters with the disease characteristics. The results show that radiomics features with wavelet features have a better biclustering ability. And 172 radiomics features have shown a better classification capability.

Risk of skin cancer in patients on chronic haemodialysis: a nationwide, population-based study in Taiwan.

BACKGROUND: Patients on chronic haemodialysis (HD) have a higher incidence of cancer. However, the risk of skin cancer in this population has rarely been investigated. OBJECTIVES: To investigate the risk of nonmelanoma skin cancer (NMSC) and cutaneous melanoma in patients on chronic HD and to explore the associated risk factors. METHODS: We performed retrospective cohort and nested case-control studies using records in the Taiwanese National Health Insurance Research Database between 1999 and 2013. The HD cohort included 79 668 incident patients on HD, for whom the standardized incidence ratios (SIRs) for incident NMSC and cutaneous melanoma were determined. In the nested case-control study, patients on HD with NMSC were matched to those without skin cancers. The impact of various factors on the development of NMSC was determined by conditional logistic regression analysis. RESULTS: Among the 79 668 patients on HD, 248 cases of NMSC and 22 cases of cutaneous melanoma occurred after a mean 4·95 years of follow-up. The SIRs for NMSC and cutaneous melanoma in patients on HD were 1·58 (95% confidence interval 1·39-1·79) and 1·44 (95% confidence interval 0·91-2·19), respectively. Of the patients on HD, a higher risk of NMSC was found in men (1·5-fold), South Taiwan residents (twofold) and patients with uraemic pruritus after long-term antihistamine treatment (1·53-fold). However, the incidence of NMSC was not increased in patients with uraemic pruritus receiving ultraviolet B phototherapy. CONCLUSIONS: Patients on chronic HD are at higher risk of NMSC. Uraemic pruritus further increases the risk of NMSC, which might be prevented by ultraviolet B phototherapy.

A rare occurrence of intramasseteric schwannoma - case report and literature review.

A schwannoma is a benign, solitary, well-defined, painless, slowly-enlarging nerve sheath tumor, composed of Schwann cells. Intramasseteric localization is very unusual. We report the case of a 33-year-old male who developed an intramasseteric schwannoma. Tumor could be completely removed under general anesthesia. Histopathological examination made the diagnosis of intramasseteric schwannoma through the presence of Antoni A areas and Verocay bodies. The diagnosis of schwannoma should be taken into consideration in case of parotideomasseteric tumors.

Genetic alterations and their clinical implications in older patients with acute myeloid leukemia.

A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.

Aiolos collaborates with Blimp-1 to regulate the survival of multiple myeloma cells.

The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) has crucial roles in the control of plasma cell differentiation and in maintaining survival of plasma cells. However, how Blimp-1 ensures the survival of plasma cell malignancy, multiple myeloma (MM), has remained elusive. Here we identified Aiolos, an anti-apoptotic transcription factor of MM cells, as a Blimp-1-interacting protein by mass spectrometry. ChIP coupled with DNA microarray was used to profile the global binding of Aiolos and Blimp-1 to endogenous targets in MM cells, which revealed their co-binding to a large number of genes, including apoptosis-related genes. Accordingly, Blimp-1 and Aiolos regulate similar transcriptomes in MM cells. Analysis of the binding motifs for Blimp-1 and Aiolos uncovered a partial motif that was similar across sites for both proteins. Aiolos promotes the binding of Blimp-1 to target genes and thereby enhances Blimp-1-dependent transcriptional repression. Furthermore, treatment with an anti-MM agent, lenalidomide, caused ubiquitination and proteasomal degradation of Blimp-1, leading to the de-repression of a new Blimp-1 direct target, CULLIN 4A (CUL4A), and reduced Aiolos levels. Accordingly, lenalidomide-induced cell death was partially rescued by reintroduction of Blimp-1 or knockdown of CUL4A. Thus, we demonstrated the functional impacts and underlying mechanisms of the interaction between Aiolos and Blimp-1 in maintaining MM cell survival. We also showed that interruption of Blimp-1/Aiolos regulatory pathways contributes to lenalidomide-mediated anti-MM activity.

Effects of fluoride on proliferation and mineralization in periodontal ligament cells in vitro

Fluoride, which is often added to toothpaste or mouthwash in order to protect teeth from decay, may be a novel therapeutic approach for acceleration of periodontal regeneration. Therefore, we investigated the effects of fluoride on proliferation and mineralization in human periodontal ligament cells in vitro. The periodontal ligament cells were stimulated with various concentrations of NaF added into osteogenic inductive medium. Immunohistochemistry of cell identification, cell proliferation, alkaline phosphatase (ALP) activity assay, Alizarin red S staining and quantitative real-time-polymerase chain reaction (RT-PCR) were performed. Moderate concentrations of NaF (50-500 μmol/L) had pro-proliferation effects, while 500 μmol/L had the best effects. ALP activity and calcium content were significantly enhanced by 10 μmol/L NaF with osteogenic inductive medium. Quantitative RT-PCR data varied in genes as a result of different NaF concentrations and treatment periods. We conclude that moderate concentrations of NaF can stimulate proliferation and mineralization in periodontal ligament cells. These in vitro findings may provide a novel therapeutic approach for acceleration of periodontal regeneration by addition of suitable concentrations of NaF into the medication for periodontitis treatment, i.e., into periodontal packs and tissue patches.

TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

Effects of 5-aza-2′deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma

Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2′deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.