Efficacy and safety analysis of continued nursing of complications in discharged patients after percutaneous transhepatic biliary drainage.

BACKGROUND: Percutaneous hepatobiliary drainage (PTCD) is an effective method for the treatment of biliary obstruction and other diseases, but postoperative complications are still one of the important problems faced by patients. Continuous nursing is a comprehensive nursing model that plays an important role in postoperative recovery. The purpose of this study was to investigate the effect of continuous nursing on the incidence of complications in patients after PTCD surgery through meta-analysis and to evaluate its efficacy and safety. AIM: To evaluate the effect of extended nursing on the incidence of complications in discharged patients after percutaneous transhepatic biliary drainage (PTBD). METHODS: Randomized controlled studies on PTBD postdischarge extended care were identified in the CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Embase, Web of Science, and other databases. The quality of the included studies was evaluated using the Joanna Briggs Institute of Australia literature quality evaluation tool, and a meta-analysis of the included studies was performed with RevMan 5.4 software. RESULTS: Finally, 9 studies were included, with a total sample size of 854 patients (425 patients in the control group and 429 patients in the intervention group). Meta-analysis revealed that extended care effectively reduced biliary tract infection (RR: 0.42, 95%CI: 0.30-0.57), puncture wound infection (RR: 0.19, 95%CI: 0.06-0.65), catheter protrusion or displacement in discharged patients after PTBD (RR: 0.31, 95%CI: 0.18-0.54), catheter blockage (RR: 0.23, 95%CI: 0.13-0.42), skin infection around the drainage tube (RR: 0.30, 95%CI: 0.12-0.77), and catheter-related readmissions (RR: 0.34, 95%CI: 0.18-0.65) (P < 0.05). CONCLUSION: Compared with conventional discharge care, extended care can effectively reduce the occurrence of complications such as biliary tract infection, puncture wound infection, catheter prolapse or displacement, catheter blockage, skin infection around the drainage tube, and catheter-related readmission in discharged patients after PTBD.

The ratio of neutrophils to lymphocytes effectively predicts clinical outcomes in idiopathic membranous nephropathy.

BACKGROUND: Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: 112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR. RESULTS: Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009 - 1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237 - 0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693 - 0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001). CONCLUSION: The NLR is an effective indicator for predicting clinical remission in patients with IMN.

Nutlin-3 acts as a DNA methyltransferase inhibitor to sensitize esophageal cancer to chemoradiation.

Esophageal squamous cell carcinoma (ESCC) is highly resistant to chemoradiation therapy. We aimed to examine whether Nutlin-3, a molecule that suppresses murine double min 2 (MDM2)-mediated p53 and Retinoblastoma (RB) protein degradation leading to downregulation of DNA methyltransferases (DNMTs), can be a novel therapeutic agent for ESCC. We used wild-type and chemoradiation-resistant ESCC cell lines in this study. The expression of DNMTs, p53 and RB, and methylation level of tumor suppressor genes (TSG) were analyzed upon Nutlin-3 treatment. The antitumor efficacy of Nutlin-3 was investigated in ESCC cell lines and xenograft tumor model. TSG protein expression was checked in the excised tumor tissue. Nutlin-3 induced upregulation of p53 and RB and downregulation of DNMTs proteins in the chemoradiation-resistant and aggressive ESCC cells. The methylation level of TSGs was decreased by Nutlin-3. Nutlin-3 inhibits clonogenic growth of ESCC cells and exerts a synergistic cytotoxic-effect when combined with chemotherapeutic agent cisplatin. Moreover, xenograft tumor growth in SCID mice was suppressed by Nutlin-3. The protein expression level of DNMTs was downregulated, and that of TSGs was upregulated by Nutlin-3 treatment in the excised tumor tissue. In conclusion, Nutlin-3 is a potential therapeutic agent that can potentiate the treatment efficacy of chemoradiation-resistant ESCC.

Basolateral Amygdala Reactive Microglia May Contribute to Synaptic Impairment and Depressive-Like Behavior in Mice with Bone Cancer Pain.

Anxiety and depression induced by cancer-related pain disturb quality of life and willingness to survive. As a component of the limbic system, the basolateral amygdala (BLA) is critical for processing negative emotions. The reactive microglial engulfment of synapses may promote depression during adolescence. However, whether microglia phagocytose synapses to mediate cancer pain-induced depression remains unclear. The present study established a bone cancer-pain model to investigate the association between dendritic spine synapses and depressive-like behavior and explore the phagocytic function of microglia in the BLA. We found that tumor-bearing mice experienced postoperative pain-related depression, and their BLAs exhibited reactive microglia, as well as phagocytic synapses. The microglial inhibitor minocycline effectively mitigated depressive behavior, synaptic damage, and the phagocytic function of microglia. Our study implicates microglia-mediated synaptic loss in the BLA may act as the pathological basis of depressive-like behavior in bone cancer pain model.

Role of receptor tyrosine kinases mediated signal transduction pathways in tumor growth and angiogenesis-New insight and futuristic vision.

In the past two decades, significant progress has been made in the past two decades towards the understanding of the basic mechanisms underlying cancer growth and angiogenesis. In this context, receptor tyrosine kinases (RTKs) play a pivotal role in cell proliferation, differentiation, growth, motility, invasion, and angiogenesis, all of which contribute to tumor growth and progression. Mutations in RTKs lead to abnormal signal transductions in several pathways such as Ras-Raf, MEK-MAPK, PI3K-AKT and mTOR pathways, affecting a wide range of biological functions including cell proliferation, survival, migration and vascular permeability. Increasing evidence demonstrates that multiple kinases are involved in angiogenesis including RTKs such as vascular endothelial growth factor, platelet derived growth factor, epidermal growth factor, insulin-like growth factor-1, macrophage colony-stimulating factor, nerve growth factor, fibroblast growth factor, Hepatocyte Growth factor, Tie 1 & 2, Tek, Flt-3, Flt-4 and Eph receptors. Overactivation of RTKs and its downstream regulation is implicated in tumor initiation and angiogenesis, representing one of the hallmarks of cancer. This review discusses the role of RTKs, PI3K, and mTOR, their involvement, and their implication in pro-oncogenic cellular processes and angiogenesis with effective approaches and newly approved drugs to inhibit their unrestrained action.

TrkA regulates the regenerative capacity of bone marrow stromal stem cells in nerve grafts.

We previously demonstrated that overexpression of tropomyosin receptor kinase A (TrkA) promotes the survival and Schwann cell-like differentiation of bone marrow stromal stem cells in nerve grafts, thereby enhancing the regeneration and functional recovery of the peripheral nerve. In the present study, we investigated the molecular mechanisms underlying the neuroprotective effects of TrkA in bone marrow stromal stem cells seeded into nerve grafts. Bone marrow stromal stem cells from Sprague-Dawley rats were infected with recombinant lentivirus vector expressing rat TrkA, TrkA-shRNA or the respective control. The cells were then seeded into allogeneic rat acellular nerve allografts for bridging a 1-cm right sciatic nerve defect. Then, 8 weeks after surgery, hematoxylin and eosin staining showed that compared with the control groups, the cells and fibers in the TrkA overexpressing group were more densely and uniformly arranged, whereas they were relatively sparse and arranged in a disordered manner in the TrkA-shRNA group. Western blot assay showed that compared with the control groups, the TrkA overexpressing group had higher expression of the myelin marker, myelin basic protein and the axonal marker neurofilament 200. The TrkA overexpressing group also had higher levels of various signaling molecules, including TrkA, pTrkA (Tyr490), extracellular signal-regulated kinases 1/2 (Erk1/2), pErk1/2 (Thr202/Tyr204), and the anti-apoptotic proteins Bcl-2 and Bcl-xL. In contrast, these proteins were downregulated, while the pro-apoptotic factors Bax and Bad were upregulated, in the TrkA-shRNA group. The levels of the TrkA effectors Akt and pAkt (Ser473) were not different among the groups. These results suggest that TrkA enhances the survival and regenerative capacity of bone marrow stromal stem cells through upregulation of the Erk/Bcl-2 pathway. All procedures were approved by the Animal Ethical and Welfare Committee of Shenzhen University, China in December 2014 (approval No. AEWC-2014-001219).

SOX17 overexpression sensitizes chemoradiation response in esophageal cancer by transcriptional down-regulation of DNA repair and damage response genes.

BACKGROUND: Prognosis of esophageal squamous cell carcinoma (ESCC) patients is poor and the concurrent chemoradiation therapy (CCRT) provided to ESCC patients often failed due to resistance. Therefore, development of biomarkers for predicting CCRT response is immensely important. In this study, we evaluated the predicting value of SRY (sex determining region Y)-box 17 (SOX17) protein during CCRT and its dysregulation of transcriptional targets in CCRT resistance in ESCC. METHODS: Pyrosequencing methylation, RT-qPCR and immunohistochemistry assays were performed to examine the DNA methylation, mRNA expression and protein expression levels of SOX17 in endoscopic biopsy from a total of 70 ESCC patients received CCRT. Cell proliferation, clonogenic survival and xenograft growth were used to confirm the sensitization of ESCC cell line KYSE510 in response to cisplatin, radiation or CCRT treatment by SOX17 overexpression in vitro and in vivo. Luciferase activity, RT-qPCR and ChIP-qPCR assays were conducted to examine transcription regulation of SOX17 in KYSE510 parental, KYSE510 radio-resistant cells and their derived xenografts. RESULTS: High DNA methylation coincided with low mRNA and protein expression levels of SOX17 in pre-treatment endoscopic biopsy from ESCC patients with poor CCRT response. SOX17 protein expression exhibited a good prediction performance in discriminating poor CCRT responders from good responder. Overexpression of SOX17 sensitized KYSE510 radio-resistant cells to cisplatin, radiation or CCRT treatment in cell and xenograft models. Importantly, SOX17 transcriptionally down-regulated DNA repair and damage response-related genes including BRCA1, BRCA2, RAD51, KU80 DNAPK, p21, SIRT1, NFAT5 and REV3L in KYSE510 radio-resistant cells to achieve the sensitization effect to anti-cancer treatment. Low expression of BRCA1, DNAPK, p21, RAD51 and SIRT1 was confirmed in SOX17 sensitized xenograft tissues derived from radio-resistant ESCC cells. CONCLUSIONS: Our study reveals a novel mechanism by which SOX17 transcriptionally inactivates DNA repair and damage response-related genes to sensitize ESCC cell or xenograft to CCRT treatment. In addition, we establish a proof-of-concept CCRT prediction biomarker using SOX17 immunohistochemical staining in pre-treatment endoscopic biopsies to identify ESCC patients who are at high risk of CCRT failure and need intensive care.

Role of BCL2L10 in regulating buffalo (Bubalus bubalis) oocyte maturation.

It has been reported that BCL2L10 is abundantly and specifically expressed in adult human and mouse oocytes and played a very important role in oocytes maturation and early embryonic development. This study is to investigate the expression pattern of BCL2L10 in buffalo ovaries and its effect on the in vitro maturation of buffalo oocytes, so as to dissect mechanism of oocytes maturation and provide theoretical guidance for improvement of the in vitro maturation of buffalo oocytes. The results showed that BCL2L10 gene was enriched in ovary and the expression of BCL2L10 was oocyte specific and up-regulated during oocyte maturation. BCL2L10 protein and mRNA were detectable in buffalo early embryos, upregulated at 2-cell to 8-cell stages and down-regulated in the later stages. Knockdown of BCL2L10 by RNA interference resulted in a significant decrease in the maturation rate (33.5%) and cleavage rate (37.52%) of buffalo oocytes coupled with up-regulation of apoptosis-related gene Caspase-9. We concluded that BCL2L10 is a candidate associated with buffalo oocyte maturation.

Oxypurinol-Specific T Cells Possess Preferential TCR Clonotypes and Express Granulysin in Allopurinol-Induced Severe Cutaneous Adverse Reactions.

Allopurinol, a first-line drug for treating gout and hyperuricemia, is one of the leading causes of severe cutaneous adverse reactions (SCARs). To investigate the molecular mechanism of allopurinol-induced SCAR, we enrolled 21 patients (13 Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and 8 drug reaction with eosinophilia and systemic symptoms (DRESS)), 11 tolerant controls, and 23 healthy donors. We performed in vitro T-cell activation assays by culturing peripheral blood mononuclear cells (PBMCs) with allopurinol, oxypurinol, or febuxostat and measuring the expression of granulysin and IFN-γ in the supernatants of cultures. TCR repertoire was investigated by next-generation sequencing. Oxypurinol stimulation resulted in a significant increase in granulysin in the cultures of blood samples from SCAR patients (n=14) but not tolerant controls (n=11) or healthy donors (n=23). Oxypurinol induced T-cell response in a concentration- and time-dependent manner, whereas allopurinol or febuxostat did not. T cells from patients with allopurinol-SCAR showed no crossreactivity with febuxostat. Preferential TCR-V-ß usage and clonal expansion of specific CDR3 (third complementarity-determining region) were found in the blister cells from skin lesions (n=8) and oxypurinol-activated T-cell cultures (n=4) from patients with allopurinol-SCAR. These data suggest that, in addition to HLA-B*58:01, clonotype-specific T cells expressing granulysin upon oxypurinol induction participate in the pathogenesis of allopurinol-induced SCAR.

Low SOX17 expression is a prognostic factor and drives transcriptional dysregulation and esophageal cancer progression.

The transcriptional network of the SRY (sex determining region Y)-box 17 (SOX17) and the prognostic impact of SOX17 protein expression in human cancers remain largely unclear. In this study, we evaluated the prognostic effect of low SOX17 protein expression and its dysregulation of transcriptional network in esophageal squamous cell carcinoma (ESCC). Low SOX17 protein expression was found in 47.4% (73 of 154) of ESCC patients with predicted poor prognosis. Re-expression of SOX17 in ESCC cells caused reduced foci formation, cell motility, decreased ESCC xenograft growth and metastasis in animals. Knockdown of SOX17 increased foci formation in ESCC and normal esophageal cells. Notably, 489 significantly differential genes involved in cell growth and motility controls were identified by expression array upon SOX17 overexpression and 47 genes contained putative SRY element in their promoters. Using quantitative chromatin immunoprecipitation-PCR and promoter activity assays, we confirmed that MACC1, MALAT1, NBN, NFAT5, CSNK1A1, FN1 and SERBP1 genes were suppressed by SOX17 via the SRY binding-mediated transcriptional regulation. Overexpression of FN1 and MACC1 abolished SOX17-mediated migration and invasion suppression. The inverse correlation between SOX17 and FN1 protein expression in ESCC clinical samples further strengthened our conclusion that FN1 is a transcriptional repression target gene of SOX17. This study provides compelling clinical evidence that low SOX17 protein expression is a prognostic biomarker and novel cell and animal data of SOX17-mediated suppression of ESCC metastasis. We establish the first transcriptional network and identify new suppressive downstream genes of SOX17 which can be potential therapeutic targets for ESCC.

Discovery and evaluation of 3-phenyl-1H-5-pyrazolylamine-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3).

Preclinical investigations and early clinical trial studies suggest that FLT3 inhibitors offer a viable therapy for acute myeloid leukemia. However, early clinical data for direct FLT3 inhibitors provided only modest results because of the failure to fully inhibit FLT3. We have designed and synthesized a novel class of 3-phenyl-1H-5-pyrazolylamine-derived compounds as FLT3 inhibitors which exhibit potent FLT3 inhibition and high selectivity toward different receptor tyrosine kinases. The structure-activity relationships led to the discovery of two series of FLT3 inhibitors, and some potent compounds within these two series exhibited comparable potency to FLT3 inhibitors sorafenib (3) and ABT-869 (4) in both wt-FLT3 enzyme inhibition and FLT3-ITD inhibition on cell growth (MOLM-13 and MV4;11 cells). In particular, the selected compound 12a exhibited the ability to regress tumors in mouse xenograft models using MOLM-13 and MV4;11 cells.

Digital mucous cysts presenting as numerous translucent nodules in the right fifth finger.

Digital mucous cysts is a common benign skin disease usually present as solitary or a few soft, translucent to slightly bluish nodules. Here, we report the case of a 90-year-old male patient with numerous translucent nodules on his right fifth finger. Although he had one of them drained, they recurred afterward. Skin biopsy was done on the ventral side of the fifth distal phalange, and clear viscous fluid was noted during the procedure. The surrounding bulging nodules became flattened after milking. By hematoxylin and eosin stain, the section showed a cystic lesion in the dermis. The cyst wall was devoid of a true lining, consisting of eosinophlic, compact, slightly hyalinized collagen. In the cystic space, there was only a small amount of mucin. He was therefore diagnosed with multiple digital mucous cysts. We treated him with intralesional steroid injection and compressive dressing. Two weeks later, however, the skin lesions recurred despite the treatments.

Cancer risks of dermatomyositis and polymyositis: a nationwide cohort study in Taiwan.

INTRODUCTION: The association of idiopathic inflammatory myositis (IIM) and malignancies has been reported, but rarely in Asian countries. Our aim was to investigate the risk of cancer among IIM patients without a prior history of malignancies, in Taiwan. METHODS: We conducted a nationwide cohort study of 1,012 patients with dermatomyositis (DM) and 643 patients with polymyositis (PM), but without prior history of malignancies, utilizing the National Health Insurance Database from 1997 to 2007. Standardized incidence ratios (SIRs) of cancers were analyzed. RESULTS: A total of 95 cancers (9.4%) in DM and 33 cancers (4.4%) in PM were identified. Overall cancer risk was significantly elevated in DM patients (SIR = 5.11, 95% confidence interval [CI] = 5.01 to 5.22) and PM patients (SIR = 2.15, 95% CI = 2.08 to 2.22). Most cancers were detected in the first year of observation. The risk of cancer decreased with observation time, yet remained elevated compared with the general population in both study groups after 5 years of follow-up. DM was associated with sustained elevated risk of cancers in every age group, whereas the risk of cancer in PM was highest in younger patients and decreased with age. DM patients were at the greatest risk of cancers of the nasopharynx, lungs and hematopoietic malignancies. CONCLUSIONS: Patients with IIM are at increased risk for cancer and should receive age-appropriate and gender-appropriate malignancy evaluations, with additional assessment for nasopharyngeal, lung and hematologic malignancy following diagnosis, and with continued vigilance for development of cancers in follow-up.

Epidemiological features and costs of herpes zoster in Taiwan: a national study 2000 to 2006.

To analyse the epidemiological characteristics and related costs of herpes zoster in Taiwan, a nationally representative cohort of 1,000,000 individuals from the National Health Insurance register was followed up from 2000 to 2006 and their claims data analysed. Overall, 34,280 patients were diagnosed with zoster (incidence 4.89/1000 person-years) and 2944 patients (8.6%) developed post-herpetic neuralgia 3 months after the start of the zoster rash (incidence 0.42/1000 person-years). People with older age, diabetes, and immunocompromising conditions were at higher risk of developing zoster and post-herpetic neuralgia. The overall hospitalization rate for zoster was 16.1 cases per 100,000 person-years. The cost for each home care case and per hospitalized case were approximately 53.30 euro and 1224.70 euro, respectively. Further research into the cost-effectiveness of zoster vaccine is needed.

Epidemiological study of psoriasis in the national health insurance database in Taiwan.

The aim of this study was to determine the prevalence, treatment modalities and comorbidity of psoriasis in Taiwan. A nationally representative cohort of 1,000,000 individuals from the National Health Insurance database was followed up for the years 2000 to 2006. Their claims data was used for an epidemiological study. The mean one-year prevalence of psoriasis was 0.23% for men and 0.16% for women, respectively. The prevalence of psoriasis increased more rapidly in male patients aged 30 years and over and reached its peak in patients aged 70 years and over, regardless of sex. Overall, 98.4% of patients received treatment with topical corticosteroids, while 13.1% used Chinese herbal medicines and 13.6% received systemic treatment. Patients with psoriasis had a higher comorbidity of diabetes, hyperlipidaemia, and hypertension. In conclusion, in contrast to Caucasians, the prevalence of psoriasis in Taiwanese people is high er in men than in women and the prevalence increases significantly in patients over 70 years of age.

[Detection of chromosomal aberrations in nasopharyngeal carcinoma by rapid primed in situ labeling].

BACKGROUND & OBJECTIVE: The chromosomal aberration is common in nasopharyngeal carcinoma (NPC). The currently-used methods for detecting chromosomal abnormalities are complicated and of limited clinical value. The purpose of the present study was to explore the feasibility of detecting chromosomal abnormalities in NPC by rapid primed in situ labeling (RPRINS). METHODS: Using RPRINS technique with specific oligonucleotide primers of chromosome 3 and 7, the abnormalities of chromosome 3 and 7 in the frozen section tissues of 15 cases of NPC and 5 cases of normal nasopharyngeal mucosa (NNM) were detected. Loss of chromosome was defined when the percentage of cells with labeling signals /=65%, and the increase in chromosomal copy number was defined when the percentage of cells with labeling signals >/=3 was >/=6.5%. RESULTS: In 15 cases of NPC tissues, the chromosome 3 had a labeling rate of 88.6% and increasing copy numbers in ten cases (66.7%), and the chromosome 7 had a labeling rate of 87.4% and loss of chromosome in five cases (33.3%). Four cases coexisted with increasing chromosome 3 copy numbers and loss of chromosome 7. In contrast, the labeling rates of chromosome 3 and 7 in NNM were 92.0% and 91.8%, respectively, and the percentage of diploid cells were 43.2% and 43.6%, respectively, with absence of triploid. There was a significant difference in the percentage of diploid cells between NPC and NNM (P< 0.05). CONCLUSION: The technique of rapid PRINS could be used to detect chromosomes in frozen section tissues, and the chromosomal abnormalities would be helpful in diagnosis of NPC.