The Clinical Characteristics and Antihypertensive Medications for Mortality of Elderly Hospitalized Hemodialysis patients: a Multicenter Retrospective Study in China.

This study aimed to evaluate the clinical characteristics and antihypertensive medications affecting elderly hemodialysis (HD) patient mortality. This retrospective cohort study enrolled patients (≥18 years old) discharged from 15 tertiary general hospitals in China between January 1, 2009, and December 31, 2011. The characteristics of elderly HD patients (≥60 years old) and antihypertensive medications for mortality were analyzed. A total of 7135 patients on maintenance HD, including 2738 elderly patients, were enrolled in this study. The mean levels of hemoglobin, albumin, serum calcium, phosphorus, and parathyroid hormone in elderly group were lower than the younger group (P <0.05). The top two reasons for the hospitalization of elderly patients were infection and cardiovascular disease (CVD). We compared the characteristics of 2492 survived elderly maintenance HD patients and 246 patients who died. Aging [odds ratio OR = 1.59, 95% confidence interval (CI): 1.13-2.24] and central venous catheter (CVC) (OR = 1.62, 95% CI: 1.53-1.72) were independently risk factors for mortality in elderly maintenance HD patients. Maintenance HD patients with high levels of hemoglobin (OR = 0.76, 95% CI: 0.73-0.79), albumin (OR = 0.87, 95% CI: 0.77-0.98), uric acid (OR = 0.90, 95% CI: 0.84-0.9) and those taking angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker (OR = 0.77, 95% CI: 0.58-0.90) had a lower risk of mortality. Other antihypertensive drugs including: ß-blockers, calcium channel blockers, and α-blockers were not significantly associated with mortality (P >0.05). CVD and infection were the most common causes of hospitalization and/or mortality in elderly HD patients. Age, anemia and malnutrition, use of CVCs, and low level of serum uric acid are the risk factors for mortality in elderly maintenance HD patients. Renin-angiotensin system blockade might provide a benefit in protecting elderly maintenance HD patients from mortality.

linc01088 promotes cell proliferation by scaffolding EZH2 and repressing p21 in human non-small cell lung cancer.

AIMS: Non-small cell lung cancer (NSCLC), characterized by extensive metastasis and poor prognosis, is the most common type of lung cancer. Dysregulation of certain lncRNAs is known to be linked to the tumorigenesis of NSCLC. However, the specific roles in NSCLC for many other lncRNAs, such as linc01088, remain largely unknown. MATERIALS AND METHODS: The expression patterns of linc01088, p21 and EZH2 were examined both in NSCLC tissues and cell lines using RT-qPCR assay. CCK-8, colony formation, immunofluorescence staining, and flow cytometry assays were employed to evaluate the effects of linc01088 on NSCLC cell proliferation properties. RNA immunoprecipitation (RIP) assay was performed to determine the direct binding relationship between linc01088 and zeste homolog 2 (EZH2). Western blot and RT-qPCR analysis were performed to assess p21 level within knockdown of either linc01088 or EZH2. Nude mouse subcutaneous NSCLC models were constructed for further validating the effects and mechanisms of linc01088 in vivo. KEY FINDINGS: linc01088 and EZH2 were highly expressed both in NSCLC tissues and cell lines. Knockdown of linc01088 suppressed the proliferation of NSCLC cells, and prolonged the G1 phase while shortened S and G2-M phases. RIP assay revealed the direct binding relationship between linc01088 and EZH2. Knockdown of either linc01088 or EZH2 induced up-regulation of p21 expression, which subsequently inhibited the tumor growth. SIGNIFICANCE: We demonstrated that linc01088 could promote cell proliferation via binding with EZH2 to repress p21, which aggravates the tumorigenesis of NSCLC. Therefore, linc01088 might be a potential oncogene and target for novel anti-tumor therapies.

Association of the malnutrition-inflammation score with anthropometry and body composition measurements in patients with chronic kidney disease.

BACKGROUND: The malnutrition-inflammation score (MIS) is a nutritional scoring system that has been validated in chronic kidney disease (CKD) stages III-V, especially in dialysis patients. We aimed to test whether the MIS changed in the early stages of CKD and whether it was associated with anthropometry and body composition measurements (BCMs) in patients with CKD. METHODS: This was a cross-sectional study conducted in the Nephrology Department. A total of 144 patients with CKD were included in the study between May 2017 and December 2017. The MIS was calculated without computing the dialysis vintage in the scoring. Body composition was measured using a portable whole-body bioimpedance spectroscopy device. Anthropometric, laboratory, and other body composition parameters were recorded. RESULTS: The MIS was increased in patients with CKD. It was negatively correlated with body mass index (BMI), mid-arm muscle circumference (MAMC), handgrip strength, lean tissue index (LTI), fat tissue index (FTI), phase angle (PA), and hemoglobin and albumin concentrations, and it was positively correlated with sex, overhydration, urinary protein excretion and IL-6. A high MIS was significantly correlated with a low LTI (r=-0.274; P=0.001), low FTI (r=-0.179; P=0.032), overhydration (r=0.457; P<0.001) and low PA (r=-0.475; P<0.001). A rather strong correlation was observed between the PA and the MIS. In the multivariate regressions, after adjusting for age, sex, presence of diabetes, handgrip strength, BMI, overhydration, glomerular filtration rate, albumin and IL-6 concentrations, these relationships did not diminish. CONCLUSIONS: The MIS was strongly linked with indicators of nutrition. As a simple and practical tool for assessing nutritional status, the MIS should be calculated in the early stages of CKD.

Methionine restriction delays senescence and suppresses the senescence-associated secretory phenotype in the kidney through endogenous hydrogen sulfide.

Aging is a risk factor for various acute and chronic kidney injuries. Kidney aging is accompanied by the secretion of growth factors, proteases, and inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). These factors accelerate the aging process and senescence-associated changes. Delaying kidney senescence may prevent acute and chronic kidney injury. Methionine restriction (MR) was found to be an effective intervention for delaying senescence. However, the mechanism of MR remains unclear. In this study, we investigated the effect of MR on the survival rate and renal aging of C57BL/6 mice and examined the relevant mechanisms. MR increased the survival rate and decreased the levels of senescence markers in the aging kidney. Both in vivo and in vitro, MR upregulated the transsulfuration pathway to increase H2S production, downregulated senescence markers and the SASP, and activated AMPK. The ability of MR to delay aging was reduced when AMPK was inhibited. These results suggest that MR may slow animal aging and kidney senescence through H2S production and AMPK pathway activation. Abbreviations: DR: diet restriction; MR: methionine restriction; SASP: senescence-associated secretory phenotype; AL: ad libitum; CKD, chronic kidney disease; AKI: acute kidney disease; TSP: transsulfuration pathway; CGL: cystathionine g-lyase; H2S: hydrogen sulfide; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; IS: indoxyl sulfate; CC: compound C.

The prevalence of depression and the association between depression and kidney function and health-related quality of life in elderly patients with chronic kidney disease: a multicenter cross-sectional study.

Purpose: The prevalence of depression and the relationship between depression and kidney function and health-related quality of life (HRQOL) are not well understood in elderly patients with predialysis chronic kidney disease (CKD). This study aimed to evaluate the prevalence of depression and the association between depression and kidney function and HRQOL. Patients and methods: In this cross-sectional study, 1079 elderly participants with CKD were recruited at 32 clinical centers located within 26 cities throughout 24 provinces in China. Demographic information and laboratory analyses were collected. Symptoms of depression were assessed using the 15-item Geriatric Depression Scale (GDS-15). HRQOL was evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36) instrument. Results: The prevalence of depression was 23.0%. The estimated glomerular filtration rate (eGFR) was negatively correlated with the GDS score whether it was treated as a categorical variable (r=-0.097, P=0.001) or as a continuous variable (r=-0.100, P=0.001). Marital status, education level, history of CVD and diabetes, CKD stage and proteinuria confirmed to be independent and significant predictors of depression in patients with CKD. Compared with CKD 1-2 patients, we observed an increase of 0.541 and 4.171 in the odds for developing depression in patients CKD 4 (odds ratio [OR] =1.541; P=0.031) and CKD 5 (odds ratio [OR] =5.171; P<0.001), respectively. We observed negative and significant correlations with the GDS score for the following components: PCS (r=-0.370, P<0.001), MCS (r=-0.412, P<0.001), burden of kidney disease (r=-0.403, P<0.001), symptoms and problems of kidney disease (r=-0.360, P<0.001) and effects of kidney disease (r=-0.355, P<0.001). Depression was an independent and significant predictor of all the subcomponents of the HRQOL. Conclusions: The prevalence of depression in elderly patients with CKD was high and was negatively correlated with kidney function. Depression had a major negative impact on HRQOL.

Exercise intervention alleviates nerve injury by the suppression of inflammatory mediator expression via the TLR4/NF-κB signaling pathway.

Spinal cord injury (SCI) may cause changes that have damaging effects on sensation and functionality. However, methods for the significant amelioration of SCI-reduced nerve injury are lacking. Previous studies have indicated that reasonable and effective exercise may promote the recovery of injured nerves. Therefore, the aim of the present study was to investigate the ability of exercise to improve recovery following SCI and the underlying mechanism. A rat model was used to evaluate the effects of two different periods of exercise intervention on recovery following SCI. The exercise intervention comprised 15 or 30 min/day passive walking for 30 days. ELISA measurements were used to analysis the plasma levels of inflammatory cytokines. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to examine the levels of proteins and mRNAs associated with nuclear factor (NF)-κB-related signaling. In addition, histological examination and immunostaining were used to evaluate the neural injury and associated indicators. The results indicated that severe SCI induced a peripheral inflammatory response and increased the expression of inflammatory cytokines. In addition, the SCI-induced nerve injury was associated with increased glial fibrillary acidic protein (GFAP) expression and the upregulation of Toll-like receptor 4 (TLR4)/NF-κB signaling, which may further aggravate the inflammatory responses induced by SCI. However, the exercise intervention decreased SCI-induced GFAP expression and reduced the activation of the TLR4/NF-κB signaling pathway compared with that of SCI model rats that did not exercise. Furthermore, the exercise intervention inhibited the release of inflammatory cytokines into the serum. These results indicate that exercise treatment reduces inflammation and glial activation, and may be beneficial to recovery following SCI.

Impact of aging on the risk of platinum-related renal toxicity: A systematic review and meta-analysis.

BACKGROUND: Renal toxicity limits the clinical use of platinum-based therapy in the elderly. In order to clarify the impact of aging on the risk of platinum-related nephrotoxicity, the following meta-analysis was performed. METHODS: We searched multiple databases for studies published before January 2017. The inclusion criteria were case-control, cohort studies published in any language. RESULTS: The risk of platinum-induced nephrotoxicity in the older group was 1.43 times (risk rate) higher than in the non-older group. Platinum-induced nephrotoxicity in older patients was mainly I/II. There was no significant difference in the incidence of grade III/IV renal toxicity between groups. The risk for elderly patients in Asia was significantly higher than in Europe and North America. Carboplatin had a lower risk of renal toxicity and only half of the amount of moderate and severe nephrotoxicity than cisplatin. In the age stratification analysis, the RR values were 1.43, 1.51 and 1.35 respectively for the elderly group (55, 60, 70 years old), and all had significant differences. The risk of platinum-related nephrotoxicity in elderly patients was significantly increased in the high comorbidity rate group. Moreover, the RR values of the normal renal function group were significantly higher than that of the 'no mention or renal insufficiency' subgroup. CONCLUSIONS: Aging increased the risk of platinum-induced nephrotoxicity by 43%, partly due to more comorbidities in elderly patients, and mild renal toxicity was dominant. The risk of renal toxicity of the elderly patients in Asian countries was much higher than that of in European countries and North America.

The characteristics and risk factors for cisplatin-induced acute kidney injury in the elderly.

OBJECTIVES: The most serious adverse reaction of cisplatin is acute kidney injury (AKI). Cisplatin-induced acute kidney injury (CIA) has no specific preventive measures. This study aims to explore the characteristics and risk factors for CIA in the elderly and to identify potential methods to reduce CIA. MATERIALS AND METHODS: Patients ≥18 years old, with primary tumors, who received initial cisplatin chemotherapy and whose serum creatinine (SCr) values were measured within 2 weeks pre- and postcisplatin treatment and who had complete medical records, were selected from a single center from January 1, 2013 to December 31, 2015. The exclusion criteria included radiotherapy or surgery, recurrent tumors, previous cisplatin treatment, lack of any SCr values before or after cisplatin therapy, and incomplete medical records. RESULTS: Out of a total of 527 patients, 349 were elderly. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use (9.2%) was more prevalent in the elderly than in younger patients (2.8%, p = 0.007). The dosage of cisplatin treatment was lower in the elderly, but the incidence of CIA (9.46%) was higher in the elderly than in younger patients (3.37%). There were significant differences in the SCr levels, estimated glomerular filtration rate, ACEI/ARB use, and whether a single application of cisplatin was administered, between the elderly AKI group and the non-AKI group. Multivariable analysis showed that administration of a single application of cisplatin (OR 2.853, 95% CI: 1.229, 6.621, p = 0.015) and ACEI/ARB use (OR 3.398, 95% CI: 1.352, 8.545, p = 0.009) were predictive factors for developing CIA in the elderly. CONCLUSION: The incidence of CIA in the elderly was higher than in younger patients. ACEI/ ARB usage and administration of a single application of cisplatin were independent risk factors for CIA in the elderly.

Characteristics of and risk factors for death in elderly patients with acute kidney injury: a multicentre retrospective study in China.

PURPOSE OF THE STUDY: The incidence of acute kidney injury (AKI) with a poor prognosis in the elderly has been increasing each year. This study aimed to investigate the clinical characteristics of and risk factors for death from AKI in the elderly and help improve prognosis. STUDY DESIGN: This study was a retrospective cohort study based on data from adult patients (≥18 years old) admitted to 15 hospitals in China between 1 January 2009 and 31 December 2011. The characteristics of AKI in the elderly were compared with those in younger patients. RESULTS: In elderly patients with AKI, rates of hypertension, cardiovascular disease and multiple organ dysfunction syndrome (MODS) were higher than in younger patients (44.2% vs 31.2%, 16.1% vs 4.6% and 20.9% vs 16.9%, respectively), the length of ICU stay was longer (3.8 days vs 2.7 days, P=0.019) and renal biopsy (1.0% vs 7.13%, P<0.001) and dialysis (9.6% vs 19.2%, P<0.001) were performed less. Hospital-acquired (HA) AKI was more common than community-acquired (CA) AKI (60.3% vs 39.7%), while the most common cause of AKI was pre-renal (53.5%). Multiple logistic regression analysis showed that age (OR 1.041, 95% CI 1.023 to 1.059), cardiovascular disease (OR 1.980, 95% CI 1.402 to 2.797), cancer (OR 2.302, 95% CI 1.654 to 3.203), MODS (OR 3.023, 95% CI 1.627 to 5.620) and mechanical ventilation (OR 2.408, 95% CI 1.187 to 4.887) were significant risk factors for death. CONCLUSIONS: HA-AKI and pre-renal AKI were more common in the elderly. Age, cardiovascular disease, cancer, MODS and mechanical ventilation were independent risk factors for death in the elderly with AKI.

miR-200b regulates epithelial-mesenchymal transition of chemo-resistant breast cancer cells by targeting FN1.

Chemotherapy is a cornerstone treatment for early and advanced stage breast cancer patients. However, resistance to chemotherapy remains a major obstacle, resulting in disease relapse and progression. Emerging studies demonstrated that miRNAs regulate chemotherapy-induced epithelial-mesenchymal transition (EMT) and drug resistance, but the underlying mechanisms remain unclear. Here we established a doxorubicin-resistant breast cancer cell line MCF-7/Adr, and found these cells exhibited an EMT phenotype featured by a fibroblast-like morphology, increased the capacity of migration and invasion, and underwent the changes of molecular markers of EMT including E-cadherin, N-cadherin, and vimentin. We then compared the miRNA expression profiles between MCF-7/Adr and parental MCF-7 by miRNA microarray, and identified miR-200b as the most dramatically down-regulated miRNA. Overexpression of miR-200b in chemo-resistant cells reversed the EMT phenotype and increased sensitivity to doxorubicin. Inhibition of miR-200b in parental cells induced EMT and resistance to doxorubicin. Furthermore, we characterized the target gene of miR-200b, and showed that overexpression of miR-200b down-regulated FN1 expression and the luciferase activity. Compared with the parental cells, FN1 was significantly elevated in MCF-7/Adr cells. Knockdown of FN1 reversed mesenchymal morphology, inhibited cell migration and invasion, and sensitized cells to doxorubicin. Our data suggest that miR-200b regulates EMT of chemo-resistant breast cancer cells by targeting FN1. miR-200b-based therapy may be an effective strategy in treating advanced breast cancer patients.

The effectiveness and safety of dual antiplatelet therapy in ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis in Chinese patients: A randomized and controlled trail.

BACKGROUND: There are limited data on the effect of dual antiplatelet treatment with clopidogrel plus aspirin in patients with ischemic cerebrovascular disease and intracranial and extracranial arteriostenosis. The aim of our study was to evaluate the efficacy and safety of aspirin plus clopidogrel in the treatment of ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis. METHODS: Patients with clinically evident acute cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis (greater than 50%) who were unsuitable or reluctance to perform stent implantation were enrolled in this study. We randomly assigned these patients to receive clopidogrel (75 or 50 mg) plus aspirin (100 mg) or aspirin (100 mg) once daily through 90 days, and followed them for 90 days. We examined the main endpoints including the recurrence of stroke, death from cardiovascular causes, and bleeding events. RESULTS: In all, 200 patients were recruited and followed for 90 days. Ischemic stroke occurred in 6 patients (9.1%) treated with 50 mg clopidogrel and aspirin, 6 patients (9.1%) receiving 75 mg clopidogrel and aspirin, whereas 19 patients (27.9%) in the aspirin group (aspirin alone vs copidogrel 50 mg plus aspirin; 95% confidence intervals 1.704-23.779, P < 0.05; aspirin alone vs copidogrel 75 mg plus aspirin; 95% confidence intervals 1.190-13.240, P < 0.05). There were more hemorrhagic events among recipients (3 patients [2.3%]) in the copidogrel plus aspirin group than aspirin recipients (0 patient [0%]), including 1 subcutaneous hemorrhage in the group of 50 mg clopidogrel and aspirin, doubling the number of nasal and gum bleeding in the group of 75 mg clopidogrel and aspirin (P > 0.05). No intracranial hemorrhage and gastro-intestinal hemorrhage occurred in these 3 groups. CONCLUSION: Accordingly, 50 mg clopidogrel plus aspirin, and 75 mg clopidogrel plus aspirin were all superior to aspirin alone as stroke prevention in patients with cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis. The effect of secondary stroke prevention was similar between 50 mg clopidogrel plus aspirin and 75 mg clopidogrel plus aspirin. The therapy of 75 mg clopidogrel plus aspirin resulted in a worrisome tread in bleeding events.

[Herpes simplex virus-mediated RNA interference targeting vesicular glutamate transporter 3 attenuates tactile allodynia in mice].

OBJECTIVE: To construct a replication-deficient herpes simplex virus (HSV-1) for delivering a short hairpin RNA (shRNA) targeting vesicular glutamate transporter 3 (VGLUT3) and observe its effect in alleviating allodynia in mice. METHODS: The recombinant HSV-1 vector carrying the shRNA targeting Vglut3 (HSV-1-shvglut3) was constructed and inoculated in the sciatic nerve in a mouse model of mechanical allodynia to test its analgesia effect. Mechanical allodynia and heat hypersensitivity of the mice were tested by von Frey filaments and Hargreaves' test, respectively. VGLUT3 expression in the dorsal root ganglion (DRG) was evaluated by immunohistochemistry and Western blotting. RESULTS: Following inoculation in the sciatic nerve, the HSV vector HSV-1-shvglut3 was retrogradely transported to the DRG. Mechanical withdraw thresholds of the mouse models receiving HSV-1-shvglut3 inoculation were reversed to nearly the baseline level, and VGLUT3 expression in the DRG was down-regulated 2 weeks after vector inoculation. The analgesic effect lasted for over 2 weeks in these mice without obvious systematic side effects or changes in heat hypersensitivity threshold. CONCLUSION: Vglut3 in the DRG is a promising therapeutic target for alleviating mechanical allodynia, and HSV-1 vector-mediated RNA interference is safe and efficient for inducing long-lasting analgesia after peripheral inoculation of the vector.

Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of SIGIRR to Inhibit NF-κB Signaling Pathway.

BACKGROUND: Chronic inflammation is thought to be a determinant of the aging rate and longevity. Caloric restriction (CR) attenuates age-related increases in the systemic levels of several pro-inflammatory mediators, but the anti-inflammatory mechanisms of CR in the aging process remain unclear. METHODS: Fisher 344 rats in a CR group were fed an amount of food corresponding to 60% of that fed to an ad libitum-fed (AL) group for 8 months. Biochemical analyses and renal pathological grading were used to analyze physiological status. Important signaling molecules in the Toll-like receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR/NF-κB) pathway were also analyzed by western blotting, immunofluorescence and immunohistochemistry. RESULTS: 1) Compared with AL feeding, CR decreased aging-mediated increases in both biochemical marker levels and renal pathological grading. 2) Single immunoglobulin IL-1 (IL-1)-related receptor (SIGIRR) expression decreased with increasing age, but CR led to overexpression. 3) The expression of TLR4 was significantly higher in the CR group than in the AL group. 4) SIGIRR overexpression decreased the expression of the adaptor molecules myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase 4 (IRAK4) and tumor necrosis factor receptor-associated factor 6 (TRAF6). 5) The levels of the inflammatory markers phospho-IκBα and phospho-NF-κB p65 decreased in the CR group. CONCLUSIONS: The inflammatory response might be alleviated by SIGIRR via blockade of the TLR4/NF-κB signaling pathway. Therefore, CR can decrease inflammation via SIGIRR overexpression, and SIGIRR might be a new target to delay aging.

Vitrification of in vitro matured oocytes: effects on meiotic spindle configuration and mitochondrial function.

BACKGROUND: In the assisted reproductive technique, cryopreserving in vitro-matured oocytes is a new strategy to extend the pool of total oocytes. However, oocyte cryopreservation technique is still unsatisfied. So the assessment of cyro-damage on meiotic spindle and mitochondrial function is necessary to evaluate and refine the current protocols. MATERIAL AND METHODS: The immature oocytes were donated from women undergoing ICSI cycles. Cytoskeleton was assessed by α-tubulin and mitochondria through the fluorescent ΔΨm reporter JC-1. RESULTS: Relative inner membrane potential in MII oocytes from vIVM group sharply decreased, compared with the control (n=30) (1.397 vs. 1.019, P<0.05). 45.2% defective spindles were observed in fIVM group, compared with 48.0% in vIVM group (P>0.05). Oocytes in fIVM (35.5%, 11/31) and vIVM (40.0%, 10/25) displayed abnormal chromosome (P>0.05). CONCLUSION: In vitro maturation (IVM) has an adverse effect on the organization of spindle and chromosome, and no significantly effect on spindle and chromosome was discovered after vitrification-thaw cycle, while there was obvious damage of oocyte mitochondrial function of in vitro-matured oocyte detected after warming, which may be the reason of the low following developmental potential.

Overexpression of MTA1 and loss of KAI-1 and KiSS-1 expressions are associated with invasion, metastasis, and poor-prognosis of gallbladder adenocarcinoma.

AIMS AND BACKGROUND: Over 90% of patients with gallbladder cancer have invasion and/or metastasis when they are diagnosed at the clinic. Such patients usually have an extremely poor prognosis. The molecular mechanism responsible for the high prevalence of invasion and metastasis remains unknown. METHODS: We investigated the expression of two metastasis-suppression genes--KAI-1 and KiSS-1--and a metastasis-associated gene--MTA1--in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using in situ hybridization or immunohistochemistry. RESULTS: We demonstrated that positive MTA1 expression was significantly higher whereas positive expressions of KAI-1 and KiSS-1 genes were significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, polyps, and chronic cholecystitis. Positive MTA1 expression was significantly lower, but positive KAI-1 and KiSS-1 expressions were significantly higher in cases with well-differentiated adenocarcinoma, smaller tumor mass, no metastasis of lymph node, and no invasion of regional tissues than in cases having poorly differentiated adenocarcinoma, larger tumor mass, metastasis and invasion. Univariate Kaplan-Meier analysis showed that increased expression of MTA1 and lowered expression of KAI-1 and KiSS-1 were significantly associated with decreased overall survival. Cox regression analysis showed that tumor mass, lymph node metastasis, invasion, and MTA1 expression levels negatively correlated with survival. CONCLUSIONS: Our study suggested that KAI-1, KiSS-1, and MTA1 might be important biological markers involved in the carcinogenesis, metastasis, and invasion of gallbladder adenocarcinoma, but MTA1 is an independent factor of prognosis.

[Study on the extraction technology of its flavonoids parts from Tricyrtis maculata growing in Shaanxi Province].

OBJECTIVE: To optimize the extraction technology of total flavonoids from Tricyrtis maculata. METHODS: With UV spectrophotometry as detection method and the content of total flavonoids as index,using single factor experiment and L9 (3(4)) orthogonal test, the optimal condition was deterined. RESULTS: The best extraction technology was as follows:soaked the medicinal materials for 15 minutes, water-decoted for 3 times, the solid-water ratio was 1:45, 1:40, 1:40 and the decotion time was 1, 0.5, 0.5 h respectively. CONCLUSION: The optimal extraction technology is reasonable and provides a basis for its further study.

Up-regulation of galectin-3 and Sambucus nigra agglutinin binding site is associated with invasion, metastasis and poor-progression of the gallbladder adenocarcinoma.

BACKGROUND/AIMS: To study the expression of galectin-3 (gal-3) and Sambucus nigra agglutinin (SNA) binding site and to detect their clinicopathological significances in the benign and malignant lesions of gallbladder. METHODOLOGY: We used immunohistochemistry to detect gal-3 expression and ABC affinity-cytochemistry to detect SNA binding site in specimens of adenocarcinoma, peritumoral tissues, polyp and chronic cholecystitis. RESULTS: The positive expression rates of gal-3 and SNA binding site were significantly higher in adenocarcinoma (62.0%, 66.7%) than those in peritumoral tissues (39.1%, 45.6%), polyp (26.7%, 33.3%) and chronic cholecystitis (11.4%, 11.4%) (p<0.05). A high consistency was found between the levels of expression of gal-3 expression and SNA binding site in adenocarcinoma (χ²=9.51, p<0.01). Univariate Kaplan-Meier analysis showed that increased expression of gal-3 (p=0.028) or SNA binding site (p=0.030) was associated with decreased overall survival. Multivariate Cox regression analysis showed that increased expression of gal-3 (p=0.012) or SNA binding site (p=0.030) was an independent prognostic predictor in gallbladder adenocarcinoma. CONCLUSIONS: These results suggest that expression of gal-3 and SNA binding site might have important effects on the carcinogenesis, progression and biological behaviors of gallbladder cancer.

Identification of CD146 expression, angiogenesis, and lymphangiogenesis as progression, metastasis, and poor-prognosis related markers for gallbladder adenocarcinoma.

Gallbladder cancers (GBC) are associated with high disease-specific mortality rates because of no means of early detection and effective therapies. In this study, we investigated CD146 expression, microvessel densities, and lymph vessel densities in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using immunohistochemistry. We demonstrated that positive CD146 expression, and average microvessel and lymph vessel counts in gallbladder adenocarcinomas were significantly higher than those in peritumoral tissues, polyps, and chronic cholecystitis (ps < 0.01). Positive CD146 expression, and average microvessel and lymph vessel counts were also significantly lower in cases with well-differentiated adenocarcinoma, maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues than in cases with poorly differentiated adenocarcinoma, maximal tumor diameter ≥ 2 cm, metastasis in lymph nodes, and invasion of regional tissues (p < 0.05 or p < 0.01). Univariate Kaplan-Meier analysis showed that increased expression of CD146 (p = 0.056), higher average microvessel counts (p < 0.05), and lymph vessel counts (p < 0.05) were associated with decreased overall survival. Multivariate Cox regression analysis showed that average microvessel and lymph vessel counts (ps < 0.05) were independent prognostic predictors in gallbladder adenocarcinoma. Our study suggested that the elevated expression of CD146, angiogenesis, and lymphangiogenesis might be closely related to progression, invasion, metastasis, and prognosis of gallbladder adenocarcinoma.