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To evaluate safety and efficacy of one- vs. two-session radiofrequency ablation (RFA) of parathyroid hyperplasia for patients with secondary hyperparathyroidism (SHPT) and to compare the outcome of both methods on hypocalcemia. Patients with secondary hyperparathyroidism underwent ultrasound guided RFA of parathyroid hyperplasia. Patients were alternately assigned to either group 1 (n = 28) with RFA of all 4 glands in one session or group 2 (n = 28) with RFA of 2 glands in a first session and other 2 glands in a second session. Serum parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) values were measured at a series of time points after RFA. RFA parameters, including operation duration and ablation time and hospitalization length and cost, were compared between the two groups. Mean PTH decreased in group 1 from 1865.18 ± 828.93 pg/ml to 145.72 ± 119.27 pg/ml at 1 day after RFA and in group 2 from 2256.64 ± 1021.72 pg/ml to 1388.13 ± 890.15 pg/ml at 1 day after first RFA and to 137.26 ± 107.12 pg/ml at 1 day after second RFA. Group 1’s calcium level decreased to 1.79 ± 0.31 mmol/L at day 1 after RFA and group 2 decreased to 1.89 ± 0.26 mmol/L at day 1 after second session RFA (P < 0.05). Multivariate analysis showed that hypocalcemia was related to serum ALP. Patients with ALP ≥ 566 U/L had lower calcium compared to patients with ALP < 566 U/L up to a month after RFA (P < 0.05). Group 1’s RFA time and hospitalization were shorter and had lower cost compared with Group 2. US-guided RFA of parathyroid hyperplasia is a safe and effective method for treating secondary hyperparathyroidism. Single-session RFA was more cost-effective and resulted in a shorter hospital stay compared to two sessions. However, patients with two-session RFA had less hypocalcemia, especially those with high ALP.

Background: Aspirin, with its pleiotropic effects such as anti-inflammatory and anti-platelet aggregation, has been widely used for anti-inflammatory, analgesic, and cardiovascular diseases. However, the association between the use of aspirin before the intensive care unit (ICU) and clinical outcomes in critically ill patients with acute kidney injury (AKI) is unknown. Methods: Patients with AKI in this retrospective observational study were selected from the Marketplace for Medical Information in Intensive Care IV (MIMIC-IV). The association between aspirin intervention and 30-day mortality was assessed using Cox proportional hazards model. Logistic regression models were used to assess the association of aspirin intervention with the risks of intracranial hemorrhage, gastrointestinal bleeding and blood transfusion. The propensity score matching (PSM) method was adopted to balance the baseline variables. Sensitivity analysis was performed to validate the results by multiple interpolations for the missing data. Results: The study included 4237 pre-ICU aspirin users and 9745 non-users. In multivariate models, we found a decreased risk of mortality in those who received aspirin before ICU compared to those who did not (30-day:hazard ratio [HR], 0.70; 95% CI, 0.62–0.79; p < 0.001; 90-day:HR, 0.70; 95% CI, 0.63–0.77, p < 0.001; 180-day:HR, 0.72; 95%CI,0.65–0.79, p < 0.001). This benefit was consistent in the post-PSM analyses, sensitivity analyses, and subgroup analyses. Moreover, aspirin intervention was associated with a reduced risk of intracranial hemorrhage and gastrointestinal bleeding (HR, 0.16; 95% CI, 0.10–0.25; p < 0.001; HR, 0.59; 95% CI, 0.38–0.88, p = 0.012) after being adjusted by relating covariates, whereas with a increased risk of blood transfusion (HR, 1.28; 95% CI, 1.16–1.46; p < 0.001). Conclusion: Patients with AKI treated with aspirin before ICU admission might have reduced 30-day, 90-day and 180-day mortality without increasing the risk of intracranial hemorrhage (ICH) or gastrointestinal bleeding, but may increase the risk of transfusion.

The aim of the present study to evaluate the application of sentinel lymph node (SLN) pathology in rectal cancer using ex vivo mapping and to investigate the incidence and prognostic value of occult SLN metastasis in routine node-negative specimens. Specimens (n=117) of rectal cancer were examined using a combination of routine pathology and ex vivo SLN mapping. The inspected SLNs were further treated with immunohistochemical staining for occult cancer foci. The log-rank test was used to assess survival. SLNs were examined in 112 of the included specimens with a total number of 212, resulting in an identification rate of 95.7% (112/117). The status of SLNs accurately reflected N stage in 93.8% (105/112) of cases and the sensitivity was 75.6% (31/41) in detecting nodal metastasis. The accuracy of SLN pathology decreased in cancers of more advanced TNM stages (P=0.001). In 74 cases with routine node-negative (N0) disease, SLN micrometastasis (MIC) and isolated tumor cells (ITC) were examined in 9 and 4 cases, while the remaining 61 were regarded as negative (NEG). The log-rank test revealed poorer disease-free and overall survival of the MIC group compared with the NEG group. However, the findings from the ITC group were not significant compared with those from the MIC and NEG groups. In conclusion, ex vivo SLN pathology is practical and accurate in rectal cancer; however, its utility is limited in cases of advanced disease. Immunohistochemically detected SLN micrometastasis in node-negative cases is therefore a predictor of poorer outcome, and may therefore be listed as a marker for adjuvant therapy.

Purpose The aim of this study was to evaluate the prevalence and clinical significance of caspase-10 mRNA expression in stage II colorectal cancer. Methods Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze caspase-10 expression in cancer tissue and corresponding normal mucosa from 120 patients with stage II colorectal cancer. Variables were analyzed by Chi-square test or Fisher’s exact test. Survival was evaluated with method of Kaplan–Meier. Multivariate analysis was performed with Cox’s proportional hazards model. Results The expression of caspase-10 mRNA was found to be downregulated in cancer tissue compared to normal mucosa ( P  = 0.001). Poorly differentiated cancer showed lower mRNA expression than cancer with greater differentiation ( P  = 0.031). Univariate survival curves, estimated using the method of Kaplan–Meier, defined a significant association between caspase-10 expression and both overall survival ( P  = 0.012) and disease-free survival ( P  = 0.021). A multivariate analysis, performed by Cox’s proportional hazards regression model, confirmed that a low caspase-10 expression was the only significant factor to predict poor prognosis in patients with stage II colorectal cancer. Conclusion Our data indicate that caspase-10 expression, measured by quantitative real-time RT-PCR, is a possible prognostic factor in patients with stage II colorectal cancer.

Objectives: To investigate the expression of caspase-8 and -10 in rectal adenoma, adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the relationship between their expression and clinicopathological parameters of rectal cancer. Methods: The expression of caspase-8 and -10 was determined by real-time RT-PCR and immunohistochemistry in 36 rectal adenomas, 93 rectal cancers and 93 corresponding normal rectal mucosa samples. Results: Compared with normal mucosa, the mRNA expression of caspase-8 was higher in adenomas (p = 0.003), while that of caspase-10 was lower in adenomas (p = 0.035) and cancers (p = 0.001). Immunohistochemical results showed caspase-8 up-regulation in adenomas (p = 0.014), and caspase-10 down-regulation in adenomas (p = 0.034) and cancers (p < 0.001) compared with normal mucosa samples. Cancers with poor differentiation had lower caspase-10 mRNA and protein levels than those with better differentiation (p = 0.041 and p = 0.046, respectively). The protein expression of caspase-8 and -10 was in accordance with the mRNA expression (p = 0.043 and p = 0.018, respectively). Conclusions: Caspase-8 expression was up-regulated in rectal adenomas. Caspase-10 expression was down-regulated in both rectal adenomas and cancers, and was further related to differentiation. Caspase-8 and -10 may be involved in the pathogenesis of rectal cancer.

Retinoic acid-induced 14 is a developmentally regulated gene induced by retinoic acid and is closely associated with NIK/NF-κB signaling. In the present study, we examined the effect of RAI14 on mTOR-mediated glial inflammation in response to inflammatory factors and chemical ischemia. A U87 cell model of LPS- and TNF-α-induced inflammation was used to investigate the role of RAI14 in glial inflammation. U87 cells were treated with siR-RAI14 or everolimus to detect the correlation between mTOR, RAI14, and NF-κB. CoCl2-stimulated U87 cells were used to analyze the effect of RAI14 on mTOR-mediated NF-κB inflammatory signaling under chemical hypoxia. LPS and TNF-α stimulation resulted in the upregulation of RAI14 mRNA and protein levels in a dose- and time-dependent manner. RAI14 knockdown significantly attenuated the level of pro-inflammatory cytokine via inhibiting the IKK/NF-κB pathway. Treatment with an mTOR inhibitor (everolimus) ameliorated NF-κB activity and IKKα/β phosphorylation via RAI14 signaling. Notably, RAI14 also enhanced mTOR-mediated NF-κB activation under conditions of chemical hypoxia. These findings provide significant insight into the role of RAI14 in mTOR-induced glial inflammation, which is closely associated with infection and ischemia stimuli. Thus, RAI14 may be a potential drug target for the treatment of inflammatory diseases.

Aim To investigate the relationship between the positioning of the lower central incisor and physical morphology of the surrounding alveolar bone. Methodology Thirty-eight patients （18 males, 20 females）, with mean age of 13.4 years, were included in this study. As part of orthodontic treatment planning the patients were required to take dental Cone-beam CT （CBCT） covering the region of lower incisors, the sur- rounding alveolar bone and the mandibular symphysis. The cephalometric parameters were designed and measured to indicate the inclination of lower central incisor and physical morphology of the adjacent alveolar bone. Computer-aided descriptive statistical analysis was performed using SPSS 15.0 software package for Windows. A correlation analysis and a linear regression analysis between the incisor inclination and the alveolar bone morphology were performed. Results Significant positive correlations were found between the lower central incisor inclination and the morphological contour of the alveolar bone （P〈0.05）. The lower central incisor root apex was closer to the lingual alveolar crest when it was buccally inclined. Conclusion The morphology of the alveolar bone may be affected by incisal inclination.

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1 H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions. The interaction between a GPCR, such as the vasopressin receptor-2 (V2R), and arrestin depends on the receptors’ phosphorylation pattern. Here authors use FRET and NMR to analyze the phosphorylation patterns of the V2R-arrestin complex and show that phospho-interactions are the key determinants of selective arrestin conformational states and correlated functions.

Calcium is an important integrative component of the human body and critical for human health. It has been well established that calcium intake is helpful in the prevention and treatment of osteoporosis, which has become one of the most serious public health problems across the world. However, community-dwelling adults with and without osteoporosis are rarely concerned or even not aware of the potential side effects of high or inappropriate doses of calcium intake. Some recent studies have revealed that excessive calcium intake might increase the risks of cardiovascular diseases. The purpose of this article was to review the health benefits, costs, and consequences of calcium supplementation on osteoporosis/osteoporotic fractures, cardiovascular events, kidney stones, gastrointestinal diseases, and other important diseases. In the end, we suggest that calcium supplementation should be prescribed and taken cautiously, accounting for individual patients' risks and benefits. Clearly, further studies are needed to examine the health effects of calcium supplementation to make any solid recommendations for people of different genders, ages, and ethnicities.