[3D-printed vertebral body in anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma].

OBJECTIVE: To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data. RESULTS: There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01). CONCLUSION: 3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.

Effect of γ-secretase inhibitor on Treg in PBMC of respiratory syncytial virus bronchiolitis children.

Bronchiolitis is a widespread lower respiratory tract infection in infants and young children, and is closely related to the incidence of asthma, and T regulatory cells (Tregs) play a role in its pathogenesis.

[Treatment of subcutaneous fistula secondary to cerebrospinal fluid leakage in thoracic spinal stenosis cases].

OBJECTIVE: To investigate the treatment strategy for subcutaneous fistula secondary to cerebrospinal fluid leakage (CSFL) in thoracic spinal stenosis (TSS) cases. METHODS: In the study, 186 CSFL cases diagnosed with TSS and operated in general spine group of Department of Orthopedics, Peking University Third Hospital from January 2005 to December 2014 were retrospectively reviewed, of which eleven had subcutaneous fistula secondary to CSFL and were regularly followed up. Treatment strategy for subcutaneous fistula depended on the severity of CSFL and the recovery rate of thoracic myelopathy. Japanese Orthopedic Association (JOA) score was utilized to evaluate the neurologic status of these patients preoperatively and postoperatively. Statistical analysis was conducted between preoperative and postoperative JOA scores. RESULTS: All of the 11 patients were regularly followed up for at least 24 months. Six of them had ossification of the posterior longitudinal ligament (OPLL) combined with ossification of ligamentum flavum (OLF), all of them undertook "cave-in" 360° circumferential decompression of the spinal cord with instrumentation. Five cases had OLF only, and received En bloc resection of lamina and OLF and fixation. The follow-up period ranged from 30 months to 131 months, and averaged at (85±34) months. Preoperative symptoms lasted from 3 months to 8 years, and the median was 18 months. Drainages were placed for 2-6 days, and averaged at (4.2±1.1) days. Ten cases appeared with fever during the perioperative period, the maximum body temperature was (37.3-39.7) °C. Prolonged antibiotics were applied in two cases with high fever. Ten cases were treated with conservative methods, CSFL were completely absorbed during the follow-up time, of which compressive dressing was utilized in 8 cases, and punctures combined with compressive dressing were used in 2 cases. For only 1 case, conservative therapy failed and reoperation was required because of neurological deterioration arising from CSF pseudocyst. For these 11 cases, preoperative JOA score arose from (3.8±1.6) preoperatively to (8.9±1.2) at the end of the final follow-up, the recovery rate was 70.8%. No infection of wound or central nerve system were noticed, and neither were unhealing wound. CONCLUSION: Most TSS cases with subcutaneous fistula secondary to CSFL could be cured by conservative methods, and reoperation is required only if myelopathy caused by cerebrospinal fluid pseudocyst is identified.

Classification and regression tree analysis of acute-on-chronic hepatitis B liver failure: Seeing the forest for the trees.

At present, there is no ideal model for predicting the short-term outcome of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). This study aimed to establish and validate a prognostic model by using the classification and regression tree (CART) analysis. A total of 1047 patients from two separate medical centres with suspected ACHBLF were screened in the study, which were recognized as derivation cohort and validation cohort, respectively. CART analysis was applied to predict the 3-month mortality of patients with ACHBLF. The accuracy of the CART model was tested using the area under the receiver operating characteristic curve, which was compared with the model for end-stage liver disease (MELD) score and a new logistic regression model. CART analysis identified four variables as prognostic factors of ACHBLF: total bilirubin, age, serum sodium and INR, and three distinct risk groups: low risk (4.2%), intermediate risk (30.2%-53.2%) and high risk (81.4%-96.9%). The new logistic regression model was constructed with four independent factors, including age, total bilirubin, serum sodium and prothrombin activity by multivariate logistic regression analysis. The performances of the CART model (0.896), similar to the logistic regression model (0.914, P=.382), exceeded that of MELD score (0.667, P<.001). The results were confirmed in the validation cohort. We have developed and validated a novel CART model superior to MELD for predicting three-month mortality of patients with ACHBLF. Thus, the CART model could facilitate medical decision-making and provide clinicians with a validated practical bedside tool for ACHBLF risk stratification.

Serotonergic antidepressant use and the risk of fracture: a population-based nested case-control study.

UNLABELLED: This is the first study to investigate the association between the use of selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) and the risk of fractures using a nationwide representative cohort of ethnic Chinese. Current use of SSRI/SNRI and the co-morbidity, especially osteoporosis and history of falling, play an important role in the increased risk of fractures. INTRODUCTION: This nested case-control study examines the association between the timing, intensity, and individual components of serotonergic antidepressant (including SSRIs and SNRIs) use and the risk of all-cause fracture. METHODS: Using the 2002-2011 Taiwan National Health Insurance Research Database, we identified patients who received at least three prescriptions of antidepressants between January 1st 2002 and December 31st 2010 as our study cohort. In the study cohort, we identify 8250 patients who had first admission for fracture and 33,000 matched controls (1:4, matched by age, sex, and cohort entry date). Multivariate conditional logistic regression was used to estimate the association between the use of serotonergic antidepressants and the risk of fracture. RESULTS: Current users of serotonergic antidepressants were associated with an increased risk of fracture (adjusted odds ratio (aOR) 1.16 [95 % confidence interval 1.07-1.25]). Furthermore, a higher risk of fractures was found in patients with osteoporosis (aOR 3.05 [2.73-3.42]) or a history of falling (aOR 6.13 [3.41-11.0]). The risks of fracture between SSRI and SNRI users were comparable. CONCLUSION: Current use of SSRI/SNRI is associated with an increased risk of all caused fractures. Additionally, the co-morbidity, especially osteoporosis and a history of falling, plays an important role in the risk of fractures.

[The change of vaginal lactobacillus in patients with high-risk human papillomavirus infection].

OBJECTIVE: To study the distribution characteristics of lactobacillus in the vaginal mucosa of patients with HPV infection. METHODS: The planting density of lactobacillus in vaginal secretions of 95 cases with HPV16/18 infection and 90 cases of normal women of childbearing age were observed by oil microscope. And the strains of vaginal lactobacilli in two groups were analyzed using species-specific polymerase chain reaction (Species-specific PCR) and the distribution of vaginal lactobacilli in patients with HPV16/18 infection were investigated. RESULTS: In HPV16/18 infective groups, the planting density of lactobacillus in the vaginal mucosa was 104 (68-186)/HP. It was significantly lower than that of the normal group (234 (161-326)/HP, P<0.05). Compared with the normal group, the positive rates of lactobacillus iners, lactobacillus crispatus, and lactobacillus gasseri were significantly lower in HPV16/18 infection group (P<0.05). CONCLUSION: The HPV16/18 infection is associated with the decreased number of lactobacillus and the imbalance of vaginal flora; Lactobacillus iners, lactobacillus crispatus, and lactobacillus gasseri may play a key role in maintaining the vaginal micro ecological environment.

Adherence and medication utilisation patterns of fixed-dose and free combination of angiotensin receptor blocker/thiazide diuretics among newly diagnosed hypertensive patients: a population-based cohort study.

OBJECTIVE: The study aimed to compare the adherence and persistence among newly diagnosed hypertensive patients using fixed-dose (FDC) and free combinations (FC) of angiotensin receptor blocker (ARB)/thiazide diuretic using Taiwan's National Health Insurance Research Database. METHODS: General linear regression and Kaplan-Meier analyses were used to estimate the impact of FDC on adherence [measured by medication possession ratio (MPR)] and persistence (time from day of initiation to treatment discontinuation) of ARB/thiazide diuretic. RESULTS: The adjusted MPRs were all significantly higher among FDC group compared with FC group (6 months: 66.55% vs. 63.86%; 1 year: 52.58% vs. 46.73%, 1.5 year: 46.30% vs. 38.07%; 2 year: 42.06% vs. 32.45%, all p < 0.001). Patients received FDC therapy were less likely to discontinue their therapy [adjusted hazard ratio (HR) 0.79, 95% CI = 0.74-0.85]. CONCLUSIONS: Our findings suggest that use of FDC is associated with higher adherence and persistence rates than use of FC in newly diagnosed hypertensive patients.

Interleukin-10 polymorphisms and nasopharyngeal carcinoma risk: a meta-analysis.

It has been reported that interleukin-10 (IL-10) promoter genes (1082 A/G, 819 T/C, 592 A/C) are associated with nasopharyngeal carcinoma (NPC). However, the results remain controversial and ambiguous. To resolve inconsistencies in published data, we performed a meta-analysis to ascertain the association between IL-10 polymorphisms and NPC risk. Two case-control studies and two cohort studies were quantitatively analyzed to evaluate IL-10 promoter gene polymorphisms and NPC risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for each genetic model and allelic comparison. A random-effect model or a fixed-effect model was used to calculate the overall combined risk estimates. Overall, the variant genotypes (AA and AG) of the IL-10-1082 A/G polymorphism were associated with elevated risk of NPC compared with the GG homozygote (AG vs GG: OR = 1.77; 95%CI = 1.39-2.26; AG + GG vs AA: OR = 1.78; 95%CI = 1.42-2.22); no significant associations were observed in allelic contrast and the recessive model. Strong positive association was seen in the cohort studies but not in the case-control studies. No statistically significant association was detected between IL-10-819 T/C and IL-10-592 A/C polymorphisms and NPC. Additionally, publication bias was not found. Based on the current evidence, this meta-analysis suggests that IL-1082 A/G polymorphism may increase the risk of NPC, but IL-10-819 T/C and IL-10-592 A/C polymorphisms do not. Further multicenter studies that are better controlled are required to confirm these findings.

Orolingual angioedema after alteplase therapy of acute ischaemic stroke: incidence and risk of prior angiotensin-converting enzyme inhibitor use.

BACKGROUND AND PURPOSE: Orolingual angioedema (OA) is an uncommon but potentially life-threatening complication of treatment with recombinant tissue plasminogen activator (rt-PA; alteplase) during acute ischaemic stroke. This study aimed to determine the incidence of rt-PA-related OA in an Asian stroke population and the risk of pre-stroke anti-hypertensive drug use for development of this complication. METHODS: A multi-center stroke registry was used to identify the pre-stroke medications of acute ischaemic stroke patients receiving intravenous rt-PA from January 2002 to December 2013. The clinical manifestations of rt-PA-related OA were recorded and the incidence of this complication was determined. The risks of pre-stroke use of different anti-hypertensive agents for the occurrence of rt-PA-related OA were determined from this study and from a meta-analysis. RESULTS: A total of 559 patients received intravenous rt-PA over a 12-year period. Five patients (two males) developed OA after rt-PA administration. The incidence of OA amongst these patients was 0.89% (95% confidence interval 0.29%-2.09%), which was lower than that obtained by meta-analysis (1.9%). Amongst pre-stroke anti-hypertensive medications, angiotensin-converting enzyme (ACE) inhibitors were found in this study to have the highest relative risk for rt-PA-related OA (17.1; 95% confidence interval 3.0-96.9). Meta-analysis also revealed that pre-stroke use of ACE inhibitors was associated with a high relative risk of OA after intravenous rt-PA (12.9; 95% confidence interval 4.5-37.0). CONCLUSIONS: The incidence of rt-PA-related OA in the Asian population is lower than that in the Caucasian population. Pre-stroke use of ACE inhibitors significantly increases the risk of this complication.

Interleukin-1ß +3954 polymorphisms and risk of external apical root resorption in orthodontic treatment: a meta-analysis.

The purpose of this meta-analysis was to determine whether genetic variants of the interleukin-1ß[+3954 C>T (rs1143634)] (IL-1ß +3954 C>T) gene polymorphisms were associated with orthodontic external apical root resorption (EARR). A meta-analysis was carried out using data entered into the PubMed and Embase electronic databases before October 5, 2012. A total of 7 studies were identified for meta-analysis. The strength of the relationship between IL-1ß +3954 C>T polymorphism and the risk of EARR was assessed using odds ratio (OR). The studies provided overall OR estimates for EARR. Overall, the variant genotypes (CC and CT) of the IL-1ß +3954 C>T polymorphism were unassociated with EARR risk compared with the TT homozygote [CC vs TT, OR = 1.28, 95% confidence interval (95%CI) = 0.27-6.08; CT vs TT, OR = 0.74, 95%CI = 0.11-5.02]. Similarly, no associations were found in the dominant and recessive models (dominant model, OR = 1.08, 95%CI = 0.24-4.86; recessive model, OR = 1.85, 95%CI = 0.87-3.93). No publication bias was found, and no association was apparent between the IL-1ß +3954 C>T polymorphism and risk of EARR in orthodontic treatment patients. Further multicenter and better-controlled studies are required to confirm these findings.

Effects of Selenium Supplementation on the Ion Homeostasis in the Reproductive Organs and Eggs of Laying Hens Fed With the Diet Contaminated With Cadmium, Lead, Mercury, and Chromium.

The objective of this study was to explore the toxic effects of different heavy metals in combination with their deposition and ion homeostasis in the reproductive organs and eggs of laying hens, as well as the alleviating action of selenized yeast. A total of 160 Lohmann pink-shell laying hens (63-week-old) were randomly allocated into four treatments with 10 replicates of four hens each. The four dietary treatments were the corn-soybean meal basal dietary (control; CON); the CON dietary supplemented with 0.4 mg/kg selenium from selenized yeast (Se); the CON dietary supplemented with 5 mg/kg Cd + 50 mg/kg Pb +3 mg/kg Hg + 5 mg/kg Cr (HEM), and the HEM dietary supplemented with 0.4 mg/kg selenium from selenized yeast (HEM+Se). The dietary HEM significantly increased Cd, Pb, and Hg deposition in the egg yolk and ovary, and Cd and Hg deposition in the oviduct and in the follicular wall (p < 0.05). The HEM elevated Fe concentration in the egg yolk, ovary, and oviduct (p < 0.05). The HEM decreased Mn concentration in the egg yolk, Fe, Mn, and Zn concentrations in the egg white, Cu concentration in the ovary, Mg concentration in the oviduct, as well as Ca, Cu, Zn, and Mg concentrations in the follicular walls (p < 0.05). Dietary Se addition elevated Se concentration in the egg yolk, oviduct, and follicular walls and Mg concentration (p < 0.05) in the oviduct, whereas it reduced Fe concentration in the oviduct compared with the HEM-treated hens. Some positive or negative correlations among these elements were observed. Canonical Correlation Analysis showed that the concentrations of Pb and Hg in the egg yolk were positively correlated with those in the ovary. The concentration of Cd in the egg white was positively correlated with that in the oviduct. In summary, dietary Cd, Pb, Hg, and Cr in combination caused ion loss and deposition of HEM in reproductive organs of laying hens. Dietary Se addition at 0.4 mg/kg from selenized yeast alleviated the negative effects of HEM on Fe and Mg ion disorder in the oviduct and follicle wall of hens.

Macrophages Promote Growth of Squamous Cancer Independent of T cells.

Oral cancers, primarily squamous cell carcinomas (SCCs), progress either slowly or aggressively. Here we assessed the role of macrophages in SCC behavior. We used mouse SCC cells derived from tumors harboring a KrasG12D activation mutation and Smad4 deletion in keratin 15-positive stem cells and a human oral SCC cell line, FaDu, which has NRAS amplification and SMAD4 deletion. SCC cells were transplanted into immune-compromised or immune-competent (syngeneic) recipients. After tumors were established, we used clodronate liposomes to ablate macrophages. We found that the number of tumor-associated macrophages (TAMs) was not affected by the presence of T cells but differed considerably among tumors derived from different SCC lines. Clodronate significantly reduced TAMs and splenic macrophages, resulting in reduced SCC volumes. Tumors with clodronate treatment did not show decreased proliferation but did exhibit increased apoptosis and reduced vascular density. FLIP (Fas-associated via death domain-like interleukin 1ß-converting enzyme inhibitory protein), an apoptosis inhibitor abundantly produced in tumor cells and TAMs, was reduced in tumor cells of clodronate-treated mice. Reduced FLIP levels correlated with reductions in phosphorylated nuclear NFκB p65 and NFκB inhibitor attenuated FLIP protein levels in SCC cells. Furthermore, TGFß1 serum levels and pSmad3 were reduced in clodronate-treated mice, but their reductions were insufficient to reverse epithelial-mesenchymal transition or TGFß-mediated angiogenesis in endothelial cells. Consequently, metastasis was not significantly reduced by macrophage reduction. However, reduced pSmad3 correlated with reduction of its transcriptional target, vascular endothelial growth factor A, in clodronate-treated tumor cells, which correlated with reduced vascular density in clodronate-treated tumors. Taken together, our study revealed that macrophages contribute to SCC expansion through interactions with tumor cells but are dispensable for SCC metastasis. Our study provides novel insights into understanding the contributions and limitations of TAMs in SCC progression.

Euxanthone exhibits anti-proliferative and anti-invasive activities in hepatocellular carcinoma by inducing pyroptosis: preliminary results.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths. Euxanthone, a xanthone compound extracted from Polygala caudata, possesses a variety of pharmacological activities. This work aimed to explore whether euxanthone exhibits anti-cancer activities in HCC. PATIENTS AND METHODS: Tissue specimen was collected and the mRNA and protein expression of marker proteins were detected by qRT-PCR and Western blot, respectively. The viable cell number was assessed by CCK-8 assay. TUNEL assay was utilized to determine cell death. Cell migration was measured by Wound healing. Cell invasion was measured by transwell assay. Xenograft model was established to evaluate the efficacy of euxanthone in vivo. RESULTS: We demonstrated that HCC tissue and HCC cell line presented with lower expression of caspase-1, IL-1ß, and IL-18. Euxanthone markedly suppressed the proliferation of HCC cells and induced cell death. In addition, euxanthone inhibited cell migration and invasion. Meanwhile, our results showed that euxanthone promoted cell death in a caspase-2 dependent manner. In vivo data also showed that euxanthone suppressed tumor growth and promoted pyroptotic cell death. CONCLUSIONS: We showed that that euxanthone may be a candidate of anticancer agent and provide clinical benefits for patients with HCC.

Atorvastatin improves plaque stability in diabetic atherosclerosis through the RAGE pathway.

OBJECTIVE: To study the improving effect of atorvastatin on plaque stability in diabetes mellitus (DM) mice complicated with atherosclerosis. MATERIALS AND METHODS: Apolipoprotein E (ApoE)-/- mice were used to establish the DM mouse model. Half of the mice received atorvastatin after successful modeling. ApoE-/- and C57BL/6J mice were used as controls. Oil red O staining and Masson staining were performed to detect the lipid and collagen components in mice. Immunohistochemical assay was used to observe the expressions of smooth muscle cell (SMC) and Ly-6c. The expressions of receptor for advanced glycation end products (RAGE), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-κB (NF-κB) in tissues were detected by Western blotting. Finally, the levels of serum soluble RAGE (sRAGE), advanced glycation end products (AGEs), malondialdehyde (MDA) and reduced glutathione (GSH) in mice were also detected. RESULTS: Atorvastatin reduced the area of atherosclerotic plaque and improved the stability of arterial plaque through reducing lipid deposition, the number of macrophages and SMC, increasing collagen fibers. In mice in atorvastatin group, the levels of serum AGEs and sRAGE were decreased. Moreover, atorvastatin inhibited the downstream pathway of RAGE as well as DM, thus inducing the oxidative stress. CONCLUSIONS: Atorvastatin improves plaque stability in diabetic atherosclerosis through the RAGE pathway.

Influence of everolimus on cyclosporine Neoral pharmacokinetics in Chinese de novo cardiac transplant recipients.

OBJECTIVE: This study sought to determine the influence of everolimus on cyclosporine Neoral (CsA) pharmacokinetics over the first 6 months after heart transplantation in Chinese recipients. METHODS: Six de novo cardiac recipients receiving a CsA-everolimus-based immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction were compared with six age-matched recipients receiving a CsA-azathioprine-based regimen. We compared CsA 12-hour area-under-curve (AUC) of the first dose (PK-1) and steady state dose (PK-S) at 1 month after transplantation. The CsA trough concentrations (Cmin) were compared over the first 6 months after transplantation. RESULTS: There was no significant difference between the two groups in age, gender, and body weight. With respect to dose-normalized CsA AUC(0-infinity) of PK-1 and dose-normalized CsA AUC(0-12) of PK-S, the difference between the everolimus- and the azathioprine-based regimens was not significant. The dose-normalized CsA trough concentrations (Cmin/dose) were significantly lower in the everolimus-based group than in the azathioprine-based group during the first 5 months after heart transplantation, but the difference was not significant at posttransplantation month 6. CONCLUSIONS: When CsA pharmacokinetic profiles were considered, the CsA dose requirement was not lower in Chinese patients receiving everolimus than that in patients receiving azathioprine. The results differed from reports from Western countries.

Therapeutic drug monitoring of cyclosporine Neoral in de novo Chinese cardiac transplant recipients treated with an everolimus-cyclosporine immunosuppressive regimen.

UNLABELLED: This study determined cyclosporine Neoral (CsA) pharmacokinetics and the accuracy of a limited sampling strategy to predict the 12-hour CsA area-under-the-curve (AUC) to provide a practical method for more accurate therapeutic drug monitor of CsA among de novo Chinese heart transplant recipients treated with an everolimus-CsA immunosuppressive regimen. METHODS: Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after oral administration of CsA in six de novo heart recipients receiving a CsA, everolimus, and methylprenisolone immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction. We analyzed the pharmacokinetics of the first dose (PK-1) and steady state dose (PK-2) at 1 month after transplantation. The accuracy of a single-point sampling method to predict the AUC was generated by linear regression analyses. RESULTS: The t(max) and dose-normalized C(max) of PK-1 and PK-2 were similar. The correlations in single-point blood levels of PK-1 to predict the AUC(0-infinity) were much lower than the corresponding sampling times in PK-2. In PK-2 study, C4 had the best correlation (r(2) = 0.913, P = .003) to predict AUC(0-12). In addition, the trough concentrations, C(0) (r(2) = 0.875, P = .006) and C(12) (r(2) = 0.783, P = .02) also showed good correlations. C2 had insufficient correlation to predict AUC(0-infinity) in PK-1 or AUC(0-12) in the PK-2 study. In conclusion, the absorption of CsA was similar during PK-1 and PK-2. At steady dose, C4 had the best single-point correlation to predict AUC(0-12). Trough blood levels may be more practical in clinical use to monitor CsA.

Study on JNK/AP-1 signaling pathway of airway mucus hypersecretion of severe pneumonia under RSV infection.

OBJECTIVE: To investigate the JNK/AP-1 signaling pathway of airway mucus hypersecretion of severe pneumonia under respiratory virus (RSV) infection. PATIENTS AND METHODS: Total of 56 severe pneumonia children under RSV infection were selected. Reverse transcription polymerase chain reaction (RT-PCR) was performed to measure the expression quantity of MUC5B mRNA and MUC5AC mRNA, and ELISA was used to measure the expression quantity of MUC5AC and MUC5B proteins. Following that, the children were divided into airway mucus hypersecretion group (n = 37) and non-hypersecretion group (n = 19). Western blotting was performed to detect the expression levels of JNK1/2, p-JNK1/2 and AP-1 proteins. RESULTS: Expression of MUC5AC and MUC5B proteins, and MUC5AC mRNA and MUC5B mRNA in the airway mucus hypersecretion group were significantly higher than those in the non-hypersecretion group (p < 0.05). The expression levels of JNK1/2, p-JNK1/2 and AP-1 proteins in airway mucus hypersecretion group were higher than those in the non-hypersecretion group (p < 0.05). CONCLUSIONS: MUC5AC and MUC5B can be used as marker molecules of airway mucus hypersecretion. Airway mucus hypersecretion of severe pneumonia induced by RSV might be related to the activation of JNK/AP-1 signaling pathway.

Computed tomography versus magnetic resonance imaging for diagnosing cervical lymph node metastasis of head and neck cancer: a systematic review and meta-analysis.

Computed tomography (CT) and magnetic resonance imaging (MRI) are common imaging methods to detect cervical lymph node metastasis of head and neck cancer. We aimed to assess the diagnostic efficacy of CT and MRI in detecting cervical lymph node metastasis, and to establish unified diagnostic criteria via systematic review and meta-analysis. A systematic literature search in five databases until January 2014 was carried out. All retrieved studies were reviewed and eligible studies were qualitatively summarized. Besides pooling the sensitivity (SEN) and specificity (SPE) data of CT and MRI, summary receiver operating characteristic curves were generated. A total of 63 studies including 3,029 participants were involved. The pooled results of meta-analysis showed that CT had a higher SEN (0.77 [95% confidence interval {CI} 0.73-0.87]) than MRI (0.72 [95% CI 0.70-0.74]) when node was considered as unit of analysis (P<0.05); MRI had a higher SPE (0.81 [95% CI 0.80-0.82]) than CT (0.72 [95% CI 0.69-0.74]) when neck level was considered as unit of analysis (P<0.05) and MRI had a higher area under concentration-time curve than CT when the patient was considered as unit of analysis (P<0.05). With regards to diagnostic criteria, for MRI, the results showed that the minimal axial diameter of 10 mm could be considered as the best size criterion, compared to 12 mm for CT. Overall, MRI conferred significantly higher SPE while CT demonstrated higher SEN. The diagnostic criteria for MRI and CT on size of metastatic lymph nodes were suggested as 10 and 12 mm, respectively.

Seizure after lidocaine for bronchoscopy: case report and review of the use of lidocaine in airway anesthesia.

Lidocaine-induced seizures have been reported after topical administration. A 30-year-old, 48-kg women with acquired immunodeficiency syndrome, chronic end-stage renal failure, anemia, congestive heart failure (CHF), cardiomyopathy, and increased liver function tests was admitted to the hospital with fever, chills, and dry cough. Bronchoscopy was performed to rule out Pneumocystis carinii pneumonitis; the patient experienced seizure activity after administration of a total dose of topical lidocaine 300 mg. Plasma drug concentration measured shortly after seizure, and at 4 and 22 hours after seizure were 12.0, 7.6, and 1.4 mg/L, respectively. A direct correlation exists between clinical symptoms and blood level of lidocaine; as the level increases to 8-12 mg/L the probability of seizure increases. The extent of absorption and bioavailability after airway administration depends on tissue vascularity, sites and techniques of application, patient's disease state, and, most important, the dose/unit body weight. The lidocaine dose should be titrated slowly and patients monitored for altered mental status. The dose often has to be decreased empirically in patients with liver disease or CHF. Efforts should be made to deliver minimum amounts of the drug to the lower respiratory tract, since its pharmacokinetics at that site are similar to those with intravenous administration.

Hemodynamic changes during acute pancreatitis and the dopamine therapy.

A dog model was used to measure the hemodynamic changes in acute pancreatitis (AP) caused by intraductal injection of fresh trypsin-bile mixture and to investigate the efficacy of dopamine in the treatment of AP. Dopamine was administered intravenously for 3 hours at a dose of 0.6 mg/kg/hour starting 10 min after the induction of AP. Hemorrhagic pancreatitis was characterized by a fall in cardiac output (CO), systemic arterial pressure (SAP), an increase in pulmonary vascular resistance (PVR), systemic vascular resistance (SVR) and the development of early reduction of pancreatic blood flow (PBF). Administration of dopamine produced a significant increase in PBF and leads to a normalization in CO, SAP, PVR and SVR. In addition, dopamine significantly reduced the severity of the AP, as assessed by histological staging and mortality rate. These results suggest that dopamine can limit the progression from edematous to hemorrhagic pancreatitis and prevent irreversible pancreatic damage through preserving PBF at the early phase of AP.