[Establishment of a prognostic nomogram and discussion on optimal treatment for cervical adenocarcinoma:a retrospective study based on SEER database and Chinese single-center data].

Objective: To establish and validate a predicting nomogram for cervical adenocarcinoma based on surveillance, epidemiology and end results (SEER) database and Chinese single-center data, and to explore the optimal treatment for cervical adenocarcinoma. Methods: This study selected 2 478 cervical adenocarcinoma patients from the SEER database as the training cohort, and 195 cervical adenocarcinoma patients from Cancer Hospital of Dalian University of Technology, Liaouing Cancer Hospital and Institute as an external validation cohort. Clinicopathological information and follow-up data of the two cohorts were collected. The radiotherapy group was defined as receiving comprehensive treatment based on concurrent chemoradiotherapy after initial diagnosis, while the surgery group was defined as receiving comprehensive treatment based on radical surgery. Log-rank test and cox regression were used to evaluate factors affecting the prognosis of cervical adenocarcinoma patients. A nomogram was drawn to predict the 3-year and 5-year overall survival rates of cervical adenocarcinoma patients, and then internal validation of the training cohort from SEER database and external validation of the hospital cohort were conducted. Results: (1) In the SEER database training cohort, there were 385 patients (15.54%, 385/2 478) in the radiotherapy group and 2 093 patients (84.46%, 2 093/2 478) in the surgery group. Overall survival time of the radiotherapy group was (55.8±51.3) months, while that of the surgery roup was (94.4±61.7) months, the difference between the two groups was statistically significant (χ2=256.44, P<0.001). Log-rank test showed that age, marital status, maximum of tumor diameters, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and treatments were all significant factors affecting the overall survival time of cervical adenocarcinoma patients (all P<0.001). Multivariate Cox regression analysis showed that elder (>50 years old), single status, huge tumors (>4 cm), high pathological grades (G2, G3), and advanced FIGO stages (≥Ⅱa2 stage) were independent risk factors for the overall survival time of cervical adenocarcinoma patients (all P<0.05); compared with radiotherapy, surgery was a protective factor for the prognosis of cervical adenocarcinoma patients (HR=0.619, 95%CI: 0.494-0.777; P<0.001). Further analysis of locally advanced stage and Ⅲc stage of patients showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm (HR=0.414, 95%CI: 0.182-0.942; P=0.036) in locally advanced stage and Ⅲc T1 to T2 stage (HR=0.473, 95%CI: 0.307-0.728; P=0.001). (2) The external validation cohort consisted of 39 patients (20.00%, 39/195) in the radiotherapy group and 156 patients (80.00%, 156/195) in the surgery group. The overall survival time of patients in the radiotherapy group was (51.7±34.3) months, while that of the surgery group was (63.1±26.6) months (χ2=28.41, P<0.001). Further analysis was conducted on locally advanced stage and Ⅲc stage patients, and multivariate Cox regression analysis was performed after propensity score matching, which showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm in locally advanced stage (HR=0.141, 95%CI: 0.023-0.843; P=0.032) and Ⅲc T1 to T2 stage (HR=0.184, 95%CI: 0.036-0.947; P=0.043). (3) Establishment and internal and external validation of nomogram: based on the six factors screened out by the multivariate Cox regression model, the nomogram was developed to predict the prognosis of cervical adenocarcinoma patients. The consistency index of the internal and external validation were 0.801 and 0.766, respectively, and the calibration curves matched well with the ideal fitting line. Conclusions: The key to the treatment of cervical adenocarcinoma is to prioritize radical surgery for patients with conditions for radical tumor resection. Compared with concurrent chemoradiotherapy, patients with locally advanced stages (Ⅰb3, Ⅱa2), and Ⅲc (T1, T2) stages cervical adenocarcinoma could benefit from comprehensive treatment based on radical surgery. The nomogram of this study has been validated internally and externally, and show good survival prediction efficacy for cervical adenocarcinoma patients.

[Association between abnormal oral glucose tolerance test patterns in the second trimester and large for gestational age newborns].

Objective: To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries. Methods: General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared. Results: (1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group (OR=1.76, 95%CI: 1.50-2.08; P<0.001), GDM 0+1 group (OR=2.29, 95%CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group (OR=1.98, 95%CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant (P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions: In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

Ingestion of Lactobacillus helveticus WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice.

Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.

[Research progress on physiological changes caused by wearing N95 mask in patients with chronic obstruction pulmonary disease].

N95 mask has been shown to reduce lower airway infections requiring hospitalization, mortality and exacerbation frequency in patients with chronic obstructive pulmonary disease(COPD), and therefore is recommended for all COPD patients by guidelines. However, the coverage of influenza vaccination in Chinese COPD patients is far from satisfactory. The large-scale COVID-19 vaccination may have a positive impact on the attitude towards influenza vaccines, and healthcare professionals should take active measures to improve the physical activation in patients with COPD.

[Effects of dexmedetomidine on injury of lungs and CHOP protein expression in elderly patients with lung cancer during one-lung ventilation].

Objective: To evaluate the effect of dexmedetomidine on lung injury and CCAAT/enhancer-binding protein homologous protein (CHOP) expression in elderly patients with lung cancer undergoing thoracoscopic lobectomy. Methods: A total of 120 elderly patients with lung cancer who underwent elective thoracoscopic lobectomy were selected from the Second Affiliated Hospital of Zhengzhou University from October 2018 to March 2019. The random phenotype was divided into dexmedetomidine group (group D, n=60) and control group (group C, n=60). The elapsed time before postoperative awake and spontaneous breathing recovery and agitation occurrence were recorded. The mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SPO(2)), oxygen partial pressure (PaO(2)), alveolar-arterial oxygen partial pressure difference[P(A-a)O(2)], end-tidal carbon dioxide partial pressure (P(ET)CO(2)), and airway pressure peak (P(peak)) were recorded before the anesthetic induction (T(0)), immediately after tracheal intubation (T(1)), immediately after unilateral pulmonary ventilation(T(2)), 1 hour after unilateral pulmonary ventilation (T(3)), immediately after bilateral pulmonary ventilation (T(4)), and at the end of surgery(T(5)). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, IL-10, super oxide dismutase (SOD) and malondialdehyde (MDA)were compared at the time of T(0), T(1), T(2), T(3), T(4) and T(5) in two groups. The ratios of alveolar damage (IQA), apoptotic index (AI), and the expression of CHOP mRNA and their protein in lung tissue were detected. Results: The recovery time of conscious and spontaneous breathing in group D were significantly shorter than that in group C (P<0.05). The MAP and HR of the two groups at T(1)-T(5) were significantly lower than those at T(0)(P<0.05).The levels of P(peak) in group C at T(3)-T(5) was significantly higher than those in group D (P<0.05). The SpO(2) values in the group D at T(1)-T(5) were significantly higher than those in group C (P<0.05). The P(A-a)O(2) values in the group D at T(1)-T(5) was significantly lower than those in group C (P<0.05).The levels of IL-6, IL-8 and MDA in group D at T(1)-T(5) were significantly lower than those in group C(P<0.05). The levels of IL-10 and SOD in group D at T(1)-T(5) were significantly higher than those in group C (P<0.05). The values of IQA, AI, and the expression of CHOP mRNA and their protein in the two groups at T(4) were significantly higher than those at T(2) (P<0.05). The values of IQA, AI, and the expression of CHOP mRNA and their protein in group D at T(4) were significantly lower than those in group C (P<0.05). Conclusions: Dexmedetomidine could attenuate the extent of lung injury in elderly patients with lung cancer undergoing thoracoscopic lobectomy. The pulmonary protective mechanism could be related to the inhibition of inflammatory factors in dexmedetomidine, improving oxidative stress and reducing Chop-mediated apoptosis of lung tissue by the protein.

[The mechanism of HOTAIR regulating the proliferation and apoptosis of prostate cancer cells by targeting down-regulation of miR-152 to improve the expression of FOXR2].

Objective: To clarify the effect of FOXR2 on the proliferation and apoptosis of prostate cancer cells and to reveal the mechanism. Methods: The expression of FOXR2 in clinical samples of prostate cancer were detected by Quantitative Real-time PCR (qRT-PCR) and Western blotting. The CCK8 proliferation kit and the Annexin V-FITC apoptosis kit, flow cytometry were used to detect the proliferation and apoptosis of prostate cancer cells with or without the FOXR2 knockdown. Combined with the results of microRNA chip, we predicted the related miR-152 and detected the relationship between miR-152 and FOXR2 by luciferase reporter gene assay. The correlation between HOTAIR and miR-152 is clearly defined by software prediction and qRT-PCR. Results: FOXR2 had a relatively high expression in the prostate cancer tissue.The mRNA expression of FOXR2 is 4.9 times that of adjacent tissues, and the protein level was also significantly up-regulated. In the PC3 cell line, the specific knock-down of FOXR2 inhibits the proliferation of cells and promotes cell apoptosis. According to the microRNA chip results and luciferase reporter gene assay, we found miR-152 could regulate the expression of FOXR2; and FOXR2 3 'UTR had two miR-152 binding sites, all of which could control the expression of FOXR2. The results of LNCediting and qRT-PCR suggest that HOTAIR is negatively correlated with the expression of miR-152, and is involved in the regulation of miR-152 expression in prostate cancer. Conclusion: FOXR2 up-regulation can promote the proliferation and inhibit the apoptosis of prostate cancer cells because that HOTAIR restrains the expression of miR-152.

Abdominal pain as a result of intermittent hydronephrosis.

OBJECTIVE: We report a minority of cases presented with abdominal pain due to intermittent hydronephrosis, to improve the recognition of this condition. PATIENTS AND METHODS: We retrospectively studied 1152 children complained of abdominal pain in our center from January 2010 to December 2015. Also, we analyzed the clinical presentation, treatment experience, examination results, and image features in detail. RESULTS: 14 patients received a diagnosis of intermittent hydronephrosis including 11 boys and 3 girls. 9 patients were affected on the left kidney and other 5 on the right side. All children presented recurrent abdominal pain, and the ultrasound images varied during different stages. All patients had been misdiagnosed and delayed treatment. CONCLUSIONS: Abdominal pain caused by intermittent hydronephrosis is easily misdiagnosed; all preschool children with a history of recurrent abdominal pain should be suspected of this condition.

[Advances in the research of three-dimensional skin printing].

As a new technology, three-dimensional printing possesses the characteristics of high precision and strong controllability, which has become a new technology and can be used in tissue engineering. Currently, using three-dimensional printing to build artificial skin has made certain achievement, and experiments in vitro have confirmed that the three-dimensional printing has the possibilities to build artificial skin whose structure and function are close to those of nature skin. However, the technology is not yet very mature and there are still some problems need to be solved, such as the recreation of the cutaneous appendages and the degradation and absorption of the extracellular matrix.

[The role of autophagy in the invasion and metastasis of the squamous cell carcinoma of head and neck].

Objective:The aim of this study is to explore the effects of autophagy on the metastasis of the Squamous Cell Carcinoma of Head and Neck (SCCHN) via epithelial to mesenchymal transition (EMT) induced by TGF-ß1. Method:Establish the EMT model induced by TGF-ß1 in the SCCHN in time/concentration, and the expression of autophagy related protein microtubule associated protein 1 light chain3 (LC3) detected by western blot; Autophagy inhibitor chloroquine (CQ), depressing autophagy, the expression of E-cadherin, cytokeratin, Vimentin and LC3 were examined by Western blot. Wound healing and Transwell invasion assay indicate the effects to metastasis for SCCHN. Result:Autophagy was activated within TGF-ß1 induced EMT model in the SCCHN in time/concentration dependently. After autophagy was suppressed, the expression of E-cadherin and cytokeratin increased while vimentin and the capacity of metastasis was reduced compared with control group. Conclusion:TGF-ß1 induce EMT and Autophagy in the SCCHN. Autophagy could enhances metastasis in the SCCHN via EMT induced by TGF-ß1.

[The correlation between cerebral MRI characteristics of posterior reversible encephalopathy syndrome and serum levels of PlGF, sEng in patients with pre-eclampsia].

Objective: To investigate the MRI characteristics of posterior reversible encephalopathy syndrome (PRES) in patients with pre-eclampsia(PE) and its correlation with serum placental growth factor (PlGF), soluble endoglin (sEng) and sEng/PlGF ratio. Methods: 34 patients with PE who were admitted to Guangdong Women and Children Hospital from September 2013 to March 2014 were studied retrospectively.13 cases had PRES and 21 cases had normal cerebral MRI. All patients underwent conventional MRI and DWI scanning. The score of brain edema (SBE) were calculated. PlGF, sEng concentrations were measured with ELISA. The levels of PlGF, sEng and sEng/PlGF were compared between the PRES group and the normal MRI groups. The correlation of sEng/PIGF ratio and SBE were studied as well. Results: The PlGF in the PRSE group was (231.4±66.8) ng/L, and in normal cerebral MRI group was (333.6±37.5) ng/L (t= 5.61, P<0.05). The sEng in the PRSE group was (5 256.2±879.6) ng/L, in normal cerebral MRI group was (3 955.6±537.7) ng/L (t=6.53, P<0.01).The sEng/PlGF in the PRSE group was (26.0±10.0) , and in normal cerebral MRI group was (11.9±1.6; t=8.41, P<0.01) , with the cut-off value of 20.0. The sensitivity was 81.8% and the specificity was 85.0%.There was no statistically significant correlation between PlGF, sEng and SBE (P>0.05).There was a positive correlation between the sEng/PlGF ratio and SBE (P>0.05). Conclusion: The value of sEng/PlGF ratio was correlated with brain edema score in PE. The serum sEng/PlGF ratio may be used as a reference for prediction of PRES.

[Advances in the research of application of collagen in three-dimensional bioprinting].

As a new industrial technology with characteristics of high precision and accuracy, the application of three-dimensional bioprinting technology is increasingly wide in the field of medical research. Collagen is one of the most common ingredients in tissue, and it has good biological material properties. There are many reports of using collagen as main composition of " ink" of three-dimensional bioprinting technology. However, the applied collagen is mainly from heterogeneous sources, which may cause some problems in application. Recombinant human source collagen can be obtained from microorganism fermentation by transgenic technology, but more research should be done to confirm its property. This article reviews the advances in the research of collagen and its biological application in three-dimensional bioprinting.

[Efficacy of a hydrosurgery system applied in the debridement of extensive residual wounds of patients with severe burn].

OBJECTIVE: To explore the efficacy of a hydrosurgery system applied in the debridement of extensive residual wounds of patients with severe burn prospectively. METHODS: Seventy-six severely burned patients with extensive residual wounds after treatment were admitted into Department of Burn Surgery of Changhai Hospital of the Second Military Medical University from May 2012 to November 2015. The patients were divided into hydrosurgery system debridement group (HD, n=34) and traditional debridement group (TD, n=42) according to the random number table, and their residual wounds were debrided by a hydrosurgery system and conventional surgical instruments respectively. The wounds of patients in two groups were repaired with stamp-like grafts made from split-thickness autoskin after debridement. Second time of debridement and skin grafting as above was performed if necessary. The time used in debriding 1% TBSA wound in the first surgery, positive rate of bacterial culture of wound exudate on post first surgery day (PFSD) 3, survival rate of skin grafts on PFSD 7, second debridement rate, and wound healing time of patients in two groups were compared. Data were processed with two independent-sample t test and chi-square test. RESULTS: The time used in debriding 1% TBSA wound of patients in the first surgery in group HD was (1.2±0.3) min, which was significantly shorter than that in group TD[(1.9±0.4) min, t=-9.098, P<0.001]. On PFSD 3, positive rate of bacterial culture of wound exudate of patients in group HD was 11.76% (4/34), which was significantly lower than that in group TD[38.10% (16/42), χ(2)=6.718, P=0.010]. On PFSD 7, the survival rate of skin grafts of patients in group HD was (90±8)%, which was significantly higher than that in group TD[(83±15)%, t=2.334, P=0.022]. The second debridement rate of patients in group HD was 5.88% (2/34), which was significantly lower than that in group TD[23.81% (10/42), χ(2)=4.542, P=0.033]. The wound healing time of patients in group HD was (10.6±1.5) d, which was significantly shorter than that in group TD[(13.3±2.5) d, t=-5.442, P<0.001]. CONCLUSIONS: The hydrosurgery system applied in the debridement of extensive residual wounds of patients with severe burn is thorough and highly efficient, which is beneficial to improving the survival rate of skin grafts and accelerating wound healing.

Comparative pathogenicity of Coxsackievirus A16 circulating and noncirculating strains in vitro and in a neonatal mouse model

An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain.

Comparative pathogenicity of Coxsackievirus A16 circulating and noncirculating strains in vitro and in a neonatal mouse model.

An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain.

Widespread white matter alterations in patients with end-stage renal disease: a voxelwise diffusion tensor imaging study.

BACKGROUND AND PURPOSE: ESRD results in excessive accumulation of urea and toxic metabolites. Hemodialysis is usually performed to maintain health in patients with ESRD; however, it may cause silent white matter alterations in the earlier stages. Hence, this study aimed to perform voxelwise diffusion tensor analysis for global detection of subtle white matter alterations in patients with ESRD. MATERIALS AND METHODS: Twenty-eight patients with ESRD and 25 age-matched control subjects were enrolled in this study. Each subject underwent CASI assessment and DTI. After spatial normalization of DTI images, voxelwise statistical analyses were performed to compare DTI parameters between the 2 groups. RESULTS: In patients with ESRD, AD, RD, and MD values were significantly increased, whereas the FA value was significantly decreased, mostly in the corpus callosum, bilateral sagittal stratum, and pons. Multiple regression analysis further revealed that both RD and MD were positively correlated with the duration of hemodialysis in the pons; however, no significant correlation was observed with FA. Negative correlations of RD and MD and a positive correlation of FA with the CASI score were observed in the corona radiata. CONCLUSIONS: We concluded that voxelwise DTI analysis is helpful in the detection of white matter alterations caused by hemodialysis.

NADPH oxidase inhibition prevents beta cell dysfunction induced by prolonged elevation of oleate in rodents.

AIMS/HYPOTHESIS: The activation of NADPH oxidase has been implicated in NEFA-induced beta cell dysfunction. However, the causal role of this activation in vivo remains unclear. Here, using rodents, we investigated whether pharmacological or genetic inhibition of NADPH oxidase could prevent NEFA-induced beta cell dysfunction in vivo. METHODS: Normal rats were infused for 48 h with saline or oleate with or without the NADPH oxidase inhibitor apocynin. In addition, NADPH oxidase subunit p47(phox)-null mice and wild-type littermate controls were infused with saline or oleate for 48 h. This was followed by measurement of NADPH oxidase activity, reactive oxygen species (ROS) and superoxide imaging and assessment of beta cell function in isolated islets and hyperglycaemic clamps. RESULTS: Oleate infusion in rats increased NADPH oxidase activity, consistent with increased total but not mitochondrial superoxide in islets and impaired beta cell function in isolated islets and during hyperglycaemic clamps. Co-infusion of apocynin with oleate normalised NADPH oxidase activity and total superoxide levels and prevented beta cell dysfunction. Similarly, 48 h NEFA elevation in wild-type mice increased total but not mitochondrial superoxide and impaired beta cell function in isolated islets. p47(phox)-null mice were protected against these effects when subjected to 48 h oleate infusion. Finally, oleate increased the levels of total ROS, in both models, whereas inhibition of NADPH oxidase prevented this increase, suggesting that NADPH oxidase is the main source of ROS in this model. CONCLUSIONS/INTERPRETATION: These data show that NADPH-oxidase-derived cytosolic superoxide is increased in islets upon oleate infusion in vivo; and whole-body NADPH-oxidase inhibition decreases superoxide in concert with restoration of islet function.

The use of pseudo-dynamic magnetic resonance imaging for evaluating the relationship between temporomandibular joint anterior disc displacement and joint pain.

The relationship between temporomandibular joint (TMJ) pain and the magnetic resonance imaging (MRI) finding of articular disc displacement is debated. The purpose of this study is to investigate the correlation between TMJ pain and anterior disc displacement (ADD) using pseudo-dynamic MRI. A retrospective review of MRI studies was carried out on 130 TMJs in 65 patients presenting unilateral TMJ pain. The contralateral asymptomatic joints served as the control group. Bilateral oblique sagittal and coronal MRIs as well as pseudo-dynamic studies in the oblique sagittal plane were obtained. The disc-condyle relationship was divided into three subtypes (normal disc position, ADD with reduction, and ADD without reduction), based on the pseudo-dynamic MRI findings. Fisher's exact test was used to determine whether the TMJ pain was linked to ADD. The results showed that TMJ pain was significantly related to ADD (with and without reduction) compared to the group with a normal disc position (P=.0001). A significant correlation was found between TMJ pain and the ADD subtype without reduction, as compared to the ADD subtype with reduction (P=.0156). These data suggest that a displaced disc, particularly in the subtype without reduction, is an important source of pain.

Deletion of p47phox attenuates the progression of diabetic nephropathy and reduces the severity of diabetes in the Akita mouse.

AIMS/HYPOTHESIS: Reactive oxygen species (ROS) contribute to diabetes-induced glomerular injury and endoplasmic reticulum (ER) stress-induced beta cell dysfunction, but the source of ROS has not been fully elucidated. Our aim was to determine whether p47(phox)-dependent activation of NADPH oxidase is responsible for hyperglycaemia-induced glomerular injury in the Akita mouse, a model of type 1 diabetes mellitus resulting from ER stress-induced beta cell dysfunction. METHODS: We examined the effect of deleting p47 (phox) (also known as Ncf1), the gene for the NADPH oxidase subunit, on diabetic nephropathy in the Akita mouse (Ins2 (WT/C96Y)) by studying four groups of mice: (1) non-diabetic mice (Ins2 (WT/WT)/p47 (phox+/+)); (2) non-diabetic p47 (phox)-null mice (Ins2 (WT/WT)/p47 (phox-/-)); (3) diabetic mice: (Ins2 (WT/C96Y)/p47 (phox+/+)); and (4) diabetic p47 (phox)-null mice (Ins2 (WT/C96Y)/p47 (phox-/-)). We measured the urinary albumin excretion rate, oxidative stress, mesangial matrix expansion, and plasma and pancreatic insulin concentrations in 16-week-old mice; we also measured glucose tolerance and insulin sensitivity, islet and glomerular NADPH oxidase activity and subunit expression, and pro-fibrotic gene expression in 8-week-old mice. In addition, we measured NADPH oxidase activity, subunit expression and pro-fibrotic gene expression in high glucose-treated murine mesangial cells. RESULTS: Deletion of p47 (phox) reduced kidney hypertrophy, oxidative stress and mesangial matrix expansion, and also reduced hyperglycaemia by increasing pancreatic and circulating insulin concentrations. p47 (phox-/-) mice exhibited improved glucose tolerance, but modestly decreased insulin sensitivity. Deletion of p47 (phox) attenuated high glucose-induced activation of NADPH oxidase and pro-fibrotic gene expression in glomeruli and mesangial cells. CONCLUSIONS/INTERPRETATION: Deletion of p47 (phox) attenuates diabetes-induced glomerular injury and beta cell dysfunction in the Akita mouse.

Ante-partum and post-partum markers of metabolic syndrome in pre-eclampsia.

It is rare for a study to address immediate metabolic change in pre-eclamptic pregnancy. Our aim is to study the ante-partum and post-partum metabolic markers in pre-eclampsia. A total of 33 pre-eclamptic and 200 uncomplicated women with singleton pregnancies were recruited for the prospective research. Immediately ante-partum and 24-48 h postpartum venous blood samples were collected for the analysis of metabolic markers. In the pre-eclamptic group, the ante-partum fasting glucose, fasting insulin, triglyceride and free fatty acid levels were found to be higher than in the control group; however, ante-partum high-density lipoprotein level was lower. Interestingly, fasting glucose and insulin levels decreased by 24-48 h post-partum in both groups and no significant differences were found. Pre-eclamptic patients had lower post-partum high-density lipoprotein (P=0.02), higher triglyceride (P<0.001), higher free fatty acid (P=0.02) and higher apolipoprotein B levels (P=0.01) than the control group. Dyslipidemia lasts from ante-partum to immediate post-partum in pre-eclamptic women in the form of increased triglyceride, higher free fatty acid and decreased high-density lipoprotein levels. We speculate that women with dyslipidemia and higher baseline blood pressure tend to develop pre-eclampsia during pregnancy. Hence, the development of pre-eclampsia may be a 'marker' of possible future cardiovascular or metabolic disease.

Prediction of conversion from clinically isolated syndrome to clinically definite multiple sclerosis according to baseline MRI findings: comparison of revised McDonald criteria and Swanton modified criteria.

BACKGROUND: The International Panel on the Diagnosis of Multiple Sclerosis first incorporated abnormalities demonstrated by brain and spinal cord MRI into the diagnostic criteria (McDonald criteria) for multiple sclerosis (MS), which were later revised in 2005. In 2006, Swanton and colleagues modified the MRI criteria to simplify and speed the diagnosis. OBJECTIVE: The purpose of this study was to compare the ability of two sets of criteria (the revised McDonald MRI criteria and Swanton's modified criteria) to predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) from baseline MRI findings. METHODS: Sixty-four patients presenting with CIS suggestive of multiple sclerosis were recruited from 2001 to 2006 and followed up for at least 2 years. Their baseline brain and spinal cord MRI studies were retrospectively evaluated. The patients who developed CDMS during follow-up were treated as positive cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the two MRI dissemination-in-space criteria were calculated. RESULTS: Thirty patients (46.9%) converted to CDMS. The sensitivity specificity, PPV, NPV and accuracy (%) of the revised McDonald criteria were 53, 100, 100, 71 and 78, respectively, while those for Swanton's modified criteria were 60, 100, 100, 74 and 81. CONCLUSIONS: In conclusion, Swanton's modified criteria are more sensitive and accurate (but not significantly so). However, Swanton's criteria are simpler to use and have equally high specificity and PPV.