[Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus].

Objectives: Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE. Methods: The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE. Results: Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease (HR=6.360), positive anti-double-stranded DNA antibodies (HR=7.203), low level of complement C3 (HR=25.715), and low level of complement C4 (HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events (HR=0.109) were protective factors (P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS (HR=0.753, 95%CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions: PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.

[Establishment method and significance of birthweight curve and reference in single center].

Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.

Use of CT-based renal volumetry for the measurement of split renal function: a split glomerular filtration rate prediction model based on unilateral renal volume parameters.

AIM: To develop a split glomerular filtration rate (sGFR) prediction model based on unilateral renal volume parameters using three-dimensional (3D) computed tomography (CT) volumetry. MATERIALS AND METHODS: Clinical data (age, sex, height, weight, serum creatinine level [sCr], and sGFR measured by 99mTc-diethylene triamine pentaacetic acid nuclear renal scintigraphy with the double plasma sample method) of 67 healthy renal donors and 111 patients with hydronephrosis admitted from April 2016 to September 2021 were analysed. The split renal parenchymal volume (sRPV) and split renal calyces and pelvis volume (sRCPV) of 67 unilateral donor left kidneys and 111 hydronephrotic kidneys were measured. Statistical analysis of these parameters was performed to develop and validate the sGFR prediction model. RESULTS: sRPV (p<0.001), sRCPV (p=0.012), age (p=0.015), serum creatinine level (p=0.004), and weight (p=0.006) were significantly associated with the measured sGFR and were included in the sGFR prediction formula, which was constructed as: 68.710 + 0.093 × sRPV-0.041 × sRCPV-0.228 × W-0.219 × A-14.432 × sCr (r2 = 0.416; where A is age, W is weight). The paired difference of internal validation between the measured sGFR (42.34 ± 13.71 ml/min/1.73 m2) and the sGFR estimated by the prediction model (41.46 ± 8.99 ml/min/1.73 m2) was 0.879 ± 11.475 ml/min/1.73 m2 (p=0.492) with a 95% confidence interval of the mean difference of ±2.54 ml/min/1.73 m2. CONCLUSION: The proposed model based on sRPV and sRCPV parameters could be used for estimating split renal function of healthy renal donors and patients with hydronephrosis to some extent. Further studies are required to evaluate and rectify the model.

[Association between gestational blood pressure and pregnancy induced hypertension or pre-eclampsia].

Objective: To construct the gestational-age-specific blood pressure curve and percentile blood pressure values of pregnant women in Jiangsu Province, and to explore the clinic significance of the blood pressure changes in women whose blood pressure was less than 140/90 mmHg (1 mmHg=0.133 kPa) in each trimester and eventually developed pregnancy induced hypertension (PIH) or pre-eclampsia (PE). Methods: A prospective longitudinal cohort during pregnancy was built. Singleton pregnant women in the first trimester (11-13+6 weeks) were recruited from July 2017 to September 2020 in Nanjing Drum Tower Hospital, and were followed up in the second trimester (19-23+6 weeks), the third trimester (30-33+6 weeks) and approaching the expected date of delivery (35-38+6 weeks). The Viewpoint 6.0 software was used to record pregnancy-related information. The blood pressure was measured by standard methods in our clinic. Least mean square (LMS) function was performed to fit the gestational-age-specific blood pressure curve and percentile blood pressure values were calculated at every follow-up time point. Logistic regression was applied to calculate the OR for the groups with blood pressure ≥95th percentile (P95). Results: There were 3 728 singleton pregnant women invited in this study, including 3 490 normal pregnant women (93.62%, 3 490/3 728), and 238 pregnant women with PIH or PE (6.38%, 238/3 728). Gestational-age-specific blood pressure curve showed that systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) decreased in the second trimester, compared with those in the first and the third trimester, however the fluctuation of blood pressure was low, but regardless of the gestational age, P95 of SBP, DBP and MAP increased by 14, 11 and 11 mmHg respectively, compared with 50th percentile (P50). In the first trimester, the risk of developing PIH or PE finally in pregnant women with blood pressure ≥P95 was 4.36-fold (95%CI: 2.99-6.35) for SBP than women with SBP

Cine magnetic resonance urography for postoperative evaluation of reconstructive urinary tract after ileal ureter substitution: initial experience.

AIM: To report the initial experiences with functional cine magnetic resonance urography (cine MRU) and assess its usefulness as a novel postoperative evaluation method of ileal ureter substitution. MATERIALS AND METHODS: The medical records of 17 patients from who underwent cine MRU during June 2010 to December 2019 during their follow-up after ileal ureter substitution were collected. The cine MRU videos of reconstructive urinary tract were observed, and the luminal diameter, contraction ratio, peristaltic waves, and ureteral jets were measured. RESULTS: Seventeen patients underwent cine MRU after ileal ureter substitution during their follow-up. Based on their cine MRU videos assessing the morphology and the peristaltic motility of the reconstructive urinary tract, there was resolution of preoperative hydronephrosis, which matched their ameliorative renal function. Clearly, peristaltic motility of the ileal graft was observed in 14 patients with obvious peristaltic waves and ureteral jets. CONCLUSION: This study is the first to assess the clinical utility of functional cine MRU during the patient follow-up after ileal ureter substitution. Cine MRU is a radiation-free, non-invasive imaging method that can clearly show the morphology and the peristaltic motility of the ileal graft. Therefore, cine MRU, as a novel technique, will be extremely useful in the postoperative evaluation of patients after ileal ureter substitution.

[Application of preoperative three-dimensional image reconstruction in the treatment of ureteropelvic junction obstruction].

OBJECTIVE: To investigate the value of preoperative three-dimensional image reconstruction in the treatment of ureteropelvic junction obstruction (UPJO). METHODS: We reviewed data on 40 patients (22 male cases, and 18 female cases) diagnosed with UPJO in Peking University First Hospital from May 2017 to April 2019. The median age was 26.5 years (IQR 23.25-38.75) years. There were 11 patients complicated with ectopic vessels, 14 patients with kidney stones, 3 patients with horseshoe kidney, and 6 patients with obstruction after pyeloplasty. All the patients underwent preoperative enhanced CT scan, and the CT data were reconstructed into three-dimensional image models. The obstruction position of ureteropelvic junction and the relationship between ureteropelvic junction and blood vessels and organs were observed by three-dimensional models to assist planning surgery. Thirty-seven patients underwent laparoscopic pyeloplasty (including 3 cases combined with pyelolithotomy with flexible cystoscope, 1 case combined with pyelolithotomy by sun-style cystoscope, 1 case with laparoscopic ureter resection and anastomosis, 3 cases of laparoscopic pyeloplasty of horseshoe kidney), 2 patients underwent laparoscopic ventral onlay lingual mucosal graft ureteroplasty, and 1 patient underwent robot-assisted laparoscopic pyeloplasty. RESULTS: Three-dimensional CT image clearly showed the relationship between the obstruction of ureteropelvic junction and blood vessels and organs after three-dimensional reconstruction. The type, diameter, position and direction of the ectopic vessels could be observed clearly before operation according to the three-dimensional reconstruction model, and the number, size, location and shape of renal calculi or other masses, the number of involved renal calyces and the anatomical distribution in the renal pelvis and calyces could be also evaluated preoperatively. After comprehensive analysis of the above information, individualized operation plans were performed on the patients, all the 40 cases were successfully completed with the surgery without any transfer to open surgery. The average operative time was (129.91±37.90) min (range: 75 to 273), the average blood loss was (48.1±78.0) mL (range: 10 to 400), the average hospitality was (5.04±1.99) d (range: 2 to 10), and the average postoperative drainage time was (3.8±1.4) d (range: 2 to 8). CONCLUSION: The preoperative three-dimensional image reconstruction has a high clinical value in the treatment of ureteropelvic junction obstruction, and it is of great help to assist surgery planning and is worthy of further clinical promotion and application.

[Prospective cohort study of fetal nuchal translucency in first-trimester and pregnancy outcome].

Objective: To explore the relationship between fetal nuchal translucency (NT) in the first trimester and pregnancy outcome. Methods: A prospective cohort study was conducted in Nanjjing Drum Tower Hospital from December 2015 to December 2018, 4 958 singleton pregnant women were enrolled to screen fetal ultrasound structure and serology in the first trimester, ultrasound in the second trimester and neonatus physical examination 28 days after birth. According to the results of NT, 167 cases of fetus with increased NT (≥3.0 mm) and 4 791 cases of normal NT were divided, moreover, 86 cases with isolate increased NT and 81 cases of increased NT combined with structural abnormality. The prognosis of fetuses with different NT thickness was analyzed, and the pregnancy outcome of fetuses with isolate increased NT or combined with structural abnormality were analyzed. In the first trimester, if the fetal structure was abnormal or the serological screening result was high risk, the chromosomal microarray analysis (CMA) would be performed by chorionic villus sampling to determine the prenatal diagnosis. Results: (1) The pregnancy outcome for fetus of normal NT: there were 4 791 cases with normal NT. Totally, 4 726 cases with normal NT and no structural abnormalities were screened out in the firsttrimester. In this group, 5 cases of aneuploidies were diagnosed based on high risk of maternal serum biomarkers and 83 cases of structural abnormalities were screened out in the subsequent ultrasound scan and the neonatal examination. Another 65 cases with normal NT present complicated with structural anomalies were screened out in the first trimester and 4 cases were diagnosed as aneuploidies. (2) The pregnancy outcome for fetus of isolate increased NT: 66 (76.7%, 66/86) cases of isolated increased NT were performed CMA, 3 cases were diagnosed as trisomy 21 and terminated pregnancy. Another 4 cases were terminated pregnancy privately without cytogenetic diagnosis. No further anomalies were found in 79 cases till 6 to 21 months postnatally. (3) The pregnancy outcome for fetus of increased NT with structural anomalies: increased NT present with structural anomalies were screened out by detailed anomaly scan in the first trimester and 32 of them were confirmed as aneuploidies. In this group, 70 cases terminated pregnancy, 2 cases had spontaneous miscarriages and 9 cases had liveborns (1 newborn was found ventricular septal defect). (4) The pregnancy outcome for fetus of increased NT with or without structural anomalies: the percentage of aneuploidies in fetuses with isolated increased NT (3.5%, 3/86) was significantly lower than those with structural abnormalities (39.5%,32/81). The healthy survival rate in fetuses with isolated increased NT (91.9%,79/86) was significantly higher than those with structural abnormalities (9.9%, 8/81). Conclusions: A detailed first-trimester anomaly scan could improve prenatal screening efficiency of birth defects. Compared to the fetuses with increased NT combined with structural abnormalities, the healthy survival rate of fetuses with isolated increased NT based on detailed first-trimester anomaly scan is higher and the percentage of fetal aneuploidies is lower.

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy.

Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. Results: A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. Conclusion: CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.

Rigid and remodelled: cerebrovascular structure and function after experimental high-thoracic spinal cord transection.

High-thoracic or cervical spinal cord injury (SCI) is associated with several critical clinical conditions related to impaired cerebrovascular health, including: 300-400% increased risk of stroke, cognitive decline and diminished cerebral blood flow regulation. The purpose of this study was to examine the influence of high-thoracic (T3 spinal segment) SCI on cerebrovascular structure and function, as well as molecular markers of profibrosis. Seven weeks after complete T3 spinal cord transection (T3-SCI, n = 15) or sham injury (Sham, n = 10), rats were sacrificed for either middle cerebral artery (MCA) structure and function assessments via ex vivo pressure myography, or immunohistochemical analyses. Myogenic tone was unchanged, but over a range of transmural pressures, inward remodelling occurred after T3-SCI with a 40% reduction in distensibility (both P < 0.05), and a 33% reduction in vasoconstrictive reactivity to 5-HT trending toward significance (P = 0.09). After T3-SCI, the MCA had more collagen I (42%), collagen III (24%), transforming growth factor ß (47%) and angiotensin II receptor type 2 (132%), 27% less elastin as well as concurrent increased wall thickness and reduced lumen diameter (all P < 0.05). Sympathetic innervation (tyrosine hydroxylase-positive axon density) and endothelium-dependent dilatation (carbachol) of the MCA were not different between groups. This study demonstrates profibrosis and hypertrophic inward remodelling within the largest cerebral artery after high-thoracic SCI, leading to increased stiffness and possibly impaired reactivity. These deleterious adaptations would substantially undermine the capacity for regulation of cerebral blood flow and probably underlie several cerebrovascular clinical conditions in the SCI population.

[Blood cerebrospinal fluid barrier damage of rats induced by lead acetate or nano-lead exposure].

OBJECTIVE: To investigate the damage of blood-cerebrospinal fluid barrier (BCB) of rats induced by lead and nano-lead exposure in order to provide the basis for mechanism study of lead neurotoxicity. METHODS: 39 male rats were randomly divided into control group, lead acetate exposed group and nano-lead exposed group. Rats in lead acetate exposed group and nano-lead exposed group were given 20 mg/kg lead acetate or nano-lead by oral gavage and rats in control groups were given the same amount saline for 9 weeks.Morris maze was used to test the learning function, serum albumin and CSF albumin were determined by ELISA. Confocal laser scanning microscope was applied to detect ZO-1 and Occludin protein expression in choroid plexus, real time-PCR was used to test the expression of ZO-1 and Occludin mRNA expression. Pathological changes of choroid plexus cells were observed by the electron microscopy. RESULTS: Compared with the control group, the escape latency of rats in lead acetate or nano-lead exposure group were longer and times of across platform were less. The levels of CSF albumin and the CSF albumin index in lead acetate or nano-lead exposed rats were obviously higher, and the fluorescence intensity of ZO-1, Occludin as well as mRNA expressions were lower than those in control group(P<0.05). Compared with lead acetate exposed group, the levels of CSF albumin and the CSF albumin index in nano-lead exposure group were higher. The fluorescence intensity and mRNA expressions of ZO-1, Occludin in nano-lead exposure group were than those in lead acetate group(P<0.05). Electron microscopy revealed that lead acetate or nano-lead exposure could induce shorter microvillus of choroid plexus epithelial cells, mitochondrion destruction and partial disconnection in intracellular junctions between two adjacent epithelial cells. CONCLUSION: Lead acetate and nano-lead exposed can result in the blood-cerebrospinal fluid barrier damage, which may involve in the process of lead induced neurotoxicity. Meanwhile, nano-lead exposure can induced in more worse damage in terms of blood-results in blood-cerebrospinal fluid barrier function.

Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 alpha activation.

The goal of this study was to explore the molecular mechanism of hypoxia inducible factor-1 alpha (HIF-1 alpha) action on migration and invasion of esophageal carcinoma cells. We used cobalt chloride (CoCl(2) ) to mimic tumor hypoxic microenvironment and analyzed the expressions of E-cadherin, matrix metalloproteinase-2 (MMP-2), and HIF-1 alpha in esophageal carcinoma cells under hypoxia by reverse transcription polymerase chain reaction and Western blotting. To analyze the function of HIF-1 alpha in Eca109 and TE1 cells, we established stable HIF-1 alpha knockdown cells using small interfering RNA. Blocking effect was detected by Western blotting. The concentrations of MMP-2 protein in the conditioned medium were also determined by enzyme-linked immunosorbent assay. Wound-healing and cell invasion assay were used to evaluate the migration and invasion of esophageal carcinoma cells. After exposure to hypoxia, expressions of HIF-1 alpha protein in Eca109 and TE1 cells were upregulated, both mRNA and protein levels of E-cadherin were downregulated, and MMP-2 were upregulated (P < 0.05), whereas HIF-1 alpha mRNA had no significant change (P > 0.05). Small interfering RNA could block HIF-1 alpha effectively under hypoxia, then enhanced E-cadherin expression and inhibited MMP-2 expression, respectively. Furthermore, expression of HIF-1 alpha protein was stable even though MMP-2 repressed by BB2516. Compared with that in normoxia, Snail expression was enhanced when Eca109 or TE1 cells exposed to hypoxia. Once HIF-1 alpha blocked, Snail expressions were inhibited accordingly. Wound recovery and the number of invading cells decreased (P < 0.05) after HIF-1 alpha blocked. The hypoxia suppresses E-cadherin expression and enhances MMP-2 expression favoring esophageal carcinoma migration and invasion via HIF-1 alpha activation. Our observations suggest that HIF-1 alpha inhibition might be an effective strategy to weaken the migration and invasion of esophageal carcinoma cells.

Involvement of nNOS in the antinociceptive activity of melatonin in inflammatory pain at the level of sensory neurons.

OBJECTIVE: The efficacy of melatonin as an analgesic agent has been well documented in animals and humans. However, the underlying mechanisms by which melatonin exerts antinociceptive effects on inflammatory pain are poorly understood. Here, we investigated the potential of melatonin to ameliorate inflammatory pain. MATERIALS AND METHODS: In vitro, ND7/23 neurons were treated with capsaicin. We used PCR and Western blot analyses to detect the expression of neuronal nitric oxide synthase (nNOS) in response to melatonin. Orofacial inflammatory pain was induced by 4% formalin administration on the right whisker pad of Sprague Dawley (SD) rats. The analgesic effect of melatonin was evaluated using mechanical threshold analyses. The expression level of nNOS in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (Vc) neurons was assessed by RNAscope and immunohistochemistry. RESULTS: In vitro, capsaicin upregulated the expression of nNOS, which was dose-dependently reversed by melatonin pretreatment (p < 0.001). In a rat model of orofacial inflammatory pain, melatonin pretreatment significantly attenuated mechanical allodynia in both the acute and chronic phases (p < 0.05). Furthermore, melatonin decreased the formalin-evoked elevated nNOS mRNA and protein levels in the TG and Vc neurons in the acute and chronic phases (p < 0.05). CONCLUSIONS: Taken together, these results suggest that nNOS may play an active role in both peripheral and central processing of nociceptive information following orofacial inflammatory pain induction. The regulatory effect of melatonin on nNOS in inflammatory pain may have potential implications for the development of novel analgesic strategies.

Bionic dental pulp: its potential value following root canal therapy.

Dental pulp can provide nutrition for teeth. The teeth after root canal therapy without pulp will turn frailer because of dehydration, and it may be easily broken. Bionic dental pulp possesses similar components of the healthy dental pulp. So we put forward a hypothesis that bionic dental pulp can be filled into root canals to provide nutrition for teeth like healthy pulp. Then the life-span of teeth after root canal therapy could increase.

Melatonin regulates mitochondrial function and biogenesis during rat dental papilla cell differentiation.

OBJECTIVE: The aim of this study was to investigate the effect of melatonin on mitochondria of dental papilla cells (DPCs) during the odontogenic differentiation process. MATERIALS AND METHODS: Primary DPCs were obtained from the first molar dental papilla of neonatal rats and cultured in osteogenic (OS) or basal medium supplemented with melatonin at different concentrations (0, 1 pM, 0.1 nM, 10 nM, and 1 µM) for differentiation in vitro. Effects of melatonin on differentiation, mitochondrial respiratory function, and mitochondrial biogenesis of DPCs were analyzed. RESULTS: Upon odontogenic induction, Alkaline phosphatase (ALP) activity, dentin sialophosphoprotein (DSPP), and dentin matrix protein (DMP1) expression were significantly enhanced, with a peaked expression at 10 nM of melatonin treatment. During DPCs differentiation, 10 nM melatonin could significantly induce the increase of intracellular Adenosine triphosphate (ATP), the decrease of the oxidized form of nicotinamide adenine dinucleotide (NAD+)/NADH ratio and reactive oxygen species (ROS). The mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (TFAM) were significantly increased, and the peak level of expression was found in cells treated with 10 nM of melatonin. Furthermore, the mitochondria DNA (mtDNA) copy number was significantly decreased during DPCs differentiation. CONCLUSIONS: These findings suggest that melatonin can promote the differentiation of rat DPCs and regulate mitochondrial energy metabolism, ROS scavenging, and mitochondrial biogenesis.

A fusion-based clinical decision support for disease diagnosis from endoscopic images.

This paper presents an intelligent decision support system designed on a decision fusion framework coupled with a priori knowledge base for abnormality detection from endoscopic images. Sub-decisions are made based on associated component feature sets derived from the endoscopic images and predefined algorithms, and subsequently fused to classify the patient state. Bayesian probability computations are employed to evaluate the accuracies of sub-decisions, which are utilized in estimating the probability of the fused decision. The overall detectability of abnormalities by using the proposed fusion approach is improved in terms of detection of true positive and true negative conditions when compared with corresponding results from individual methods.

Bionic restorative system: its potential value in caries therapy.

Dental defect caused by dental caries is usually restored by fillings, inlays or onlays at the present day. Although the therapeutic effects of these methods have already been confirmed, complications occasionally set in, such as pulp injury, fracture and secondary caries. Bionic dental organic center possesses similar functions of the natural dental organic center. So we put forward a hypothesis that bionic organic center can be transplanted onto the conditioned pulpal walls of the prepared cavity and a specific filling material, which the cavity will be filled with, provides oxygen, nutrition and raw materials for it to regenerate the lost odontal tissue in vivo. The regenerated odontal tissue which has similar properties of the healthy odontal tissue will restore the defect and it will be combined with the residual odontal tissue tightly, not only in physical structure but also in function. Then the teeth suffering from dental caries could live and function like healthy ones.