[Clinical features and risk factors of metabolic syndrome in adult hypopituitary patients].

Objective: To investigate the clinical features and risk factors of metabolic syndrome (MS) in adult hypopituitary patients (HP). Methods: Patients diagnosed with HP in the outpatient or inpatient department of the endocrinology department in West China Hospital from January,2012 to December,2019 were selected as the experimental group (HP group), and patients with normal pituitary function treated for saddle lesions were selected as the control group. HP patients with or without MS were divided into MS group and non-MS group HP patients were divided into four groups according to the level of growth hormone by the quartile method (GH>0.35 µg/L、0.13 µg/L0.35 µg/L、0.13 µg/L

[Parotid CT imaging reporting and data system: A preliminary study].

OBJECTIVE: To establish a Parotid Imaging Reporting and Data System (PI-RADS) for CT diagnosis of the parotid gland neoplasms and to investigate the clinical applicable value and feasibility of PI-RADS. METHODS: Patients who had been diagnosed with primary parotid gland neoplasms and had received surgical treatments in Peking University School and Hospital of Stomatology during the period of January 2013 to December 2016 were included in this study. The diagnoses were confirmed by the postoperative pathological examinations in all the patients. The CT imaging data of all patients were retrospectively reviewed and analyzed by two readers in consensus. Imaging characteristics related to the parotid neoplasms were extracted and quantified. Based on comprehensive analysis of the imaging characteristics, the probabilities of the benign and malignant neoplasms were evaluated and classified into six grades, PI-RADS 1-6 (PI-RADS 1: normal parotid gland; PI-RADS 2: confidently benign lesions; PI-RADS 3: probably benign lesions without confirmed evidence of malignancy; PI-RADS 4: suspected malignancy without sufficient evidence of malignancy; PI-RADS 5: confidently malignant lesions; PI-RADS 6: lesions with confirmed pathological evidence of malignancy). RESULTS: A total of 897 patients with 1 003 parotid lesions were included. The lesions included 905 benign and 98 malignant lesions. The proportions of the malignancies in PI-RADS 2, PI-RADS 3, PI-RADS 4 and PI-RADS 5 according to the two readers in consensus were 0.4%, 5.7%, 35.5% and 96.7% respectively. The overall Cohen's Kappa test showed medium consistency between the two independent researchers (κ=0.614, P<0.001, 95%CI: 0.569-0.695). Pearson Chi-square test showed that the proportions of malignancies increased with the diagnostic PI-RADS grades (Cochran-Armitage trend test, Z=-15.579, P<0.001). The results of Pearson Chi-square tests showed significant differences between the grades [PI-RADS 2 and 3 (χ²=12.048, P=0.001); PI-RADS 3 and 4 (χ²=75.231, P<0.001); PI-RADS 4 and 5 (χ²=32.266, P<0.001)]. CONCLUSION: PI-RADS can be used to evaluate the risk of malignancy and will be helpful to improve the imaging diagnosis and clinical treatment of parotid gland neoplasms.

[BRAF gene mutations in ameloblastic fibromas].

OBJECTIVE: To investigate the BRAF gene mutations in ameloblastic fibroma (AF), and to further analyze the relationship between the BRAF mutation and clinical characteristics so as to provide new reference to the study of AF's molecular pathology. METHODS: Sixteen cases diagnosed as AF at the Department of Oral Pathology, Peking University School of Stomatology between January 1990 and December 2017 were collected. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues using the QIAamp DNA Mini Kit (Qiagen, Germany) according to the manufacturer's instructions. Polymerase chain reaction (PCR) and direct sequencings were used to detect the BRAF gene mutations. The clinicopathological data, such as the age, location of the lesion, symptoms and treatments were retrospectively analyzed. RESULTS: The sixteen cases of AF involved nine women and seven men aged 2-67 years. Three lesions occurred in the maxilla and thirteen in the mandible. The most common presenting symptom of AF was a painless slowly enlarging mass with swelling. Ten patients received conservative treatment and the other six patients received radical surgery. Three cases relapsed during the study period. BRAF gene mutation was found in sixteen of all the sixteen samples analyzed (100%). The BRAF mutation was a point mutation with a thymine-adenine transversion at nucleotide 1 799 of 15 exons, resulting in a change at residue 600 that substituted glutamine for valine. This mutation was the strongest activator of the downstream RAS/RAF/MEK/ERK-MAPK signaling pathway. This helped to bring about a gain-of-function mutation due to a V600E substitution. Many studies identified that BRAF regulated survival, apoptosis, and proliferation of cells by inducing MAPK pathways activation. For the existing cases, none of the age, sex, location, recurrence and treatments had a statistically significant correlation with BRAF mutation. CONCLUSION: Our findings demonstrated high prevalence of BRAF V600E mutation in AF. The pathogenic role remains to be clarified．.

Duration of general anaesthetic exposure in early childhood and long-term language and cognitive ability.

BACKGROUND: The anaesthetic dose causing neurotoxicity in animals has been evaluated, but the relationship between duration of volatile anaesthetic (VA) exposure and neurodevelopment in children remains unclear. METHODS: Data were obtained from the Western Australian Pregnancy Cohort (Raine) Study, with language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E] and Total [CELF-T]) and cognition (Coloured Progressive Matrices [CPM]) assessed at age 10 yr. Medical records were reviewed, and children divided into quartiles based on total VA exposure duration before age three yr. The association between test score and exposure duration quartile was evaluated using linear regression, adjusting for patient characteristics and comorbidity. RESULTS: Of 1622 children with available test scores, 148 had documented VA exposure and were split into the following quartiles: ≤25, >25 to ≤35, >35 to ≤60 and >60 min. Compared with unexposed children, CELF-T scores for children in the first and second quartiles did not differ, but those in the third and fourth quartiles had significantly lower scores ([3 rd quartile - Unexposed] -5.3; 95% confidence interval [CI], (-10.2 - -0.4), [4 th quartile - Unexposed] -6.2; 95% CI, (-11.6 - -0.9). CELF-E showed similar findings, but significant differences were not found in CELF-R or CPM for any quartile. CONCLUSIONS: Children with VA exposures ≤35 min did not differ from unexposed children, but those with exposures >35 min had lower total and expressive language scores. It remains unclear if this is a dose-response relationship, or if children requiring longer exposures for longer surgeries have other clinical reasons for lower scores.

Clinical features of tumours and tumour-like pathologies involving the buccal fat pad.

This study aimed to investigate the clinical, radiological, and pathological characteristics of pathologies involving the buccal fat pad (BFP) and to explore the treatment protocols. The cases of 109 patients with primary pathologies involving the BFP (pBFP) diagnosed between January 2013 and September 2021 were assessed. The patients' clinical presentations and radiological and histopathological findings were analysed retrospectively, and their treatment outcomes were evaluated. The 109 pBFP were categorized as benign tumours (n = 17), malignant tumours (n = 29), vascular malformations (n = 38), and inflammatory masses (n = 25). Of the 17 benign tumours, seven were lipomas, five were pleomorphic adenomas, three were solitary fibrous tumours, and two were other tumours. The 29 malignant tumours included five adenoid cystic carcinomas, six mucoepidermoid carcinomas, three synovial sarcomas, and 15 other tumours. Of the 38 vascular malformations, 37 were venous and one was arteriovenous. Regarding the inflammatory masses, the lesions appeared after cosmetic facial botulinum toxin injection in 13 cases and after other cosmetic facial procedures in five. The upper body of the BFP was the most frequently involved site (79/109), while other frequently involved sites were the lower body (67/109) and the masseteric (41/109), temporal (32/109), and pterygopalatine (30/109) extensions.

Natural course of severe temporomandibular joint osteoarthrosis evaluated by a novel condylar remodelling scoring system and quantitative volumetric analysis.

Temporomandibular joint osteoarthrosis (TMJ-OA) frequently causes mild, moderate, or severe condylar morphological changes. A novel condylar remodelling scoring system (CRSS) based on three-dimensional cone beam computed tomography images is proposed, which is used to grade condylar morphological changes. In the CRSS, the condyle is divided into 10 regions by 11 reference points. For each increase in the number of regions involved in TMJ-OA, one point is subtracted from the full score of 10. The intra-class correlation coefficients for intra- and inter-observer agreement (range 0.656-0.898 and 0.841-0.906, respectively) indicated that the CRSS had good reliability. Cephalometric analysis showed that the condyles with severe morphological changes were prone to present with a retrognathic and clockwise rotating mandible, shorter ramus height, reduced mandibular length, larger mandibular angle, and maxillary retrusion. Qualitative CRSS evaluation and quantitative volumetric analysis were performed to evaluate the stability of severe TMJ-OA in its natural course (343 condyles). The continuous cortex group showed no remarkable changes with an average follow-up of 2 years. In the discontinuous cortex group, most (74.4%) converted into a continuous cortex during follow-up (mean 2 years).

Citrullinated vimentin stimulates proliferation, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression of fibroblast-like synoviocytes in rheumatoid arthritis.

OBJECTIVES: We aimed to investigate the possible effects of vimentin (Vim) and citrullinated Vim (cVim) on proliferation capacity, pro-inflammatory cytokine secretion, and the expression of peptidylarginine deiminase type 4 (PADI4) and receptor activator of nuclear factor kappa B ligand (RANKL) in cultured fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. METHOD: Human native Vim was citrullinated with rabbit PAD in vitro and detected using a Western blot assay with anti-modified citrulline antibody (anti-MC Ab). FLSs from RA or OA synovial samples were stimulated with Vim or cVim. Cell proliferation capacity was determined using the Celltiter 96 AQueous cell proliferation assay. The concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The expression of PADI4 and RANKL was measured by real-time polymerase chain reaction (RT-PCR) and a Western blot assay. RESULTS: Our Western blot assay with anti-MC Ab indicated that the amount of cVim increased significantly after Vim had been incubated with rabbit PAD in vitro. The proliferation capacity and secretion of TNF-α and IL-1 were significantly enhanced in the FLSs of RA patients when treated with cVim. However, when treated with Vim, an inhibitory effect on the proliferation capacity was noted in the FLSs from RA and also from OA patients. cVim significantly increased the expression of PADI4 and RANKL in the FLSs from RA patients. CONCLUSION: cVim seems to have remarkable biological effects on RA as confirmed by the stimulation of proliferation capacity, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression in the FLSs of RA patients.

A functional haplotype and expression of the PADI4 gene associated with increased rheumatoid arthritis susceptibility in Chinese.

To evaluate the association of single-nucleotide polymorphisms (SNPs) in PADI4 mRNA with rheumatoid arthritis (RA) in a Chinese population, we examined the distribution of four exonic SNPs of the PADI4 gene (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C and padi4_104*T/C) and PADI4 gene expression in 70 RA patients and 81 controls. Increased RA susceptibility was associated with the minor alleles of padi4_89 (P = 0.012), padi4_90 (P = 0.002), padi4_104 (P = 0.001) and the functional haplotype carrying the four minor alleles (P = 0.008). Human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles were also associated with increased RA susceptibility, and the individuals with minor alleles of four exonic SNPs and SE alleles showed more increased RA susceptibility. The PADI4 expression was significantly higher in RA patients than in controls (P < 0.001). HLA-DRB1 SE alleles and the genotypes carrying the minor alleles of four SNPs were associated with increased PADI4 expression. It is concluded that PADI4 SNPs, functional haplotype and PADI4 expression may contribute to an inherited predisposition to RA in a Chinese population.

PTCH1 and SMO gene alterations in keratocystic odontogenic tumors.

UNLABELLED: Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive jaw lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations in the PTCH1 (PTCH) gene are responsible for NBCCS and are related in tumors associated with this syndrome. Mutations in the SMO gene have been identified in basal cell carcinoma and in medulloblastoma, both of which are features of NBCCS. To clarify the role of PTCH1 and SMO in KCOTs, we undertook mutational analysis of PTCH1 and SMO in 20 sporadic and 10 NBCCS-associated KCOTs, and for SMO, 20 additional cases of KCOTs with known PTCH1 status were also included. Eleven novel (1 of which occurred twice) and 5 known PTCH1 mutations were identified. However, no pathogenic mutation was detected in SMO. Our findings suggest that mutations are rare in SMO, but frequent in PTCH1 in sporadic and NBCCS-associated KCOTs. ABBREVIATIONS: NBCCS, nevoid basal cell carcinoma syndrome; KCOTs, keratocystic odontogenic tumors; BCCs, basal cell carcinomas.

[Research advances in the v-raf murine sarcoma viral oncogene homolog gene mutation in ameloblastoma].

V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a pro-oncogene, which is one member of the RAF family. Mutated BRAF is found in approximately 8% of human tumors. BRAF gene mutations lead to continuous activation of the mitogen-activatd protein kinase (MAPK) pathway, which resulting in abnormal cell proliferation and tumorigenesis. In recent years, recurrent MAPK signaling mutations were identified in ameloblastoma, among which BRAF-V600E is the most prominent type. This provides new strategies for the targeted treatment of ameloblastoma. This paper reviewed the latest advances in BRAF gene mutation associated with ameloblastoma and its potential clinical significance.

PTCH mutations in sporadic and Gorlin-syndrome-related odontogenic keratocysts.

Odontogenic keratocysts are relatively common lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (or Gorlin syndrome). The PTCH gene has been reported to be associated with Gorlin syndrome. We investigated 10 cases of non-syndromic keratocysts and two other cases associated with Gorlin syndrome, looking for PTCH mutations. Four novel and 1 known PTCH mutations were identified in five individual patients. Of the 5 mutations identified, 2 were germ-line mutations (2619C>A; 1338_1339insGCG) in 2 cysts associated with Gorlin syndrome, and 3 were somatic mutations (3124_3129dupGTGTGC; 1361_1364delGTCT; 3913G>T) in 3 non-syndromic cysts. This report describes PTCH mutations in both non-syndromic and Gorlin-syndrome-related odontogenic keratocysts in Chinese patients, and suggests that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic keratocysts.

Sympathetic innervation modulates ventricular impulse propagation and repolarisation in the immature rat heart.

OBJECTIVE: When cardiac sympathetic innervation in neonatal rats is retarded by antiserum to nerve growth factor, there is a corresponding increase in the QT interval on ECG. Since the propagation of the cardiac impulse and the repolarisation of cardiac cells both contribute to the QT interval, the aim of this study was to determine the role of sympathetic innervation in modulating ventricular impulse propagation and repolarisation. METHODS: Neonatal rats were treated for the first 10 days of life with nerve growth factor (NGF), its antiserum (As), or placebo. Standard microelectrode techniques were used to study the transmembrane action potential characteristics of subendocardial (ventricular septal) and subepicardial ventricular myocardium. Bipolar surface electrograms were used to record the velocity of impulse propagation and electron microscopy to examine the intercalated discs. RESULTS: In the subendocardium, the phase 0 upstroke velocity of the action potential (dV/dtmax) was lowest in the As treated rats. The latter group also showed the slowest conduction velocity. There were no differences in control action potential durations in the endocardium among the three groups, but in the epicardial tissues, action potential duration was longest in the As treated group. Thus the dispersion in action potential duration was smallest in the As treated animals. Electron microscopic studies of the intercalated discs of ventricular myocytes showed significant enhancement of nexal junction formation in NGF treated rats, whereas As treated animals showed a retarded pattern of both nexal and desmosomal junction formation. CONCLUSIONS: The differences in ultrastructure, conduction, and repolarisation seen in As and NGF treated animals may explain the prolonged QT interval seen in the As treated group.

Deaminovasopressin has direct and modulatory effects on ventricular automaticity in the rat heart.

OBJECTIVE: Some neuropeptides have direct cardiac effects and also modulate the cardiac effects of catecholamines. Vasopressin is an abundantly available neuropeptide having well known interactions with catecholamines in vascular smooth muscle. The aim of this study was to determine the direct and modulatory effects of vasopressin on ventricular automaticity. METHODS: The cardiac effects of deaminovasopressin (dAVP), a long acting synthetic analogue of vasopressin, were tested on basal and alpha 1 agonist induced changes in automaticity in isolated ventricular septal preparations from adult and neonatal rats after chronic exposure (10 micrograms.kg-1 x d-1 subcutaneously for 10 d) and acute exposure (in vitro bath superfusion with 10(-8) M dAVP for 1 h). RESULTS: Chronic exposure to dAVP decreased basal ventricular automaticity in the adult and in 10-11 d old rats. Although alpha 1 agonists tended to decrease automaticity in adult rat heart, prior chronic dAVP exposure altered the chronotropic response to alpha 1 agonist so that only an increase in automaticity was observed. A similar result was seen in adult ventricular septal preparations upon acute superfusion with dAVP. Acute dAVP exposure reduced basal ventricular automaticity, and modified the alpha 1 adrenergic chronotropic response, such that only an increase in automaticity occurred. Acute dAVP exposure in adult ventricular septal preparations did not significantly change total alpha 1 adrenergic receptor density or antagonist affinity, alpha 1 adrenergic receptor subtype expression, or the amount of pertussis toxin sensitive G protein measured in an ADP ribosylation assay. CONCLUSION: dAVP not only exerted direct effects of chronotropy, but also influenced the expression of alpha 1 adrenergic chronotropic responsiveness. If vasopressin has a similar action, this may have important implications in instances where levels of this peptide are raised. For example, surgical stress and cardiopulmonary bypass are clinical situations associated with increases in both vasopressin and catecholamine levels. An interaction between the two may contribute to the development of tachyarrhythmias in these settings.

Plasma neuropeptide Y and catecholamines in pediatric patients undergoing cardiac operations.

OBJECTIVE: Our objective was to assess the sympathoadrenal response in pediatric patients undergoing repair of congenital cardiac defects. METHODS: Plasma catecholamine (norepinephrine and epinephrine) and neuropeptide Y concentrations were quantified before and after cardiopulmonary bypass to assess the response to cardiopulmonary bypass. To determine the response to aortic occlusion, levels of plasma catecholamines and neuropeptide Y were measured at the time of and immediately after release of the aortic crossclamp. RESULTS: During cardiopulmonary bypass, no significant change in levels of plasma norepinephrine (n = 43), epinephrine (n = 37), or neuropeptide Y (n = 46) was observed. Aortic occlusion induced a significant increase in plasma neuropeptide Y, but not in catecholamines. There was a greater increase in plasma neuropeptide Y in children older than age 1 year than in those younger than 1 year. CONCLUSIONS: Plasma neuropeptide Y may be a useful marker of sympathetic nervous system activity. Children younger than age 1 year showed a lesser sympathetic response compared with the response in older children.

Characterization of the alpha1-adrenergic chronotropic response in neuropeptide Y-treated cardiomyocytes.

The cardiac alpha1-adrenergic chronotropic response changes from stimulatory to inhibitory post-natally. The mature inhibitory response is mediated by the alpha1B-adrenoceptor and a pertussis toxin sensitive G protein. In vivo and in vitro studies identify sympathetic innervation as critical for the maturation of this inhibitory response. Additional experiments in a culture model indicate the effect of innervation is dependent on neurally released neuropeptide Y. The present study establishes that the individual signaling elements in the neuropeptide Y induced alpha1-adrenergic cascade are the same as those appearing during normal in vivo development. In addition, the data demonstrate that the effect of neuropeptide Y does not result from activation of the putative cardiac Y3 neuropeptide Y receptor subtype, since it is reproduced by the peptide fragment neuropeptide Y-(13-36) but not by [Leu31, Pro34]neuropeptide Y.

Comparison of techniques for the selection of bacteria-free sperm preparations.

The authors compared the three most commonly used sperm preparation techniques--swim-up, fall-down, and Percoll gradient--for their ability to recover highly motile sperm and minimize bacterial contamination. Eleven human semen samples collected by masturbation were used and run in parallel with the three methods. A semiquantitative bacterial analysis was performed in all samples and results expressed in colony-forming units per milliliter (CFU/ml). The Percoll gradient technique resulted in an average sperm concentration of 5.81 +/- 4.4 X 10(6) ml, and the average bacterial concentration dropped from 8.66 +/- 12.96 X 10(3) CFU/ml in semen to 0.01 +/- 0.03 X 10(3) CFU/ml. The bacterial count was not significantly different when the raw semen was compared with the swim-up or the fall-down preparations. The authors conclude that the Percoll gradient method yields an adequate sperm concentration, with high motility and improved morphology, while eliminating bacterial contamination.

Heart rate variability in neonatal rats after perinatal cocaine exposure.

Pregnant rats received saline once daily (Control QD) or twice daily (Control BID), cocaine 2 mg/kg IV daily (COC QD) or twice daily (COC BID) throughout gestation beginning on gestational day 4. The treatment was continued in nursing mothers until postnatal day 7. All studies were performed in their offsprings on postnatal days 1 and 7. An age-dependent increase in heart rate was observed from D1 to D7 in all four groups of animals. Cocaine exposure significantly increased heart rate in the once daily treatment group on D1 and D7. In contrast, twice daily cocaine exposure did not alter heart rate. Maturational changes in heart rate variability (HRV) were also documented. Low-frequency (LF: 0.25-0.8 Hz) power of HRV is a marker of both sympathetic and parasympathetic influences. and high-frequency (HF: 0.8-2.4 Hz) power is a marker of efferent vagal activity. Total power (TP) is the sum of LF and HF. TP, normalized units of LF (LF as percent of TP), and normalized HF power decreased from D1 to D7 in all groups. Cocaine treatment affected both LF and HF powers and there was an interaction between cocaine treatment and age for both LF and HF. Although LF/HF ratio decreased from D1 to D7 in both groups of control animals. LF/HF did not change from D1 to D7 in either cocaine-treated group. Thus, cocaine exposure significantly attenuated the age-dependent change in LF/HF. Our results indicated that there were normal developmental changes in HRV consistent with continued postnatal development of autonomic nervous system. Perinatal cocaine exposure appeared to modify these changes. The specific autonomic mechanism for the cocaine effect may be a decline in parasympathetic activity and a concomitant change in sympathetic activity.

[Observation on phrenic discharges induced by bicuculline or picrotoxin in spinal rabbits].

The respiratory activity of spinal cord-transected animals was reinvestigated on 71 rabbits. Under light urethane anesthesia and paralyses by gallamine, the spinal cord was transected at either C1 or C2 level, and phrenic discharges were monitored in 43 rabbits. After cordotomy, tonic phrenic discharges were observed in 25 of the 43 spinal rabbits. No spontaneous rhythmic phrenic activities appeared in any of the animal. Respiratory-like, long lasting phrenic bursts (lasting longer than 0.25s) or convulsive-like, short lasting phrenic bursts (lasting shorter than 0.1s on the average) were induced by administration of bicuculline (BCL, 20 micrograms/10 microliters-40 micrograms/20 microliters, intra-subarachnoid space, i.s.s.) in 24 spinal rabbits or picrotoxin (PIC, 20 micrograms/20 microliters, i.s.s. or 3-5 mg/kg i.v.) in 13 spinal rabbits. According to the pattern of the recruitment and de-recruitment of the phrenic discharges, the long lasting phrenic bursts may be divided into three types: Type I, average frequency 23.5 +/- 2.3 cycles/min (BCL), incidence 58.5% (BCL) or 67.7% (PIC); Type II, average frequency 33.8 +/- 4.7 cycles/min (BCL), incidence 39.3% (BCL) or 32.3% (PIC); Type III, average frequency 21.3 +/- 2.8 cycles/min (BCL), incidence 2.2% (BCL) or 3.3% (PIC). The duration of the evoked phrenic discharges was 60.0 +/- 18.9 min (BCL) or 42.0 +/- 0.8 min (PIC). The type I and type II showed respiratory-like discharges, accounting for more than 97.8% of the incidence of the long lasting phrenic bursts. It is suggested that the endogenous GABA system in spinal cord might exert a tonic inhibitory action on the spinal "respiration" activity.