PPA1, an energy metabolism initiator, plays an important role in the progression of malignant tumors.

Inorganic pyrophosphatase (PPA1) encoded by PPA1 gene belongs to Soluble Pyrophosphatases (PPase) family and is expressed widely in various tissues of Homo sapiens, as well as significantly in a variety of malignancies. The hydrolysis of inorganic pyrophosphate (PPi) to produce orthophosphate (Pi) not only dissipates the negative effects of PPi accumulation, but the energy released by this process also serves as a substitute for ATP. PPA1 is highly expressed in a variety of tumors and is involved in proliferation, invasion, and metastasis during tumor development, through the JNK/p53, Wnt/ß-catenin, and PI3K/AKT/GSK-3ß signaling pathways. Because of its remarkable role in tumor development, PPA1 may serve as a biological target for adjuvant therapy of tumor malignancies. Further, PPA1 is a potential biomarker to predict survival in patients with cancer, where the assessment of its transcriptional regulation can provide an in-depth understanding. Herein, we describe the signaling pathways through which PPA1 regulates malignant tumor progression and provide new insights to establish PPA1 as a biomarker for tumor diagnosis.

A randomized, double-blind, double-dummy, multicenter, controlled trial on brotizolam intervention in outpatients with insomnia.

AIM: To investigate the efficacy and safety of brotizolam in outpatients with insomnia. METHODS: This randomized, double-blind, double-dummy, multicenter, controlled trial recruited 253 outpatients randomized to receive either brotizolam (n = 126) or estazolam (n = 127) for 14 days followed by 1 week of follow-up for rebound detection. Sleep Dysfunction Rating Scale (SDRS) and Clinical General Impression Scale were applied for efficacy evaluation. Safety evaluation was based on data regarding vital signs, physical examination, lab tests, ECG and collection of adverse events. RESULTS: Full Analyses Set (FAS) and Safety Set (SS) included data of 251 subjects, with 126 from brotizolam group and 125 from estazolam group. Per Protocol Set (PPS) analysis included data of 235 subjects, with 121 and 114 from each group. After 14 days of treatment, there was no difference with statistical significance between the two groups regarding SDRS total score change from baseline. FAS and PPS analysis showed that the brotizolam is non-inferior to estazolam in efficacy evaluation. There was also no difference with statistical significance regarding rebound rate between brotizolam and estazolam group in FAS. The rate of adverse event in two groups was with no statistically significant difference in SS. CONCLUSION: Brotizolam is effective and safe in relieving the symptoms of insomnia.

Causes and outcomes of persistent vegetative state in a Chinese versus American referral hospital.

OBJECTIVE: To compare the etiologies and clinical outcomes of patients in a persistent vegetative state (PVS) between a Chinese and US referral hospital. METHODS: A retrospective, observational study at the Peking Union Medical College Hospital, Beijing, China and Johns Hopkins Hospital, Baltimore, USA (2001-2010) was performed. RESULTS: There were 36 cases of PVS diagnosed. In Beijing, there were 19 cases: mean age 57 years, range 3-86, (42 %) female, with 37 % of patients observed to survive more than 1 year (range >1 month to >28 years, median >6 months). Causes of PVS in Beijing were hemorrhagic stroke (n = 4, 21 %), ischemic stroke (n = 2, 11 %), cardiac arrest (n = 5, 26 %, including 4 with attempted cardiopulmonary resuscitation (CPR)), traumatic brain injury (n = 3, 16 %), and one each of mitochondrial encephalomyopathy, acute disseminated encephalomyelitis, Lennox Gastaut Syndrome, and epilepsy with craniopharyngioma (n = 4, 21 %). In Baltimore, there were 17 cases of PVS: mean age 43 years, range 15-83, 59 % female, with 41 % observed to survive more than 1 year (range >1 month to >10 years, median >3 years). Causes of PVS in Baltimore were ischemic stroke (n = 3, 18 %), cardiac arrest (n = 3, 18 %, including one with attempted CPR), traumatic brain injury (n = 3, 18 %), neurodegenerative conditions (n = 2, 12 %), and hypoxic ischemic encephalopathy due to respiratory arrest (n = 3, 18 %), metabolic derangements (n = 2, 12 %), and meningitis (n = 1, 6 %). CONCLUSIONS: There may be a long survival period for patients with PVS, including in China where resource constraints exist for acute neurologic care. Stroke appears to be the most common underlying cause of PVS in Chinese patients, followed closely by cardiac arrest with attempted CPR. There appear to be more varied causes of PVS in the US referral hospital with a predominance of stroke, cardiac arrest, and traumatic brain injury.

A functional MRI evaluation of frontal dysfunction in patients with severe obstructive sleep apnea.

BACKGROUND: This study focused on frontal dysfunction during a brief visual delayed matching-to-sample (DMS) task in patients with severe obstructive sleep apnea syndrome (OSAS). We also aimed to assess whether mismatch- or match-task would be more sensitive in the evaluation of OSAS frontal impairment and to determine the factors responsible for the association of the task performance and frontal activation. METHODS: Nine severe OSAS patients and 9 age-matched healthy subjects were studied with an event-related functional magnetic resonance imaging (fMRI). The performance and activation of frontal region of interests (ROIs) were compared between the two groups. The ROIs included anterior cingulate cortices (ACC), anterior prefrontal gyri (aPFG), middle frontal gyri (MFG) and inferior frontal gyri (IFG). The association of reaction time (RTs) and ROIs activation with severe nocturnal hypoxia (as measured by duration of time with oxygen desaturation SaO(2) below 80%) and arousals was estimated. RESULTS: Patients with OSAS showed reduced frontal activation in ACCs, MFGs and IFGs and significantly increased activity in the right aPFG when being involved in mismatch tasks, when compared with healthy subjects. In addition, both the oxygen desaturation duration and arousal index were associated with the slower reaction times (RT) and greater reduction in the frontal activation in ROIs for OSAS patients during mismatch information processing. Other OSAS variables, including apneic index (AI), hypopneic index (HI), desaturation index, and the Epworth Sleepiness Scale (ESS), were not associated with changes in ROI response to either mismatch or match tasks. CONCLUSIONS: Patients with severe OSAS showed decreased mismatch-related activation in frontal ROIs when compared to healthy subjects during a brief visual DMS task. The association of arousal index and severe hypoxia with slow RTs and frontal mismatch-related activation suggests that both hypoxia and sleep fragmentation contributed to frontal dysfunction in OSAS patients. Moreover, the mismatch-related activity is more sensitive than match-related activity in the evaluation of OSAS frontal dysfunction during a brief visual DMS task.

[Clinical study of comparing comorbidity between depression and neurological disorder with depressive disorder].

OBJECTIVE: To compare the clinical traits in comorbidity between depression and neurological disorder with depressive disorder and explore the characteristic of the outpatients with neurological disorder comorbidity in depression. METHODS: According to Diagnosis and Statistic Manual for Mental Disorder-IV (DSM-IV) criteria, outpatients were diagnosed as depressive disorder at Departments of Neurology and Psychology. We used HAMD-17 scale to evaluate the patient's severity. RESULTS: There was no statistical difference in severity of depression in two groups. But the clinical traits showed significant differences between two outpatient groups: the outpatients with neurological disorder comorbidity in depression were elder, had more somatic disorders and a higher retard symptom factor score while the other are relative younger, have less physical disorders and higher the core symptom factor score on the other hand. CONCLUSION: The patients of comorbidity between depression and neurological disorders have unique clinical traits. Thus it will be helpful to improve the identification of diagnosis and choose an appropriate treatment if we know the differences well.

[Clinical traits and treatment outcome for comorbidity of depression and neurological disorders].

OBJECTIVE: To observe the clinical traits and treatment outcome of the comorbidity of depression and neurological disorders. METHODS: For patients diagnosed with depressive disorders based on the diagnostic and statistical manual of mental disorders-IV (DSM-IV) criteria in both outpatients clinics of neurology and psychology. The severity of depression in HAMD-17 scale and quality of life related to outpatients' emotional state and health in Short Form Health Survey (SF-36) were evaluated at the baseline and after a 6-week treatment respectively. RESULTS: Forty-five patients with concurrent depression and neurological disorders and 49 patients with depressive disorders were recruited. The impairs in outpatients with depressive disorder are various degree of both physical health and mental health. The severity of depression and quality of life had a negative correlation. The patients with concurrent depression and neurological disorders were elder and more bodily diseases than those with depressive disorders. According to the SF-36 scores, the patients with concurrent depression and neurological disorders had lower physical function scores (61 and 83, P = 0.044) and higher vitality scores (39 and 29, P = 0.007) than those patients with depression disorders at the baseline. After completing a 6-week treatment, both two groups have the same remission rate and response rate respectively. Bodily pain scores (60 at pre-treatment vs 65 at post-treatment, P = 0.048) changed more obviously in the patients with concurrent depression and neurological disorders. CONCLUSION: More patients with concurrent depression and neurological disorders seek medical consultations at neurological clinics of a general hospital than those with depressive disorders. Their impairment extents of physical health factors were different. And the anti-depressive regimens yield comparable rates of remission and efficacy. If a clinician knows these differences well, the diagnostic and therapeutic levels of the depressive patients will be boosted and their quality of life enhanced.

A mismatch process in brief delayed matching-to-sample task: an fMRI study.

Our previous ERP studies have consistently demonstrated that a negativity N270 elicited by incongruent information in visual S1-S2 matching task represents a type of conflict process, which is distinct from that represented by the classic conflict task or other negative components in delayed matching-to-sample stimulus presentation patterns, since the inter-stimulus interval between S1 and S2 was presented as shorter as 500 ms. The N270 component of ERP was shown to reflect conflict processing during the simple working memory operations. In the present study, a functional MRI (fMRI) was used to investigate the visuospatial characteristics of brain activation associated with the task eliciting N270. The fMRI data showed an increased activation in the right anterior cingulate cortex (ACC, BA 24) and right dorsolateral prefrontal cortex (DLPFC, BA 46), and activation biased to the left occipitotemporal cortex (BA 37) in the incongruent condition. It is suggested that the greater activations of the right ACC coupling with right DLPFC to incongruent task reflect functional efficiency of the right cingulo-prefrontal network during the brief visual delayed period discrimination performance and mismatched information processing.

The language of medically unexplained dyspnea.

BACKGROUND: Medically unexplained dyspnea (MUD) refers to a condition characterized by a sensation of dyspnea and is typically applied to patients presenting with anxiety and hyperventilation without cardiopulmonary explanations for their dyspnea. The diagnosis is difficult. We investigated whether descriptors of dyspnea and associated symptoms of MUD are differentially diagnostic. METHODS: A respiratory symptom checklist incorporating 61 spontaneously reported descriptors of dyspnea was administered to 96 patients with MUD and 195 patients with cardiopulmonary diseases. Symptom factors measuring different qualitative aspects of dyspnea were derived by a principal component analysis. The separation of two patient groups in terms of symptom factors was achieved by a discriminant analysis. RESULTS: Five factors grouped different attributes of dyspnea: urge to breathe, depth and frequency of breathing, difficulty breathing and phase of respiration, wheezing, and affective dyspnea. The other five factors grouped symptoms of anxiety, tingling, cough and sputum, palpitation, and out of control. A discriminant analysis allowed to separate two patient groups (R(2) = 0.45, p < 0.0001). The presence of urge to breathe, affective dyspnea, anxiety, and tingling pointed to the diagnosis of MUD, whereas the reporting of wheezing, cough and sputum, and palpitation indicated cardiopulmonary diseases. The sensitivity was 85%, and specificity was 88%. CONCLUSIONS: Descriptors of dyspnea and associated symptoms allows satisfactory separation of patients with MUD from patients with cardiopulmonary diseases. A prospective study will be required to test the validity and predictive values of the descriptor model in another cohort of patients.

Fearful imagery induces hyperventilation and dyspnea in medically unexplained dyspnea.

BACKGROUND: Medically unexplained dyspnea refers to a condition characterized by a sensation of dyspnea and is typically applied to patients presenting with anxiety and hyperventilation without underlying cardiopulmonary pathology. We were interested to know how anxiety triggers hyperventilation and elicits subjective symptoms in those patients. Using an imagery paradigm, we investigated the role of fearful imagery in provoking hyperventilation and in eliciting symptoms, specifically dyspnea. METHODS: Forty patients with medically unexplained dyspnea and 40 normal subjects matched for age and gender were exposed to scripts and asked to imagine both fearful and restful scenarios, while end-tidal PCO(2) (PetCO(2)) and breathing frequency were recorded and subjective symptoms evaluated. The subject who had PetCO(2) falling more than 5 mmHg from baseline and persisting at this low level for more than 15 seconds in the imagination was regarded as a hyperventilation responder. RESULTS: In patients with medically unexplained dyspnea, imagination of fearful scenarios, being blocked in an elevator in particular, induced anxious feelings, and provoked a significant fall in PetCO(2) (P < 0.05). Breathing frequency tended to increase. Eighteen out of 40 patients were identified as hyperventilation responders compared to 5 out of 40 normal subjects (P < 0.01). The patients reported symptoms of dyspnea, palpitation or fast heart beat in the same fearful script imagery. Additionally, PetCO(2) fall was significantly correlated with the intensity of dyspnea and palpitation experienced during the mental imagery on one hand, and with anxiety symptoms on the other. CONCLUSIONS: Fearful imagery provokes hyperventilation and induces subjective symptoms of dyspnea and palpitation in patients with medically unexplained dyspnea.

[A multiple center study on depression and anxiety state in the department of neurology].

OBJECTIVE: Inpatients of 15 general hospitals were investigated in order to understand the incidence of depression and anxiety state and the patients'quality of life in the Department of Neurology. METHODS: We used Hospital Anxiety and Depression scale (HADS), 17-item Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA) and 36-item Short Form Health Survey (SF-36) as tools to evaluate inpatients' emotional state and health related quality of life within 48 hours after admitted and before discharge, respectively. RESULTS: 610 inpatients were finished admitted evaluation, patients showed clinical depressive symptoms and anxiety symptoms were 123 (20.2%) and 161 (26.4%) respectively, in which including 96 showed the both. 405 inpatients finished discharge evaluation, patients showed clinical depression symptoms and anxiety symptoms were 68 (16.8%) and 93 (23%) respectively, in which including 52 showed the both. Regression analysis indicated that health related quality of life was associated with gender, anxiety and depression state. Only 59 (20.8%) patients received drug treatment during they admitted. There were statistic significance decrease of the HAMA and HAMD total scores between treatment group and non-treatment group when discharged; Vitality, role of emotional and mental health were significantly increased at the time of discharge. CONCLUSION: High rate of depression and anxiety state occurred in the department of Neurology. These abnormal emotions affected the quality of life of patients. If a physician treated somatic diseases only, the depressive and anxiety disturbances could not be remission. Thus, more attention should be paid to give adequate treatment if a patient concomitant presented the emotional disturbances in the general hospital.

Intracranial arterial occlusive lesion in patients with Graves' disease.

OBJECTIVE: To investigate the distribution and clinical manifestations of intracranial arterial occlusive lesions (IAOLs), and their correlation with thyroid function. METHODS: We enrolled 7 patients who had Graves' disease (GD) with IAOLs screened and evidenced by transcranial Doppler, then further confirmed with digital substract angiography in 2 patients and magnetic resonance angiography in 5 patients. Brain magnetic resonance imaging (MRI) was performed in all 7 patients. Three patients were followed up. RESULTS: Among 7 patients, 1 was male and 6 were females. The mean age was 32.0 +/- 5.5 (range from 11 to 49) years old. Six of them had symptoms of GD but one was asymptomatic with abnormality of T3, T4, and thyroid stimulating hormone. The lesions of intracranial arteries were symmetrical bilaterally in the internal carotid artery system in 6 patients, as well as asymmetrical in 1 patient Terminal internal carotid artery (TICA) were involved in all 7 patients. Middle cerebral artery (MCA) were involved in 3, anterior cerebral artery in 2, and basilar artery in 1 patient. Net-like collateral vessels and mimic moyamoya disease were observed in the vicinity of the occlusive arteries in 2 patients. All patients presented symptoms of ischemic stroke including transient ischemic attack and/or infarction while IAOLs were found. Three patients had obvious involuntary movements. Brain MRI revealed infarctions located in the cortex, basal ganglion, or hemiovular center in 5 patients. The remaining 2 patients had normal brain MRI. The neurological symptoms were improved concomitant with relief of the thyroid function in 2 patients, while IAOLs were aggravated with deterioration of the thyroid function in 1 patient. CONCLUSION: IAOLs in patients with GD mainly involve intracranial arteries, especially the TICA and MCA, which is similar to moyamoya disease. The neurological symptoms and severity of involved arteries may relieve while the hyperthyroidism is gradually under control.

Respiratory complaints in Chinese: cultural and diagnostic specificities.

STUDY OBJECTIVES: We investigated the qualitative components of a wide range of Chinese descriptors of dyspnea and associated symptoms, and their relevance for clinical diagnosis. MEASUREMENTS: Sixty-one spontaneously reported descriptors were elicited in Chinese patients to make a symptom checklist, which was administered to new groups of patients with different cardiopulmonary diseases, to patients with medically unexplained dyspnea and to healthy subjects. RESULTS: Test-retest reliability was satisfactory for most of the descriptors. A principal component analysis on 61 descriptors yielded the following eight factors: dyspnea-effort of breathing; dyspnea-affective aspect; wheezing; anxiety; tingling; palpitation; coughing and sputum; and dying experience. Although the descriptors of dyspnea-effort of breathing resembled Western wordings and were shared by patients with a variety of diseases, the descriptors of dyspnea-affective aspect appeared to be more culturally specific and were primarily linked to the diagnosis of medically unexplained dyspnea, whereas wheezing was specifically linked to asthma. CONCLUSIONS: Three factors of breathlessness were found in Chinese. The descriptors of dyspnea-effort of breathing and wheezing appear to be similar to Western descriptors, whereas the dyspnea-affective aspect seems to bear cultural specificity.

Distinctive conflict processes associated with different stimulus presentation patterns: an event-related potential study.

Twelve subjects were asked to perform visual stimulus presentation tasks. Two figures were presented either simultaneously or sequentially. They were either in congruity (same shapes) or in conflict (different shapes) with each other. Conflicting stimulus pairs presented sequentially evoked a negative event-related component with a fronto-central and bilateral posterior scalp distribution, referred to as N270. In contrast, stimuli displayed simultaneously elicited a N220 with fronto-central prominence, irrespective of whether they were in conflict or in congruity. The results suggest that the N270 may be associated with the processing of a conflict with working memory information whereas the N220 might reflect the detection and evaluation of attention to visual information in the human brain.

[Medically unexplained dyspnea in children: a review of 34 cases].

OBJECTIVE: Medically unexplained dyspnea is common in adult and accounts for 14% patients complaining of dyspnea. Its occurrence in children is seldom recognized. In the present paper, 34 children with medically unexplained dyspnea (age 10 to 18 years) seen in Peking Union Medical College Hospital from 1996 to 2002 are reported. METHODS: The diagnosis of medically unexplained dyspnea was clinical: it was based on the presence of dyspnea and other complaints which cannot be explained by an organic disease. The patients answered Nijmegen questionnaire and state and trait anxiety (STAI), and performed hyperventilation provocation test. Twenty sessions of breathing therapy were applied and 13 out of 34 children were followed up after the therapy. RESULTS: Among the children, 75% started to have symptoms at the age of 13 to 16 years, though the age of first episode could be as early as 8 years. In most of the cases, the course was chronic clinically. In addition to marked dyspnea, their clinical profile included symptoms of hyperventilation i.e. blurred vision, dizziness, tingling, stiff fingers or arm. The symptoms of anxiety were less frequent in children and accordingly the level of anxiety evaluated by means of STAI was lower in children compared to adult patients. The precipitating psychological factors appeared to be related to middle school competition. Pressure from exams, reprimand from stern and unsympathetic teachers coupled with high parental expectation could be emotionally damaging to psychologically susceptible children. Thirteen patients were followed up after 2-3 months of breathing therapy with emphasis on abdominal breathing and slowing down of expiration. After therapy, the sum score of the Nijmegen Questionnaire was markedly decreased. Dyspnea and symptoms of hyperventilation were improved. The level of anxiety was minimally modified. CONCLUSION: The cases illustrated the need for careful diagnostic evaluation and treatment because of the high rate of chronicity of the disorder.

[Diagnosis and treatment of medically unexplained dyspnea].

Medically unexplained dyspnea refers to a group of patients presenting marked dyspnea without structural alterations of organs/systems after thorough examinations. This clinically neglected group of patients accounts for about 14% of patients with dyspnea in secondary health care. They appear very difficult to manage clinically. In this paper an organized approach used to diagnose medically unexplained dyspnea is presented. Breathing re-training is recommended as a therapy for those "difficult to treat patients".

Assessment of the therapeutic activity of a combination of almitrine and raubasine on functional rehabilitation following ischaemic stroke.

BACKGROUND AND OBJECTIVES: Stroke is a major cause of disability. Certain experimental studies have suggested that a combination of almitrine + raubasine (Duxil) increases the supply of oxygen to cerebral tissues and may be beneficial in post-stroke rehabilitation. This multicentre clinical study was carried out in order to assess the efficacy of this combination on poststroke rehabilitation. METHODS: The trial was a randomised, double-blind, placebo-controlled study. Patients that had experienced an ischaemic cerebrovascular accident (confirmed by CT scan) were included 4-6 weeks after the acute onset and received randomised treatment of either almitrine + raubasine or placebo 2 tablets daily for 3 months. Before treatment, there was a 2-week washout period for stopping all other drugs, except for antihypertensive and antidiabetic drugs. We assessed the patients by Barthel Index (BI), Neurological Functional Deficit Scores (NFDS), and Hasagawa Dementia Scales (HDS) each month after treatment. RESULTS: A total of 83 patients were entered into the study and data were available for 74. Of these, 38 patients received almitrine + raubasine and 36 received placebo. The baseline characteristics were comparable between both groups. Almitrine + raubasine was significantly more effective than placebo at increasing BI at 1, 2 or 3 months (14.6 +/- 13.8 versus 3.3 +/- 13.2, p = 0.01; 19.3 +/- 13.6 versus 8.8 +/- 14.0, p = 0.02; 22.6 +/- 14.7 versus 10.7 +/- 17.0, p = 0.02 respectively) and reducing NFDS at 1 month (3.6 +/- 3.2 versus 1.9 +/- 3.5, p = 0.034) after treatment. More almitrine + raubasine-treated patients' NFDS had improved compared with placebo-treated patients at 2 and 3 months (97 versus 78%, p = 0.013; 100 versus 86%, p = 0.023 respectively). Compared with pretreatment, there was a strong tendency towards an improvement of HDS with almitrine + raubasine. The number of adverse events reported was low for the almitrine + raubasine-treated group and the placebo group and all events were mild, of short duration and resolved without treatment. Almitrine + raubasine had no clinically significant effect on blood pressure, heart rate or other laboratory tests. CONCLUSION: The results indicate that almitrine + raubasine can accelerate neurological function recovery after stroke to some degree and is well tolerated.

Medically unexplained dyspnea: psychophysiological characteristics and role of breathing therapy.

BACKGROUND: Medically unexplained dyspnea occurs commonly in medical settings and remains poorly understood. This study was conducted to investigate the psychophysiological characteristics of medically unexplained dyspnea and the efficacy of breathing retraining for these patients. METHODS: A group of patients with medically unexplained dyspnea were compared to patients with a variety of organic lung diseases and healthy subjects. In another group of patients, the influence of breathing therapy on complaints, anxiety, and breath-holding was evaluated for an average of 1.5 years. RESULTS: Patients with medically unexplained dyspnea reported more intense dyspnea than patients with a variety of organic lung diseases. Additionally, they were anxious and presented a broad range of symptoms in daily life and under challenge, for instance voluntary hyperventilation. More than one third of them qualified for panic disorder. They had shorter breath-holding time at rest, less increase in breath-holding time and higher chances of showing a "paradoxical" decrease of breath-holding time after hyperventilation. A combination of PaO2, forced expiratory volume in one second (FEV1), and anxiety measures distinguished them from organic dyspnea. Breathing retraining profoundly improved their symptoms and decreased the level of state and trait anxiety. Moreover, they better tolerated the voluntary hyperventilation and the symptoms induced were also markedly decreased after therapy. Breath-holding time was prolonged and PetCO2 in a representative group of patients increased. CONCLUSIONS: Patients with medically unexplained dyspnea appear to have the feature of a "psychosomatic" patient: an anxious patient with a wide variety of symptoms of different organ systems that do not have an organic basis. They can be distinguished from organic dyspnea using a small set of physiological and psychological measures. Breathing retraining turns out to be an effective therapy for those "difficult to treat patients".