Glycyrrhizin inactivates toll-like receptor (TLR) signaling pathway to reduce lipopolysaccharide-induced acute lung injury by inhibiting TLR2.

OBJECTIVE: This study aimed to explore glycyrrhizin on acute lung injury (ALI) and how glycyrrhizin (GL) attenuated lipopolysaccharide (LPS)-induced ALI. METHODS: Bioinformatics analysis was performed to screen the expressed genes in LPS-induced ALI mice. The enrichment of functions and signaling pathways of deregulated genes were conducted. Combined with DIGSEE and STICH, the target gene for further investigation was chosen. To verify target gene in mice, we performed experiment in vivo. Forty mice were randomized into NC, LPS, LPS + S, and LPS + GL group. Mice in the LPS + GL group received glycyrrhizin l mg and mice in LPS + S received saline. Then, HE and Masson staining detected pathological changes of lung tissues; enzyme-linked immunosorbent assay analyzed bronchoalveolar lavage fluid concentrations of MIP-2, mice growth-related oncogene homologue (KC), IL-4, IL-6, GM-CSF, IFN-γ, and IgM; western blot analysis determined the expression of toll-like receptor (TLR) signaling and NF-κB pathway-related proteins. RESULTS: Tlr2 which was not only upregulated but also closely related to glycyrrhizin. TLR2 was upregulated in following LPS induced in cells and TLR2 overexpression-activated TLR signaling pathway to promote ALI. After glycyrrhizin treatment, the expression of TLR2 was reduced. Furthermore, it was found out that the number of inflammatory cells, collagen deposition, MIP-2, KC, IL-4, IL-6, GM-CSF, and IFN-γ expression increased in ALI mice and glycyrrhizin mitigated it. Similarly, the expression of TLR signaling pathway and NF-κB pathway-related protein also increased. CONCLUSION: Glycyrrhizin functioned as a suppressor in TLR signaling pathway to reduce LPS-induced ALI by inhibiting TLR2.

Transient upregulation of TASK-1 expression in the hypoglossal nucleus during chronic intermittent hypoxia is reduced by serotonin 2A receptor antagonist.

Hypoglossal motoneurons innervate genioglossus muscle, the contraction of which is critical in the maintenance of upper airway patency in patients with obstructive sleep apnea. As a potassium channel distributed in hypoglossal motoneurons, TWIK-related acid-sensitive K+ channel-1 (TASK-1) could be inhibited by 5-HT. This study aimed to investigate if TASK-1 expression in hypoglossal nucleus could be influenced by chronic intermittent hypoxia (CIH) and 5-HT2A receptors antagonist. Two hundred twenty-eight rats were exposed to CIH or normoxia (NO) in the presence and absence of 5-HT 2A receptor antagonist (MDL-100907) microinjected into the hypoglossal nucleus. The expression of 5-HT and TASK-1 in the hypoglossal nucleus were detected by immunohistochemistry and reverse transcription quantitative polymerase chain reaction on the 1st, 3rd, 7th, 14th and 21st day of CIH exposure. The mean optical density (MOD) of 5-HT in the XII nucleus was significantly increased in the CIH and CIH + MDL group than the NO group on the 7th and 21st day ( p < 0.05). Compared with the NO group, the MOD and gene expression of TASK-1 in the CIH group was significantly increased on the 7th and 14th day ( p < 0.05), then normalized on the 21st day. The TASK-1 expression in the CIH + MDL group was significantly lower than the CIH + PBS and CIH group on the 7th and 14th day ( p < 0.05). The CIH-induced transiently upregulation of the TASK-1 expression in the hypoglossal nucleus could be reversed by 5-HT 2A receptor antagonist, indicating that the modulation of the TASK-1 expression in response to CIH involves 5-HT and 5-HT 2A receptors, and this CIH effect might be 5-HT 2A receptor-dependent.

Frequency of the acquired resistant mutation T790 M in non-small cell lung cancer patients with active exon 19Del and exon 21 L858R: a systematic review and meta-analysis.

BACKGROUND: Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations, subsequent drug resistance is almost inevitable. The specific mechanisms of EGFR-TKI drug resistance can be identified through repeat biopsy. METHODS: To better understand the clinical characteristics of TKI resistance in NSCLC patients, we retrospectively reviewed studies of acquired TKI drug resistance using repeat biopsy from the last decade. The relevant literature was retrieved from January 2005 to August 2015 in the databases Medline and Embase. The search terms were NSCLC or non-small cell lung cancer and T790 M. RESULTS: A total of 478 patients with NSCLC tested by repeated biopsy were confirmed to have acquired TKI resistance. Analysis indicated that 240 patients (50.21%) of the 478 patients with acquired TKI drug resistance had the T790 M mutation. The detection rate of T790 M in different repeat biopsy sites was also different, with the highest positive rate in the lymph nodes (60%) and the lowest detection rate in cerebrospinal fluid (less than 5%). In addition, patients with T790 M had longer overall survival compared to those without the mutation (P < 0.05). Of the 240 patients with T790 M mutations, 213 patients showed results consistent with the mutation analysis before TKI treatment, and the rate of patients with the L858R point mutation along with the T790 M mutation was lower than that of patients with the exon 19 deletion (36.42% to 58.30%). CONCLUSIONS: T790 M occurred more frequently in patients with the exon 19 deletion than in those with exon 21 L858R, which gave the survival benefit of the T790 M mutation and may explain why patients with the exon 19 deletion had an improved overall survival.

Placental growth factor signaling regulates isoform splicing of vascular endothelial growth factor A in the control of lung cancer cell metastasis.

Vascular endothelial growth factor (VEGF) family members play critical and complex roles in the regulation of cancer vascularization and metastasis. The exact molecular control of lung cancer metastasis by VEGF family members is not completely understood. Here, we showed that specimens from non-small cell lung cancer (NSCLC) contained significantly higher levels of placental growth factor (PlGF) than paired non-cancer tissue (p < 0.05, N = 25). Moreover, higher levels of PlGF were detected in NSCLC specimens from the patients who had distal metastases than those who had not. High-PlGF levels appeared to be associated with poor patient survival. In vitro, PlGF dose-dependently increased the ratio of pro-angiogenic VEGF isoform (VEGF165) versus anti-angiogenic VEGF isoform (VEGF165b), seemingly through induction of expression of splicing regulatory factor SRp40, resulting in the enhancement of the cancer cell metastatic potential. Higher levels of SRp40 were detected in NSCLC specimens, compared to paired non-cancer tissue (p < 0.05, N = 25). Finally, a strong correlation was detected between the levels of PlGF and SRp40 in NSCLC specimens (r = 0.83, p < 0.0001, N = 25). Together, these data suggest that PlGF may increase NSCLC metastasis through SRp40-mediated mRNA splicing of VEGF.

Analysis of non-small cell lung cancer microenvironment indicates preponderance of T cell exhaustion marker expression.

Lung cancer metastasis causes 70% of an estimated 1.4 million deaths per annum. The major shortcoming in lung cancer is the tendency to have inherent or develop acquired resistance to chemotherapy. It is now evolving that such resistance might develop due to differential contribution and interaction with tumor microenvironment, stromal cells, and the extracellular matrix. The objective of the current study was to define the lung cancer tumor microenvironment. We have identified multiple tumor-infiltrating T lymphocyte subsets in patients with lung cancer, which were independent of disease stage. Functional analysis indicated high expression of the inhibitory receptors, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activated gene 3 (LAG3) and programmed cell death protein 1 (PD-1) in both CD4 and CD8 subsets, compared to non-malignant controls. Inhibitory receptors expressed by the tumor infiltrating T cells might mediate tolerance to tumor antigens with co-expression of these receptors exacerbating lung carcinogenesis and metastatic progression.

Kinesin family member 2A promotes cancer cell viability, mobility, stemness, and chemoresistance to cisplatin by activating the PI3K/AKT/VEGF signaling pathway in non-small cell lung cancer.

Kinesin family member 2A (KIF2A), a member of the kinesin-13 protein family that functions as a regulator in mitosis, neuron branch extension, etc., is reported to be involved in the pathogenesis of multiple cancers. This study assessed KIF2A effects on cancer cell functions and sensitivity to chemotherapy and its interaction with PI3K/AKT/VEGF signaling when mediating cancer cell functions, and chemosensitivity in non-small cell lung cancer (NSCLC). Human bronchial epithelial cell line BEAS-2B and human NSCLC cell lines NCI-H1299, NCI-H385, NCI-H1650, and A549 were used. The KIF2A and negative control (NC) overexpression plasmids were transfected into A549 cells; KIF2A and NC knock-down plasmids were transfected into NCI-H1299 cells. Rescue experiments were conducted by transfecting PI3K and NC knock-down plasmids into KIF2A overexpression A549 cells and transfecting PI3K and NC overexpression plasmids into KIF2A knock-down NCI-H1299 cells. Proliferation, apoptosis, migration, invasion, CD133+ proportion, sensitivity to chemotherapeutics, and PI3K/AKT/VEGF pathway were assessed. KIF2A mRNA and protein expression levels were elevated in NCI-H1299, NCI-H385, NCI-H1650, and A549 cells compared to BEAS-2B cells. KIF2A overexpression elevated proliferation, migration, invasion, stemness, and resistance to cisplatin but did not affect apoptosis or resistance to pemetrexed in A549 cells. Furthermore, KIF2A knock-down repressed proliferation, migration, invasion, stemness, and resistance to cisplatin, but not to pemetrexed, and it enhanced apoptosis in NCI-H1299 cells. Rescue experiments showed that the PI3K/AKT/VEGF pathway compensated for KIF2A effects on cell functions and sensitivity to cisplatin in A549 and NCI-H1299 cells. In conclusion, KIF2A advocates NSCLC cell viability, mobility, stemness, and chemoresistance to cisplatin by activating the PI3K/AKT/VEGF signaling pathway.

The efficacy and tolerance of prone positioning in non-intubation patients with acute hypoxemic respiratory failure and ARDS: a meta-analysis.

BACKGROUND AND AIMS: The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS. METHODS: We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% [95% confidence interval (CI): 0.26-0.42, I2 = 25%], 4% (95% CI: 0.01-0.07, I2 = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01-0.12, I2 = 5%). Prone positioning increased PaO2/FiO2 [mean difference (MD) = 47.89, 95% CI: 28.12-67.66; p < 0.00001, I2 = 67%] and SpO2 (MD = 4.58, 95% CI: 1.35-7.80, p = 0.005, I2 = 97%), whereas it reduced respiratory rate (MD = -5.01, 95% CI: -8.49 to -1.52, p = 0.005, I2 = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO2/FiO2 and SpO2 were significantly improved in COVID-19 patients and non-COVID-19 patients. CONCLUSION: Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS.The reviews of this paper are available via the supplemental material section.

[Risk factors of novel severe influenza A(H1N1) with concurrent adult respiratory distress syndrome].

OBJECTIVE: To analyze the risk factors of novel severe influenza A (H1N1) with concurrent adult respiratory distress syndrome (ARDS). METHODS: A multivariable Logistic regression analysis was conducted for ARDS risk factors in controlled clinical trials for comparing the clinical features between the ARDS and non-ARDS groups and comparing ARDS patients' lymphocyte counts and T lymphocyte subsets between the smoking and non-smoking groups through a retrospective analysis of 92 novel influenza A (H1N1) patients who admitted to our hospital from October 2009 to January 2010. RESULTS: Through a single factor analysis between ARDS and non-ARDS groups, the comparisons in the factors including smoking (17 cases vs 11 cases), T lymphocyte subsets, lactate dehydrogenase (LDH), initial treatment point of oseltamivir and initial oxygen flow greater than 2 L/min (28 cases vs 18 cases) had statistically significant differences (all P<0.05). The comparison in T lymphocyte subsets had statistically significant difference between the smoking and non-smoking groups in ARDS patients (all P<0.05). The multivariable Logistic regression analysis showed that smoking (P=0.027, OR=8.05, 95%CI: 1.28-50.80) and initial oxygen flow greater than 2 L/min (P=0.010, OR=16.70, 95%CI: 3.29-84.84) were relevant to the incidence of ARDS in novel influenza A (H1N1) patients. CONCLUSION: Smoking and initial oxygen flow greater than 2 L/min were the risk factors of novel severe influenza A (H1N1) with concurrent ARDS.

[Expression and activation of hypoxia inducible factor-1alpha and iNOS in the brain of rats with chronic intermittent hypoxia].

OBJECTIVE: To study the expression of iNOS and hypoxia inducible factor-1 (HIF-1)alpha in the brain of rats under chronic intermittent hypoxia, and therefore to explore the molecular mechanisms of hypoxia induced reactions in the nervous system according to the measure of HIF-1 transcription activity. METHODS: Male Wistar rats were divided into 3 groups: a chronic hypoxia group (n = 8, breathing 10%O2 for 8 h per day), an intermittent hypoxia group (n = 8, breathing 10%O2 and air altered per 90 sec for 8 h per day) and a control group (n = 8, breathing air). Thirty days later, the expression of HIF-1alpha and iNOS was assessed by using immunohistochemical methods and Western blot, and HIF-1alpha and iNOS mRNA was assessed by RT-PCR. The detection of binding activity of HIF-1 to the iNOS promoter gene was assessed by electrophoretic mobility shift assay. RESULTS: The productions of HIF-1alpha (508 +/- 77, 1118 +/- 106 and 1937 +/- 119) and iNOS (673 +/- 82, 1325 +/- 139 and 2088 +/- 130) were the highest in the intermittent hypoxia group. Only weaker binding activity between HIF-1 and iNOS promoter gene was detected in the control group, but the binding activity was increased significantly in the intermittent hypoxia group. CONCLUSIONS: Hypoxia, especially intermittent hypoxia, can cause increased expression of iNOS and HIF-1alpha. HIF-1 may be a key factor in up-regulation of the transcription of iNOS under chronic intermittent hypoxia. HIF-1 promotes the transcription of iNOS though enhanced binding activity.

Verifying the Relative Efficacy between Continuous Positive Airway Pressure Therapy and Its Alternatives for Obstructive Sleep Apnea: A Network Meta-analysis.

Obstructive sleep apnea (OSA) is a common breathing disorder, and continuous positive airway pressure (CPAP) therapy together with its alternatives has been developed to treat this disease. This network meta-analysis (NMA) was aimed to compare the efficacy of treatments for OSA. Cochrane Library, MEDLINE, and Embase were searched for eligible studies. A conventional and NMA was carried out to compare all therapies. Sleeping characteristics, including Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), arterial oxygen saturation, and arousal index (AI), and changes of blood pressure were selected as outcomes. A total of 84 studies were finally included after rigorous screenings. For the primary outcomes of AHI and ESS, the value of auto-adjusting positive airway pressure (APAP), CPAP, and oral appliance (OA) all showed statistically reduction compared with inactive control (IC). Similar observation was obtained in AI, with treatments of the three active interventions. A lower effect of IC in SaO2 was exhibited when compared with APAP, CPAP, and OA. Similar statistically significant results were presented in 24 h systolic blood pressure and 24 h DBP when comparing with CPAP. Our NMA identified CPAP as the most efficacious treatment for OSA patients after the evaluation of sleeping characteristics and blood pressures. In addition, more clinical trials are needed for further investigation due to the existence of inconsistency observed in this study.

Association of Obstructive Sleep Apnea with Asthma: A Meta-Analysis.

This study evaluates the relationship between obstructive sleep apnea (OSA) and asthma. Literature search was carried out in several electronic databases and random effects meta-analyses were performed to obtain pooled estimates of the prevalence of OSA, OSA risk and sleep disordered breathing (SDB) in asthma patients and pooled odds ratios of the prevalence between asthma and non-asthma patients. In adult asthma patients, the prevalence [95% confidence interval] of OSA, OSA risk, and SDB was 49.50 [36.39, 62.60] %, 27.50 [19.31, 35.69] %, and 19.65 [14.84, 24.46] % respectively. The odds of having OSA, OS risk and SDB by the asthma patients were 2.64 [1.76, 3.52], 3.73 [2.90, 4.57] and 1.73 [1.11, 2.36] times higher (p < 0.00001 for all) in asthma than in non-asthma patients, respectively. Adult asthma patients with OSA had significantly higher BMI in comparison with asthma patients without OSA. This study reveals that the prevalence of OSA in asthma patients is considerably higher; even higher than OSA risk and SDB. Sleep studies should be performed in asthma patients with symptoms suggestive of OSA/OSA risk/SDB.

[The analysis of risk factors correlated to pulmonary hypertension in obstructive sleep apnea syndrome patients during awake state].

OBJECTIVE: To investigate the development of pulmonary hypertension in obstructive sleep apnea syndrome (OSAS) patients and to analyze the correlated factors. METHODS: Pulmonary arterial pressure was monitored by right cardiac catheterization in 15 OSAS patients, and simultaneously polysomnography was performed. Blood gas analysis and lung function were also measured. RESULTS: Pulmonary arterial pressure at awake state was correlated positively to mean maximal pulmonary pressure during sleep, body mass index (BMI) and hemoglobin (Hb), but negatively to PaO2, the percent predicted forced vital capacity (FVC% pred). Compared with OSAS patients without pulmonary hypertension, the BMI, PaCO2, and Hb of OSAS patients with pulmonary hypertension increased significantly, while FVC% pred and PaO2 decreased. Stepwise linear regression indicated that pulmonary arterial pressure at awake state was closely correlated with mean maximal pressure during sleep (beta = 0.35, standard error 0.10, R(2) = 0.89, P = 0.006) and PaCO2 (beta = 0.72, standard error 0.27, R(2) = 0.94, P = 0.022), and mean maximal pulmonary arterial pressure during sleep was closely correlated to PaCO2, BMI, PaO2 and the ratio of arterial pressure and oxygen concentration during rapid eye movement sleep (RDeltaPAP/DeltaSpO2). The regression equation was y' = -152.70 + 1.92 PaCO2 + 1.37 BMI + 0.67 PaO2 + 16.29 RDeltaPAP/DeltaSpO2. CONCLUSION: Pulmonary arterial pressure increasing in OSAS patients is induced mainly by hypercapnia and hypoxia at day time, and related to forced ventilation capacity, BMI and the ratio of pulmonary arterial pressure and oxygen concentration variation during rapid eye movement sleep. There was no obvious relation between pulmonary arterial pressure and apnea index.

[Endothelium-dependent vasodilation in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To evaluate the endothelial function in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) by measuring the brachial artery diameter during reactive hyperemia. METHODS: Thirty patients with OSAHS (8 with mild and 22 with moderate/severe OSAHS) and 10 control subjects were studied. Brachial artery diameter was measured with Doppler ultrasound under baseline conditions, during reactive hyperemia (an endothelium-dependent dilatation) and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator). The dilative rate of brachial artery in different conditions was calculated to evaluate the endothelial function. RESULTS: The dilative rate of brachial artery in the control group, the mild OSAHS group and the moderate/severe OSAHS group were (15.2 +/- 2.6)%, (14.3 +/- 3.2)% and (9.8 +/- 4.9)%, respectively. There was a significant decrease of endothelium-dependent flow-mediated dilation in the moderate/severe OSAHS group compared to the control group and the mild OSAHS group. No significant difference in endothelium-independent vasodilator after sublingual administration of nitroglycerin was found among the three groups. CONCLUSION: Patients with moderate/severe OSAHS have impaired endothelium-dependent vasodilatation, and OSAHS itself maybe a risk factor for endothelial dysfunction.

[Regulation of hypothalamus-pituitary-adrenal axis and growth hormone axis in obstructive sleep apnea-hypopnea syndrome patients].

OBJECTIVE: To explore the regulation of hypothalamus-pituitary-adrenal (HPA) axis and growth hormone (GH) axis in obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: OSAHS patients (OSAHS group) and subjects with obesity alone (control group) were monitored by polysomnography (PSG). The corticotropin-releasing hormone (CRH), growth hormone releasing hormone (GHRH), corticotropin (ACTH), cortisol and growth hormone levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay before and after sleep. Their correlation were analyzed. RESULTS: The CRH concentration [(1.66 +/- 0.34), (4.96 +/- 0.98) mmol/L before and after sleep] and cortisol content [(152.93 +/- 136.15), (445.53 +/- 123.09) microg/L before and after sleep] in the OSAHS group were significantly higher than those of the control group [CRH was (0.67 +/- 0.42), (2.27 +/- 1.10) mmol/L, cortisol concentration was (68.94 +/- 20.13), (146.05 +/- 30.48) microg/L, before and after sleep, respectively, all P < 0.01]; GHRH significantly decreased in the OSAHS group [(1.42 +/- 0.07), (1.01 +/- 0.05) mmol/L before and after sleep] compared with the control group [(1.99 +/- 0.34), (1.58 +/- 0.15) mmol/L, respectively; all P < 0.01]; but there was no difference in growth hormone. The ratio of the variation of CRH, GHRH level (DeltaCRH/DeltaGHRH) was significantly higher in the OSAHS group (285.02 +/- 143.32) than that in the control group (71.15 +/- 15.37, P < 0.01). The bivariate correlation analysis of the OSAHS group indicated that DeltaCRH/DeltaGHRH was correlated positively with average awake duration (r = 0.882), but negatively with average blood oxygen concentration (r = -0.696). The average blood oxygen concentration was negatively correlated with average awake duration (r = -0.729). CONCLUSIONS: There are abnormal changes of HPA axis and GH axis in OSAHS patients, and the feedback regulation is disordered. These abnormalities are related to sleep structure variation and hypoxia during sleep.

Association of Dietary Vitamin A and ß-Carotene Intake with the Risk of Lung Cancer: A Meta-Analysis of 19 Publications.

Whether dietary ß-carotene and vitamin A intake protect against lung cancer risk is not clear. Therefore, we performed this meta-analysis to investigate the association between them. The related articles were searched using the databases PubMed and the Web of Knowledge up to May 2015. We used the random-effect model to estimate the relative risk (RR) and their 95% CI. Small-study effect was assessed using Egger's test. In total, 19 studies comprising 10,261 lung cancer cases met the inclusion criteria. The pooled RR and their 95% CI was 0.855 (0.739-0.989) for higher category of dietary vitamin A intake and lung cancer risk, especially among Asian populations and in the cohort studies. Evidence from 18 studies suggested that higher category of dietary ß-carotene intake could reduce lung cancer risk (0.768 (0.675-0.874)).The associations were also significant in American and Asian populations. In conclusions, higher category of dietary ß-carotene and vitamin A intakes could reduce the risk of lung cancer. However, the dose-response analysis was not performed due to the limited data in each individual study. Due to this limitation, further studies with detailed dose, cases and person-years for ß-carotene and vitamin A of each category are wanted to assess this dose-response association.

Porphyria cutanea tarda and Sjogren's syndrome.

Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren's syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren's syndrome.

Porphyria cutanea tarda and Sjogren's syndrome

Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren's syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren's syndrome.

[The effect of chronic intermittent hypoxia to hypothalamus-pituitary-adrenal axis and growth hormone level in rats during sleep].

AIM: To research the effect of intermittent hypoxia during sleep on hypothalamus-pituitary-adrenal (HPA) axis and growth hormone (GH) level. METHODS: Rats were respectively exposed to intermittent hypoxia, room air and continuous hypoxia, after 1 day, 3 days, 7 days and 30 days, mRNA levels of corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH) in hypothalamus of rats were detected using RT-PCR, and the levels of CRH, GHRH, corticotropin(ACTH), cortex ketone, and growth hormone in plasma were measured. RESULTS: After 30 days, the CRH mRNA levels in rats hypothalamus which exposed to intermittent hypoxia were increased significantly than those exposed to continuous hypoxia as well as normal control but GHRH decreased, there was no difference between continuous hypoxia and normal control. After 1 day, 3 days, and 7 days, there was no difference between continuous hypoxia and intermittent hypoxia. After 30 days, the plasmic level of CRH,ACTH and cortex ketone increased, GHRH decreased and GH had no obvious change. CONCLUSION: The rats' HPA axis level increases and GHRH restrained with chronic intermittent hypoxia during sleep, feedback regulation disorders.