To evaluate the incidence and factors related to daytime CO2 retention (PaCO2 ≥ 45 mm Hg, 1 mm Hg = 0.133 kPa) in Chinese patients with obstructive sleep apnea hypopnea syndrome.1441 patients with OSAHS had daytime arterial blood gas analysis were recruited from 2007 to 2009 in Peking University People's Hospital. 145 patients underwent pulmonary function test and had FEV1/FVC ratio over 70% were under further analysis. Sex, age, BMI, pulmonary function, polysomnography (PSG) and blood gas analysis results were recorded. Linear regression analysis was used to evaluate the relationship between PaCO2 levels and related parameters. Comparison was done between hypercanpnic and eucapnic patients.Daytime hypercapnia occurred in 25.2% of the 1441 patients with OSAHS, and 26.9% in the 145 OSAHS patients who had lung function test and with FEV1/FVC ratio over 70%. PaCO2 was correlated with BMI, PaO2 and the severity of nocturnal hypoxemia as reflected by the mean SpO2 and SIT90. This was also confirmed by the comparison between the hypercapnic and eucapnic patients.Hypercapnia occurs in a large part of patients with OSAHS and normal FEV1/FVC. BMI, nocturnal hypoxemia and daytime PaO2 level are all contributed to the development of daytime CO2 retention in OSAHS.
Cervical cancer is a common female malignant tumor that seriously threatens human health. This study explored the anticervical cancer effects and potential mechanisms of Rotundifuran (RTF), a natural product isolated from Vitex trifolia L. In this study, we found that RTF can suppress the proliferation of cervical cancer cell lines, including HeLa and SiHa cells (with the IC 50 less than 10 μ M), via induction of apoptosis in vitro , and the antitumor effect of RTF is further confirmed on the HeLa cell‐inoculated xenograft model. In addition, our results proved that the antitumor effects of RTF might be related with the reactive oxygen species‐ (ROS‐) induced mitochondrial‐dependent apoptosis through MAPK and PI3K/Akt signal pathways. Using proteomics analysis and the drug affinity responsive target stability‐ (DARTS‐) combined mass spectrometry (DARTS‐MS), Cyr61 was indicated as a potential target for RTF in cervical cancer cells. Our present study would be beneficial for the development of RTF as a candidate for treatment of cervical cancer in the future.
Introduction: Currently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies demonstrated robust low density lipoprotein cholesterol (LDL-C)-lowering efficacy at doses up to 420 mg monthly, while longer dosing intervals are largely unexplored. We assessed the efficacy and safety of tafolecimab, a potential long-acting fully human PCSK9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia (ClinicalTrials.gov, NCT04289285). Methods: Patients were randomized 2:2:1:1 to receive subcutaneous tafolecimab 450 mg every 4 weeks (Q4W), tafolecimab 600 mg every 6 weeks (Q6W), placebo Q4W or placebo Q6W for 48 weeks. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Secondary endpoints included proportion of patients achieving ≥50% LDL-C reductions, LDL-C <1.8 mmol/L and LDL-C <1.4 mmol/L. Results: A total of 618 patients (mean LDL-C level 2.85 mmol/L; 9.3% on ezetimibe; 72.8% at very-high cardiovascular risk) were randomized. Of 614 patients receiving at least one dose of the study treatment, 568 (92.5%) completed the study. At both dose regimens, tafolecimab treatment induced significant reductions in LDL-C levels, and significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L and LDL-C <1.4 mmol/L compared with corresponding placebo groups ( Table ). Meanwhile, significant reductions in non-high density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) levels were achieved with tafolecimab versus placebo at week 48. The most commonly-reported treatment-emergent adverse events were upper respiratory tract infection, urinary tract infection and hyperuricemia. Conclusions: Tafolecimab administered at either 450 mg Q4W or 600 mg Q6W yielded significant and durable reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with non-familial hypercholesterolemia.
To assess the effect of short-term continuous positive airway pressure (CPAP) upon 24 h glucose control via a continuous glucose monitoring system (CGMS) in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes (OWD).Eleven cases of hospitalized OWD with age 43 - 70 (56 +/- 10) years old, body mass index 22.3 - 38.3 (28.5 +/- 5.5) kg/m(2) and apnea hypopnea index (AHI) 12 - 68 (45 +/- 23) times/h was recruited. CGMS was applied 2 days before and 4 days during CPAP treatment. The 24 h, treatment hours (6 h, 0:00-6:00) and non- treatment hours (18 h) glucose level and glucose variability were analyzed. Insulin resistance was assessed with fasting plasma blood glucose (FBG), plasma insulin (FINS) and homeostatic model assessment of insulin resistance index (HOMA-IR).Short-term CPAP treatment corrected sleep disordered breathing, and induced significant decreases of 24 h and treatment hours blood glucose level [(7.97 +/- 1.31) vs (7.52 +/- 0.94) mmol/L, (7.24 +/- 1.51) vs (6.77 +/- 1.65) mmol/L, both P < 0.05). Glucose variability of 24 h and treatment hours and non-treatment hours significantly decreased after CPAP treatment (1.22 +/- 0.34 vs 0.89 +/- 0.28, 0.43 +/- 0.24 vs 0.31 +/- 0.18, 1.23 +/- 0.89 vs 0.49 +/- 0.26, all P < 0.05). Short-term treatment also induced increase of insulin sensitivity, as indicated by a significant decrease of HOMA-IR (3.65 +/- 1.93 vs 2.79 +/- 1.68, P < 0.05).Short-term CPAP treatment in OWD may have an improving effect not only upon insulin resistance but also upon whole-day blood glucose and glucose variability.
The study aimed at assessing glucose control measured with a continuous glucose monitoring system (CGMS) before and after short-term continuous positive airway pressure (CPAP).Twenty-four type 2 diabetic patients (T2DM) with Obstructive sleep apnea syndrome (OSAS) (mean age 55.0 ± 9.0 years; BMI 29.5 ± 5.2 kg/m2) were admitted and kept under diet control for 2 days, then underwent 2 overnight polysomnographies: a diagnostic study and one with CPAP titration. Then they were treated by CPAP during sleep for the following three nights. Participants were divided into subgroup D (only diet control) and subgroup M (with DM medication). CGMS was utilized over the last five days. Glucose control was also assessed with plasma insulin and a clinical measure of insulin resistance (HOMA-IR) index.The mean (±SD) apnea-hypopnea index (AHI) at diagnostic polysomnography was 51.2 ± 22.4 (range 10-88) events/h. CPAP treatment in the subjects with OSAS resulted in the index of oxygenation desaturations being reduced from 33.3 ± 20.1 to 1.1 ± 1.6 (P =0.00). CGMS showed mean 24-hours glucose values significantly lower after CPAP treatment than at baseline in both subgroups (7.97±1.31 vs 7.52±0.94, P=0.033 in subgroup D; and 7.72±1.51 vs 7.17±1.21, P=0.05 in subgroup M), as the fasting plasma insulin levels and HOMA-IR were also decreased significantly after CPAP treatment (13.0 ± 7.5μU/mL vs 10.8 ± 5.4μU/mL, P=0.044; and 4.2 ± 2.2 vs 3.1±1.7, P=0.003, respectively). Standard deviation (SD) and mean amplitude of glucose excursions (MAGE) were also decreased in the subgroup D (1.91 ± 1.10 vs 1.61 ± 1.20, P=0.014; 1.26 ± 1.13 vs 1.01 ± 0.98, P=0.008, respectively) only.Short-term CPAP treatment in OSAS with type 2 diabetic patients is accompanied by a decrease in blood glucose level and improved insulin sensitivity. Glucose variability was reduced but only in the patients with diet control.
Kleine-Levin syndrome (KLS) is a rare disorder of relapsing sleepiness. The hypothesis was that the syndrome is related to a change in the vigilance peptide orexin A.From 2002 to 2013, 57 patients with relapsing hypersomnolence were clinically assessed in a referral academic center in Beijing, China, and 44 (28 males and 16 females; mean age 18.3 ± 8.9 y (mean ± standard deviation, range 9-57 y) were determined to have clinical and behavioral criteria consistent with KLS. Cerebrospinal fluid orexin A levels and diurnal blood pressure were measured in relapse versus remission in a subgroup of patients.Presenting symptoms included relapsing or remitting excessive sleepiness-associated parallel complaints of cognitive changes (82%), eating disorders (84%); depression (45%); irritability (36%); hypersexuality (18%); and compulsions (11%). Episodes were 8.2 ± 3.3 days in duration. In relapse, diurnal values for blood pressure and heart rate were lower (P < 0.001). In a subgroup (n = 34), cerebrospinal fluid orexin A levels were ∼31% lower in a relapse versus remission (215.7 ± 81.5 versus 319.2 ± 95.92 pg/ml, P < 0.001); in three patients a pattern of lower levels during subsequent relapses was documented.There are lower orexin A levels in the symptomatic phase than in remission and a fall and rise in blood pressure and heart rate, suggesting a role for orexin dysregulation in KLS pathophysiology.
To evaluate the clinical value of transcutaneous carbon dioxide (TcPCO2) measurement during sleep respiratory monitoring.A total of 29 patients were prospectively recruited. Their age range was (49.5 ± 12.9) years and body mass index (BMI) (28.2 ± 3.6) kg/m(2). All of them underwent polysomnography (PSG) at Sleep Center, Peking University People's Hospital during the period of January-August 2013. TcPCO2 signal was entered into PSG systems and TcPCO2 (TCM4, Radiometer,Demark) measured simultaneously. Arterial blood gas (ABG) analysis for arterial pressure of CO2 (PaCO2) was undertaken to validate TcPCO2 measurement. The data were statistically analyzed by Pearson's product-moment correlation. Dynamic change of TcPCO2 was monitored during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. The effect of noninvasive positive airway pressure ventilation (NPPV) treatment on TcPCO2 during sleep was also observed.TcPCO2 (44.2 ± 4.0) mmHg (1 mmHg = 0.133 kPa) was highly correlated with PaCO2 (43.2 ± 4.7) mmHg (Pearson's correlation, r = 0.896, P = 0.000), TcPCO2 (45.8 ± 5.4) mmHg level during wakefulness correlated significantly with that during N1, N2, N3 and REM sleep stages (r = 0.658, 0.871, 0.898,0.775; P = 0.009, 0.000, 0.003, 0.000). TcPCO2 levels during different sleep stages were all higher than that of wakefulness.However, TcPCO2 levels did not differ between two sleep stages. During both NREM and REM, elevated TcPCO2 returned to the level during wakefulness on NPPV treatment.Continuous monitoring of PCO2 is well-tolerated during PSG testing. And the signal is stable. During whole night sleep, TcPCO2 monitoring provides more accurate and clinically acceptable estimation of PaCO2 so that it helps to titrate the NPPV pressure levels.
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