[Advances in the detection of arousal in obstructive sleep apnea].

Obstructive sleep apnea (OSA) is primarily characterized by intermittent nocturnal hypoxia and sleep fragmentation. Arousals interrupt sleep continuity and lead to sleep fragmentation, which can lead to cognitive dysfunction, excessive daytime sleepiness, and adverse cardiovascular outcome events, making arousals important for diagnosing OSA and reducing the risk of complications, including heart disease and cognitive impairment. Traditional arousal interpretation requires sleep specialists to manually score PSG recordings throughout the night, which is time consuming and has low inter-specialist agreement, so the search for simple, efficient, and reliable arousal detection methods can be a powerful tool to clinicians. In this paper, we systematically reviewed different methods for recognizing arousal in OSA patients, including autonomic markers (pulse conduction time, pulse wave amplitude, peripheral arterial tone, heart rate, etc.) and machine learning-based automated arousal detection systems, and found that autonomic markers may be more beneficial in certain subgroups, and that deep artificial networks will remain the main research method for automated arousal detection in the future.

[Prediction models for respiratory event types in OSA patients based on hypoxic parameters].

Objective: To analyze the hypoxic parameters in patients with obstructive sleep apnea (OSA), to explore the difference and association between different types of respiratory events and to construct predictive models for respiratory event types. Methods: Fifty patients [including 41 males and 9 females with age 18-74(45.72±13.39) years ] with OSA diagnosed by polysomnography (PSG) were selected for retrospective analysis, and all respiratory events with pulse oximetry (SpO2) desaturation in the recorded overnight data were divided into hypopnea group (Hyp, 3 316), obstructive apnea group (OA, 5 552), central apnea group (CA, 1 088) and mixed apnea group (MA, 1 369) according to the type of events, and all event records were exported separately from the PSG software as comma-separated variable (.csv) files, which were imported and analyzed using the in-house built Matlab software. A total of 13 hypoxic parameter differences were compared among the four groups, including minimum oxygen saturation of events (e-minSpO2), the depth of desaturation (ΔSpO2), the duration of desaturation and resaturation (DSpO2), the duration of desaturation (d.DSpO2), duration of resaturation (r.DSpO2), duration of SpO2<90% (T90), duration of SpO2<90% during desaturation (d.T90), duration of SpO2<90% during resaturation (r.T90), area under the curve of SpO2<90% (ST90), area under the curve of SpO2<90% during desaturation (d.ST90), area under the curve of SpO2<90% during resaturation (r.ST90), oxygen desaturation rate (ODR) and oxygen resaturation rate (ORR). Hyp model (H), OA model (O), CA model (C) and MA model (M) were constructed respectively; group differences for the different hypoxia parameters were assessed using single factor analysis and Kruskal-Wallis H test. For different categories of respiratory events, binary logistic regression was used to identify the variables included in the regression model. Receiver operating characteristic (ROC) curves were generated to assess and compare the sensitivity, specificity, positive predictive value and negative predictive value of the four models, thereby gauging the predictive precision of each model. Results: ΔSpO2, ODR, ORR, T90, d.T90, r.T90, ST90, d.ST90 and r.ST90 for each type of respiratory events showed MA>OA>CA>Hyp, and e-minSpO2 showed MA

A versatile control program for positioning and shooting targets in laser-plasma experiments.

We introduce a LabVIEW-based control program that significantly improves the efficiency and flexibility in positioning and shooting solid targets in laser-plasma experiments. The hardware driven by this program incorporates a target positioning subsystem and an imaging subsystem, which enables us to install up to 400 targets for one experimental campaign and precisely adjust them in six freedom degrees. The overall architecture and the working modes of the control program are demonstrated in detail. In addition, we characterized the distributions of target positions of every target holder and simultaneously saved the target images, resulting in a large dataset that can be used to train machine learning models and develop image recognition algorithms. This versatile control system has become an indispensable platform when preparing and conducting laser-plasma experiments.

[Relationship between respiratory event-related arousal and increased pulse rate in patients with obstructive sleep apnea].

Objective: To investigate the relationship between respiratory event-related arousal and increased pulse rate in patients with obstructive sleep apnea (OSA), and to evaluate whether elevated pulse rate can be used as a surrogate marker of arousal. Methods: A total of 80 patients [40 males and 40 females, age range (18-63 years), mean age (37±13) years] who attended the Sleep Center of the Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital for polysomnography (PSG) from January 2021 to August 2022 were enrolled. Stable PSG recordings of non-rapid eye movement (NREM) sleep to compare the mean pulse rate (PR), the lowest PR 10 seconds before the onset of arousal, and the highest PR within 10 seconds after the end of arousal associated with each respiratory event. At the same time, the correlation between the arousal index and the pulse rate increase index (PRRI), as well as ΔPR1 (highest PR-lowest PR) and ΔPR2 (highest PR-mean PR), respectively, with the duration of respiratory events, the duration of arousal, the magnitude of pulse oximetry (SpO2) decline, and the lowest SpO2 was analyzed. Among the 53 patients, 10 events without arousal and 10 events with arousal (matched for the magnitude of SpO2 decline) were selected for NREM in each of the 53 patients, and ΔPR before and after termination of respiratory events in the two groups was compared. In addition, 50 patients were simultaneously subjected to portable sleep monitoring (PM) and divided into non-severe OSA group (n=22) and severe OSA group (n=28), and ΔPR≥3 times,≥6 times,≥9 times, and≥12 times after respiratory events were used as surrogate markers of arousal, and ΔPR was scored manually and integrated into the respiratory event index (REI) of PM. Then, we compared the agreement between REI calculated from the four PR cut-off points and the apnea-hypopnea index (AHIPSG) calculated by the gold standard PSG. Results: ΔPR1 [(13±7)times/min] and ΔPR2 [(11±6)times/min] were significantly higher in patients with severe OSA than in patients with non-OSA,mild and moderate OSA. The arousal index was positively correlated with the four PRRIs (r 0.968, 0.886, 0.773, 0.687, P<0.001, respectively), and the highest PR [(77±12) times/min] within 10 s after the end of arousal was significantly higher than the lowest PR [(65±10) times/min, t=113.24, P<0.001] and the mean PR [(67±11) times/min, t=103.02, P<0.001]. ΔPR1 and ΔPR2 were moderately correlated with the decrease in SpO2 (r=0.490, 0.469, P<0.001). After matching the magnitude of SpO2 decline, the ΔPR[(9±6)/min] before and after the termination of respiratory events with arousal was significantly higher than that of respiratory events without arousal [(6±5)/min, t=7.72, P<0.001]. The differences between REI+PRRI3 and REI+PRRI6 and AHIPSG in the non-severe OSA group were not statistically significant (P values 0.055 and 0.442, respectively), and REI+PRRI6 and AHIPSG showed good agreement (the mean difference was 0.7 times/h, 95%CI 8.3-7.0 times/h). The four indicators of PM in the severe OSA group were statistically different from AHIPSG (all P<0.05), and the agreement was poor. Conclusions: Respiratory event-related arousal in OSA patients is independently associated with increased PR, and frequent arousal may lead to increased frequency of PR fluctuations, and elevated PR may be used as a surrogate marker of arousal, especially in patients with non-severe OSA, where elevated PR≥6 times significantly improves the diagnostic agreement between PM and PSG.

[The effect of large-conductance calcium-activated potassium channels on the migration of pericytes in the mice of senile cochlear stria vascularis].

Objective: To investigate whether large conductance calcium-activated potassium channel (BK(Ca)) was involved in the migration of pericytes (PC) in the mice of senile cochlear stria vascularis capillaries PC. Methods: C57BL/6J mice were divided into 3-month (n=10) and 12-month groups (n=10). Auditory brainstem response (ABR) was used to test the hearing threshold of each group. The immunofluorescence was used to detect the expression changes of osteopontin (OPN) and ß-BK(Ca) channels on cochlear stria vascularis PC. The morphological changes of perivascular cells in cochlea were observed by transmission electron microscope (TEM). Cell experiment: The PC, which were in the stria vascularis of the cochlea were primary cultured and identified. A cell senile model was made with D-gal. The appropriate intervention concentration of low galactose (D-gal) was determined by CCK8. ß-galactosidase (SA-ß-gal) staining was used to evaluate the cell decrept level. The change of BK(Ca) channels current on PC were recorded by whole cell patch clamp technique. The expression of BK(Ca) channels on PC was detected by immunofluorescence. The migration and invasion ability of two groups were detected by using Scratch test and Transwell. The levels of OPN and ß-BK(Ca) channels were detected by Western blot. SPSS 22.0 software was used to analyze the data. Results: The ABR threshold in the 12-month group was higher than 3-month group (t=12.66, P<0.01). In the 12-month group, the expression of ß-BK(Ca) channel was lower and the expression of OPN was increased (t=14.64, P<0.01; t=20.73, P<0.01). In TEM, cochlear stria vascularis PC were tightly connected to endothelial cells in 3-month group, while PC were loosely connected to endothelial cells or PC soma were separated from the capillary in 12-month group. Cell experiment: The positive rate of PC in the primary cultured cochlear stria vascularis is above 95%. Compared with the SA-ß-gal stained cells in the control group, the positive rate of 15 mg/ml D-gal intervention PC was 85% (t=36.90, P<0.01). Whole cell patch clamp BK(Ca) channels current decreased in the D-gal group compared with the young group PC (t=12.18, P<0.05). The OPN expression in the senile group was higher than control group (t=16.30, P<0.01), while the ß-BK(Ca) channels expression was decreased (t=11.98, P<0.01; t=15.72, P<0.05), and migration ability raised (t=7.91, P<0.01;t=7.59, P<0.01). After intervened of BK(Ca) channels specific blocker IBTX in the D-gal group, the expression of OPN and migration were increased (t=4.26, P<0.05; t=5.88, P<0.01; t=21.97, P<0.01). Conclusion: PC migration capacity were increased during the senile period, and the expression of ß-BK(Ca) channel was decreased. The administration of IBTX, a specific blocker of BK(Ca) channel, at the cell level could increase the migration capacity, suggesting that BK(Ca) might be involved in the migration of PC in the stria vascularis of the aging cochlea.

[Effect of microvascular pericytes of cochlear stria vascularis on endothelial cell permeability in C57BL/6J mice].

Objective: To study the changes in the permeability of the blood labyrinth barrier of the aging cochlea in mice, and to establish a non-contact co-culture model of endothelial cells (EC) and pericytes (PC) to furtherly investigate the cochlear stria vascularis microvascular pericytes impact on the permeability of endothelial cells. Methods: C57BL/6J mice were divided into two groups, three months old as young group, 12 months old as senile group. Cell experiment was divided into four groups, EC group, EC+PC co-culture group, D-gal+EC group and D-gal+EC+PC co-culture group. Auditory brainstem response (auditory brain response, ABR) was used to detect the auditory function of the two groups of mice. Evans blue staining was applied to detect the permeability of the cochlear blood labyrinth barrier of the two groups of mice. Transmission electron microscopy was used to observe the ultrastructure of blood labyrinth barrier endothelial cells, pericytes and tight junctions in the two groups of mice. Immunohistochemistry was used to detect the expression levels of tight junction proteins in the stria vascularis of the cochlea of the two groups of mice. Transwell chamber was used to detect the permeability of endothelial cells. Western blot and immunofluorescence technology were used to detect the expression level of tight junction protein on endothelial cells. SPSS 20.0 software was used to analyze the data. Results: Compared with the young group, the ABR threshold of the aging group was significantly increased, the latency of wave I was prolonged (t=10.25, P<0.01;t=5.61, P<0.05), the permeability of the cochlear blood labyrinth barrier was increased and the expression of tight junction protein on the vascular stria was decreased (P<0.05). The cochlear ultrastructure showed that the cochlear vascular stria microvascular lumen was deformed, the basement membrane thickened and the tight junction gap between endothelium enlarged. The positive rate of ECs and PCs in primary culture was more than 95%. The cells induced by 15 g/L D-gal were determined to be senescent cells. Compared with EC group, the expression of tight junction protein in endothelial cells of D-gal+EC group decreased（t=7.42，P<0.01；t=13.19，P<0.05）and the permeability increased (t=11.17, P<0.01). In the co-culture group, the expression of tight junction protein between endothelial cells in EC+PC co-culture group and D-gal+EC+PC co-culture group increased and the permeability decreased. Conclusions: In aging mice, the permeability of cochlear blood labyrinth barrier will increase and the level of tight junction protein will decrease; in aging state, cochlear vascular stria microvascular pericytes may affect endothelial cell permeability by regulating the expression of tight junction protein.

Shear-induced changes in endothelin-1 secretion of microvascular endothelial cells.

Human glomerular microvascular endothelial cell (HGMEC) culture monolayers were maintained in static culture as controls or subjected to steady laminar shear stress of 0.5, 1.0, or 1.5 N/m2. Over 25 h of shear, the cumulative secretion of ET-1 was 705.4 pg/cm2 in the control, 820.7 pg/cm2 at 0.5 N/m2, 1063.2 pg/cm2 at 1.0 N/m2, and 644.7 pg/cm2 at 1.5 N/m2. The average ET-1 secretion rate for the HGMEC monolayers exposed to 0.5, 1.0, or 1.5 N/m2 of shear stress was 32.83 +/- 2.01 pg/cm2 x h, 42.53 +/- 3.74 pg/cm2 x h, and 25.79 +/- 1.29 pg/cm2 x h, respectively. The average ET-1 secretion rate of the static controls was 28.22 +/- 3.11 pg/cm2 x h. The results showed that low shear stress (0.5 N/m2) elevated and high shear stress (1.5 N/m2) suppressed secretion of ET-1, while an intermediate level of shear stress (1.0 N/m2) led to the maximum secretion of ET-1, and furthermore, ET-1 secretion varied with the duration of shear in a nonlinear fashion, and the logistic equations may be used to describe relationship between the duration of shear and the ET-1 secretion. The major secretion period of ET-1 occurred between 5.3 and 22.3 h, with the peak secretion rate occurring at approximately 10.7-15.2 h. Our findings showed also that the major secretion period and peak secretion rate of HGMECs varied with the level of shear stress. Thus, the response of cultured human microvascular endothelial cells to shear stress differed from that of large-vessel endothelial cell cultures in terms of ET-1 secretion. In addition to the level of shear stress, the duration of shear is an important determinant in ET-1 secretion. Consequently, the heterogeneity of vascular endothelial cells and the duration of shear should both be considered in future research on the secretion of vascular endothelial cell cultures.

[Studies on the recurrent attacks of acute adenolymphangitis due to Malayan filariasis].

OBJECTIVE: To explore the role of filarial and bacterial infections in the recurrent attacks of acute adenolymphangitis due to malayan fialriasis. METHODS: 1. To observe the seasonal fluctuation of acute attacks by performing monthly follow-up on patients with history of acute attacks in recent years. 2. To study the relationship between bacterial infection and filarial adenolymphangitis by performing bacteria culture and anti-streptolysin O test. 3. To investigate the variation of acute attacks by controlling filariasis transmission or by treating patients with a history of recurrent acute attacks. RESULTS: 1. The peak of acute attacks in patients coincided with the peak of vector transmission season. 2. Of the 97 cases examined by bacteria culture, 90 cases were negative; of the 255 cases examined by anti-streptolysin O test, the titres in 94.1% (143/152) of the cases with first attack and simple adenolymphangitis were within normal limits, however, the titres in 27.2% (28/103) of the cases complicated with elephantiasis were increased. 3. The acute attack rate of adenolymphangitis per year reduced significantly in cases with first attack and simple adenolymphangitis after effective control of filariasis transmission. 4. There was no evidence of the reduction of acute attacks by treating patients with DEC alone. CONCLUSION: In malayan filariasis endemic areas, the main causes of recurrent attacks of acute adenolymphangitis might be the repeated filarial infections due to the persistence of filariasis transmission.

Correlative study on the expression of p53 and DNA ploidy in acute nonlymphocytic leukemia.

We used the flow cytometric immunoassay to study the correlation between the rumor-suppressor gene product p53- and the DNA ploidy in 30 de novo cases of acute nonlymphocytic leukemia (ANLL). The results showed that 15 cases were positive expression for p53. As compared with p53 negative (p53) cases, the patients with positive p53 (p53+) had higher percentage of bone marrow blasts and lower peripheral leukocyte and platelet counts, which had no influence on the complete remission rate. Before treatment, DNA diploidy was seen in 18 cases including 12 p53- cases, and DNA aneuploidy in 12 cases including 9 p53+. After therapy, aneuploidy could be transformed into diploidy. Patients with P53+ or having aneuploidy in complete remission were at risk for early relapse. We believe that p53 may be involved in the process of leukemogenesis and progression of ANLL.

Functional status of pancreatic islet in acute leukemia.

Using enzymatic assay and radioimmunoassay, we studied the functional status of pancreatic islet in 50 patients with acute leukemia. Oral glucose tolerance test and insulin and C peptide release were made in 40 patients before and after treatment. 14 patients who revealed diabetic curve and delayed insulin and C peptide release before treatment showed normal values in 6 after therapy. Five patients with impaired glucose tolerance and decreased insulin and C peptide release before treatment showed normalization of these parameters following therapy. Five patients with normal pretreatment values disclosed abnormal post-treatment results. The remaining 16 patients displayed normal results both before and after therapy. Anti-insulin antibodies were negative, and glucagon level was normal in all the 50 patients. The red cell insulin receptor binding rate analysed in 47 patients was significantly higher than in controls (P < 0.001). We considered that the disturbed glucose metabolism in acute leukemia was not uncommon mainly due to the dysfunction of pancreatic islet beta cells as a result of islet damage by leukemic cells, the effect of corticosteroid and chemotherapy and the preexisting diabetes. Impaired glucose metabolism had no influence on therapeutic effect.

Plasma ammonia in patients with acute leukemia.

Plasma ammonia level (PAL) was studied in 43 cases of acute leukemia (AL). PAL was 39.21 +/- 26.2 mumol/L in normal controls and 38.8 +/- 16.6 mumol/L in leukemic patients before chemotherapy. High PAL was found in 40 cases after chemotherapy. Six cases showed clinical manifestations due to severe hyperammonemia, including dizziness, lethargy, confusion, coma and mental changes of various degree, and there was also respiratory alkalosis. After ammonia-trapping therapy, 4 of the 5 patients recovered. The authors believe that high PAL is not uncommon after chemotherapy in leukemic patients. Respiratory alkalosis and unexplained mental and neurologic changes following intensive chemotherapy are useful clues for the diagnosis of hyperammonemia syndrome. Early diagnosis and treatment with ammonia-trapping may improve the rates of remission and survival.