OBJECTIVE This study investigated the clinical implications of endothelial cell-specific molecule 1(ESM-1)in obstructive sleep apnea(OSA)patients,with particular focus on its dynamic correlation with adhesion molecules,aiming to elucidate the regulatory role of ESM-1 in OSA-associated vascular endothelial impairment.METHODS This cross-sectional study enrolled participants undergoing polysomnography(PSG)at the Sleep Medicine Center of Beijing Anzhen Hospital,Capital Medical University between March 2017 and January 2018.Based on the inclusion criteria,161 participants were ultimately included and divided into OSA group(n=118)and control group(n=43).Demographic data and polysomnography parameters were collected.We used a powerful high-throughput Multiplex Immunobead Assay technology to simultaneously test plasm cytokines levels of ESM-1,inter-cellular adhesion molecule 1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1).Circulating C-reactive protein(CRP)and homocysteine(Hcy)were detected by routine blood chemistry panel.RESULTS Circulating ESM-1 levels were significantly elevated in patients with OSA compared with healthy controls[819.73(612.36-1393.47)pg/ml]vs.[286.17(114.48-513.81)pg/ml,P<0.001].After adjusting for confounding factors,we found that circulating ESM-1 levels were an independent risk factor for OSA(odds ratio=2.162,95%CI=1.522-3.072,P<0.001)and circulating ESM-1 levels were positively associated with ICAM-1 and VCAM-1 levels(β=1.977,95%CI=1.429-2.734,P<0.001).CONCLUSION Circulating ESM-1 levels were significantly increased in patients with OSA,which is closely related with adhesion molecules levels.ESM-1 may be a surrogate endothelial dysfunction marker and an independent risk factor for OSA.

Objective To construct and implement a swallowing disorder assessment and management program for tracheal intubated patients after extubation based on the 4R crisis management theory,providing standardized and scientific interventions for oral feeding.Methods Utilizing the expert meeting method with the 4R crisis management theory framework,a swallowing disorder assessment and management program was developed for post-extubation tracheal intubated patients.A convenience sampling method was employed to select patients with tracheal intubations treated from July to December 2023 in the emergency ICU,central ICU,and cardiovascular surgery ICU of a tertiary hospital in Zhejiang Province.The patients treated from October to December were assigned to an experimental group(n=68),while those treated from July to September were designated as a control group(n=58).The experimental group received the 4R crisis management-based intervention,whereas the control group received standard ICU assessment and management.Outcomes indicators included the incidence of post-extubation swallowing disorders,time to first oral intake,incidence of aspiration during initial feeding,nasogastric and nasointestinal tube placement duration,incidence of aspiration pneumonia during hospitalization,re-intubation rates,ICU readmission rates,ICU stay duration,and total hospitalization days.Results Of the initially recruited subjects,68 in the experimental group and 54 in the control group were included in the final analysis.After the intervention,the experimental group exhibited significantly lower rates of post-extubation swallowing disorders,shorter time to first liquid oral intake,aspiration incidence during first feeding,shorter durations of nasogastric and nasointestinal tube placement,aspiration pneumonia,ICU readmission compared to the control group(P＜0.05).No significant differences were observed between the groups in time to first regular oral intake,re-intubation rates(P＞0.05).Conclusion The risk management program for dysphagia following tracheal extubation based on the 4R crisis management theory is scientifically robust and safe,offering a valuable reference for clinical assessments and management of swallowing and eating post-extubation in tracheal intubated patients.

Objective To construct and implement a swallowing disorder assessment and management program for tracheal intubated patients after extubation based on the 4R crisis management theory,providing standardized and scientific interventions for oral feeding.Methods Utilizing the expert meeting method with the 4R crisis management theory framework,a swallowing disorder assessment and management program was developed for post-extubation tracheal intubated patients.A convenience sampling method was employed to select patients with tracheal intubations treated from July to December 2023 in the emergency ICU,central ICU,and cardiovascular surgery ICU of a tertiary hospital in Zhejiang Province.The patients treated from October to December were assigned to an experimental group(n=68),while those treated from July to September were designated as a control group(n=58).The experimental group received the 4R crisis management-based intervention,whereas the control group received standard ICU assessment and management.Outcomes indicators included the incidence of post-extubation swallowing disorders,time to first oral intake,incidence of aspiration during initial feeding,nasogastric and nasointestinal tube placement duration,incidence of aspiration pneumonia during hospitalization,re-intubation rates,ICU readmission rates,ICU stay duration,and total hospitalization days.Results Of the initially recruited subjects,68 in the experimental group and 54 in the control group were included in the final analysis.After the intervention,the experimental group exhibited significantly lower rates of post-extubation swallowing disorders,shorter time to first liquid oral intake,aspiration incidence during first feeding,shorter durations of nasogastric and nasointestinal tube placement,aspiration pneumonia,ICU readmission compared to the control group(P＜0.05).No significant differences were observed between the groups in time to first regular oral intake,re-intubation rates(P＞0.05).Conclusion The risk management program for dysphagia following tracheal extubation based on the 4R crisis management theory is scientifically robust and safe,offering a valuable reference for clinical assessments and management of swallowing and eating post-extubation in tracheal intubated patients.

Objective To investigate the role of high-temperature requirement factor A2(HTRA2)in the mitochondrial unfolded protein response(mtUPR)model induced by the neurotoxin 1-methyl-4-phenylpyridinium(MPP+)and the compensatory effects of other proteases.Methods The mtUPR cell model was established by treating SH-SY5Y cells with MPP+.Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay,and mitochondrial morphological changes and intracellular reactive oxygen species(ROS)levels were examined under transmission electron microscopy and fluorescence microscope,respectively.Western blot(WB)was used to detect the expression levels of C/EBP Homologous Protein(CHOP),Heat shock protein family E member 1(HSPE1),YME1-like 1 ATPase(YME1L1),Caseinolytic mitochondrial matrix peptidase proteolytic subunit(CLPP),and Lon peptidase 1,mitochondrial(LONP1).Lentivirus-mediated knockdown(KD)of the HTRA2 gene in SH-SY5Y cells was performed.The mRNA and protein expression levels of HTRA2 were detected by quantitative real-time polymerase chain reaction and WB,respectively.After induction of mtUPR in HTRA2-KD SH-SY5Y cells with 400 μmol/L MPP?,cell viability and protein expression levels of HTRA2,YME1L1,CLPP,and LONP were evaluated using the CCK-8 assay and WB,respectively.Results mtUPR cell model was successfully established following treatment of SH-SY5Y cells with 400 μmol/L MPP+for 24 hours.Compared to the control group,there was no significant change in cell viability.Under electron microscopy,there were no remarkable alterations in the mitochondrial cristae and size in the mtUPR group.The average fluorescence intensity of ROS in the mtUPR group was 1.25±0.08 fold that of the PBS group,and the difference was statistically significant(P=0.001).The expression levels of CHOP,HSPE1,HTRA2,CLPP,and LONP were significantly higher in the mtUPR group than in the control group,which were 2.68±0.94、2.83±0.89、1.67±0.20,1.65±0.28,and 1.66±0.13 times that of control group,respectively(all P<0.05).The expression level of YME1L1 in the mtUPR group was 1.28±0.27 times that of the control group,with no statistical significance(P>0.05).After knockdown of the HTRA2 gene in SH-SY5Y cells,the expression levels of CLPP,YME1L1,and LONP1 increased to 1.46±0.79,1.41±0.12,and 1.32±0.25 times that of the empty virus group,respectively(all P<0.05).Following treatment with 400 μmol/L MPP+for 24 hours in HTRA2-KD SH-SY5Y cells,cell viability in HTRA2-KD group decreased to 88.4%±6.1%of the empty virus group(P<0.05).In the HTRA2 group,there were no significant changes in the expression levels of YME1L1 and LONP1 compared to the empty virus group(all P>0.05),while the expression level of CLPP increased to(1.88±0.62)times that of the empty virus group(P=0.033).Conclusion HTRA2 is an important mitochondrial protease in the MPP+-induced mtUPR response,and other mitochondrial proteases partially compensate for the function of HTRA2.

Objective To investigate the role of high-temperature requirement factor A2(HTRA2)in the mitochondrial unfolded protein response(mtUPR)model induced by the neurotoxin 1-methyl-4-phenylpyridinium(MPP+)and the compensatory effects of other proteases.Methods The mtUPR cell model was established by treating SH-SY5Y cells with MPP+.Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay,and mitochondrial morphological changes and intracellular reactive oxygen species(ROS)levels were examined under transmission electron microscopy and fluorescence microscope,respectively.Western blot(WB)was used to detect the expression levels of C/EBP Homologous Protein(CHOP),Heat shock protein family E member 1(HSPE1),YME1-like 1 ATPase(YME1L1),Caseinolytic mitochondrial matrix peptidase proteolytic subunit(CLPP),and Lon peptidase 1,mitochondrial(LONP1).Lentivirus-mediated knockdown(KD)of the HTRA2 gene in SH-SY5Y cells was performed.The mRNA and protein expression levels of HTRA2 were detected by quantitative real-time polymerase chain reaction and WB,respectively.After induction of mtUPR in HTRA2-KD SH-SY5Y cells with 400 μmol/L MPP?,cell viability and protein expression levels of HTRA2,YME1L1,CLPP,and LONP were evaluated using the CCK-8 assay and WB,respectively.Results mtUPR cell model was successfully established following treatment of SH-SY5Y cells with 400 μmol/L MPP+for 24 hours.Compared to the control group,there was no significant change in cell viability.Under electron microscopy,there were no remarkable alterations in the mitochondrial cristae and size in the mtUPR group.The average fluorescence intensity of ROS in the mtUPR group was 1.25±0.08 fold that of the PBS group,and the difference was statistically significant(P=0.001).The expression levels of CHOP,HSPE1,HTRA2,CLPP,and LONP were significantly higher in the mtUPR group than in the control group,which were 2.68±0.94、2.83±0.89、1.67±0.20,1.65±0.28,and 1.66±0.13 times that of control group,respectively(all P<0.05).The expression level of YME1L1 in the mtUPR group was 1.28±0.27 times that of the control group,with no statistical significance(P>0.05).After knockdown of the HTRA2 gene in SH-SY5Y cells,the expression levels of CLPP,YME1L1,and LONP1 increased to 1.46±0.79,1.41±0.12,and 1.32±0.25 times that of the empty virus group,respectively(all P<0.05).Following treatment with 400 μmol/L MPP+for 24 hours in HTRA2-KD SH-SY5Y cells,cell viability in HTRA2-KD group decreased to 88.4%±6.1%of the empty virus group(P<0.05).In the HTRA2 group,there were no significant changes in the expression levels of YME1L1 and LONP1 compared to the empty virus group(all P>0.05),while the expression level of CLPP increased to(1.88±0.62)times that of the empty virus group(P=0.033).Conclusion HTRA2 is an important mitochondrial protease in the MPP+-induced mtUPR response,and other mitochondrial proteases partially compensate for the function of HTRA2.

Objective:To improve the method for the determination of related substances in vidarabine monophos-phate.Methods:The analysis was performed on an ChromCore AQC18 column(4.6 mm × 150 mm,5 μm)with mobile phase A of an aqueous solution containing 0.01 mol·L-1 tetrabutylammonium hydroxide and 0.1 mol·L-1 potassium dihydrogen phosphate and mobile phase B of methanol by gradient elution at the flow rate of 1.0 mL·min-1.The column temperature was maintained at 30 ℃ and the UV detection wavelength was set at 258 nm.Results:Related substances were effectively separated from the principal component.Vidarabine mono-phosphate and its four impurities showed a good linear relationship in the self-concentration ranges(r＞0.999 9).The average recoveries and were 95.0％-99.2％with RSDs(n=9)of 1.0％-4.4％related substances in vidar-abine monophosphate and 91.8％-102.1％with RSDs of 0.5％-4.8％(n=9)for vidarabine monophosphate for injection,respectively.Conclusion:The improved method is simple,rapid and specific,and can be used for the determination of related substances in vidarabine monophosphate.

Transcriptional phenotypic drug discovery has achieved great success,and various com-pound perturbation-based data resources,such as connectivity map(CMap)and library of inte-grated network-based cellular signatures(LINCS),have been presented.Computational strategies fully mining these resources for phenotypic drug discovery have been proposed.Among them,the fundamental issue is to define the proper similarity between transcriptional profiles.Tra-ditionally,such similarity has been defined in an unsupervised way.However,due to the high dimensionality and the existence of high noise in high-throughput data,similarity defined in the tra-ditional way lacks robustness and has limited performance.To this end,we present DrSim,which is a learning-based framework that automatically infers similarity rather than defining it.We evalu-ated DrSim on publicly available in vitro and in vivo datasets in drug annotation and repositioning.The results indicated that DrSim outperforms the existing methods.In conclusion,by learning tran-scriptional similarity,DrSim facilitates the broad utility of high-throughput transcriptional pertur-bation data for phenotypic drug discovery.The source code and manual of DrSim are available at https://github.com/bm2-lab/DrSim/.

Many pathogenic genes have been identified in early-onset Parkinson′s disease, but the early-onset Parkinson′s disease with 22q11.2 deletion has not been reported in Chinese. A case of early-onset Parkinson′s disease with 22q11.2 deletion was confirmed by whole-exome sequencing-based copy number variation detection in Fujian Medical University Union Hospital. This article reports its clinical characteristics and discusses its pathogenesis, diagnosis and treatment management.

Objective:To investigate the effects of different concentrations of hydrogen peroxide (H 2O 2) on the expression of histone deacetylase-2(HDAC-2) and mitogen activated protein kinases phosphatases-1(MKP-1) in A549 cells. Methods:The experimental models of A549 cells were established by intervening of different concentrations of H 2O 2(0, 100, 200, 400, 600, 800 μmol/L)for 2 h, 4 h, 8 h, 12 h and 24 h, respectively.The survival rate of A549 cells was detected by thiazolyl blue(MTT) assay, and the apoptosis of A549 cells was tested by lactic dehydrogenase(LDH) assay.The expression of HDAC-2 and MKP-1 protein was detected by Western blot. Results:(1)MTT results showed that compared with the control group (H 2O 2 was 0 μmol/L), the survival rate of A549 cells was decreased with the increase of H 2O 2 concentration at 2 h, 4 h, 8 h, 12 h, 24 h and 48 h. (2)LDH results showed that, compared with the control group, the inhibition rate of A549 cells increased with the increase of H 2O 2 concentration at 2 h, 4 h, 8 h, 12 h, 24 h and 48 h. (3)The expression of HDAC-2 protein decreased ( F=14.588, P<0.01), and the expression of MKP-1 protein increased ( F=64.297, P<0.01) in a concentration-dependent manner with the increase of H 2O 2 concentration at 12 h after H 2O 2 treatment. Conclusions:H 2O 2 participates in oxidative stress injury of lung cells by regulating the expression of HDAC-2 and MKP-1.

Objective:To evaluate the effect of peer education on improving compliance of cardiac rehabilitation in patients with coronary heart disease.Methods:Totally 64 patients were randomly divided into two groups, namely, the experimental group and the control group with 32 cases in each group. Patients in the experimental group received routine education, nursing, and rehabilitation, plus the peer education treatment, whereas the control group only received routine treatment. The time lasts for 6 months. The compliance of cardiac rehabilitation and the score of China Questionnaire of Quality of Life in Patients with Cardiovascular Diseases (CQQC) were measured after 1 month, 3month and 6 month.Results:After 1, 3, and 6 months of intervention, the compliance of cardiac rehabilitation in the intervention group increased by 18.75%, 21.37%, and 21.88%, respectively, compared with the control group. After the first and third months of intervention, there was a statistically significant difference in the compliance rate of rehabilitation exercise between the intervention group and the control group ( χ2 values were 18.050, 16.946, respectively, P <0.05), and at the sixth month after intervention, the compliance of the two groups of patients with cardiac rehabilitation was not statistically significant ( χ2 value was 6.489, P> 0.05). After 1, 3, and 6 months of intervention, the quality of life scores of the intervention group were (88.68 ± 6.65), (81.90 ± 6.78), and (76.33 ± 5.90) points, and the quality of life scores of the control group were (84.75 ± 4.72), (75.67 ± 5.88), and (74.71 ± 9.47) points. There was significant difference in the scores of the two groups in the first and third months after the intervention ( t values were 2.235, 2.520, respectively, P<0.05); and in the sixth month after the intervention, the difference in the scores of the two groups wasn`t statistically significant ( t value was 1.049, P >0.05). Conclusion:Peer education can improve the compliance of cardiac rehabilitation and the score of CQQC in patients with coronary heart disease in 3 month, but further research is needed to confirm the long-term effect of peer education.