1.Severity Assessment Parameters and Diagnostic Technologies of Obstructive Sleep Apnea
Zhuo-Zhi FU ; Ya-Cen WU ; Mei-Xi LI ; Ping-Ping YIN ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(1):147-161
Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO2 plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.
2.A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score, revised Geneva score, and Years algorithm
Linfeng XI ; Han KANG ; Mei DENG ; Wenqing XU ; Feiya XU ; Qian GAO ; Wanmu XIE ; Rongguo ZHANG ; Min LIU ; Zhenguo ZHAI ; Chen WANG
Chinese Medical Journal 2024;137(6):676-682
Background::Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods::This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Na?ve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis.Results::The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score ( P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726. Conclusions::Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.
3.Effects of low frequency repetitive transcranial magnetic stimulation at different stimulating sessions on upper limb motor function and brain functional connectivity in stroke patients
Yuan PENG ; Xi-Bin ZHANG ; Weiwen MEI
Chinese Journal of Rehabilitation Medicine 2024;39(10):1436-1442
Objective:To explore the effects of repeated transcranial magnetic stimulation(rTMS)at different stimulating sessions on upper limb motor function and brain functional connectivity in stroke patients,targeting on stimu-late the contralateral premotor cortex(PMC). Method:Sixty patients with upper limb motor dysfunction after ischemic stroke were randomly assigned to 6-week rTMS group,4-week rTMS group,2-week rTMS group or control group,each with 15 participants.Up-per limb Brunnstrom stage,Fugl-Meyer assessment for upper extremity(FMA-UE)and Wolf motor function test(WMFT)were assessed before and after treatment to evaluate behavioral outcomes.The functional connec-tivity was analyzed by resting state functional magnetic resonance imaging(rs-fMRI)with the contralateral PMC as the seed point. Result:After treatment,the FMA-UE and WMFT scores of the 2-week rTMS group were significantly differ-ent from those of the 4-week and 6-week rTMS groups(P<0.05),but there was no significant difference be-tween the 4-week rTMS group and the 6-week rTMS group(P>0.05).Functional connectivity analysis using contralateral PMC as a seed point showed that functional connections were enhanced between contralateral PMC and ipsilateral anterior central gyrus,as well as the contralateral middle temporal gyrus and precuneus af-ter rTMS treatment(P<0.05). Conclusion:The 4-week rTMS group has the best duration-benefit compared with the 2-week rTMS group and the 6-week rTMS group.The probable mechanism was related to that rTMS treatment could reduce the ef-fect of interhemispheric inhibition on motor cortex,and then enhance the cortico-cortical functional connectivi-ty in the contralateral hemisphere effectively,resulting in the recovery of upper limb motor function.
4.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.
5.Research Progress on the Roles of Rapamycin for the Prophylaxis and Treatment of Graft-Versus-Host Disease
Dan WANG ; Jing WEI ; Yi-Mei FENG ; Xi ZHANG
Journal of Experimental Hematology 2024;32(1):302-307
Graft-versus-host disease(GVHD)reduces the clinical effect and life quality of patients after allogeneic hematopoietic stem cell transplantation(HSCT).Especially for steroid-resistant GVHD,it becomes essential to explore new prevention and treatment strategies.Rapamycin has shown certain clinical advantages in the prevention and treatment of acute and chronic GVHD by inhibiting the mTOR signal pathway.Furthermore,rapamycin exhibits the ability to regulate cell subsets,including T cells,B cell,dendritic cells and myeloid-derived suppressor cells,which elucidates the mechanism on effective preventing and treating GVHD.This article reviewed the roles of mTOR inhibitor-rapamycin on GVHD,and discussed how to optimize the usage of rapamycin.
6.Analysis of RhC Antigen Weak Expression Combined with Mimicking Autoanti-Ce and Homologous Anti-Jkb Causing Mismatch
Hong-Mei YANG ; Xi YU ; Xin ZOU ; Si-Fei MA ; Jin CHEN ; Jian-Wei ZHANG
Journal of Experimental Hematology 2024;32(5):1539-1544
Objective:To investigate the reasons for the weak expression of RHCE gene in a patient whose mimicking anti-Ce combined with anti-Jkb caused cross-matching non-combination.Methods:ABO,Rh,and Kidd blood group antigens were identified by test tube method and capillary centrifugation.Antibody screening and antibody specificity identification were performed using saline,polybrene and antiglobulin in tri-media association with multispectral cells.RHCE gene sequencing and haploid analysis were performed by multiplex PCR technique and RHCE protein modeling was performed using Swiss-Model.Results:The serum of the patient contained anti-Ce mimicking autoantibodies along with anti-Jkb antibodies.c.48G>C,c.150C>T,c.178C>A,c.201A>G,c.203A>G,and c.307C>T mutations were detected in the RHCE triple-molecule sequencing.A 109 bp insertion sequence was found in intron 2,with fragment loss from intron 5-8.The Rh-group genotype was DCe/DCe,and phenotype was CCDee.Conclusion:Genotyping techniques can assist in deducing the molecular mechanisms of some weakly expressed RhC,c,E,and e in patients'sera to aid in the identification of difficult antibodies and thus ensure the safety of patients'blood transfusion.
7.Effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in a rat model of cardiac hypertrophy
Hao ZHANG ; Xiao-Yun DING ; Hu WANG ; Ting-Ting LI ; Yu-Mei QIU ; Meng-Die XIE ; Wei DONG ; Yi-Xin SHEN ; Xi-Lan TANG
Chinese Traditional Patent Medicine 2024;46(11):3594-3602
AIM To investigate the effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in isoproterenol(ISO)-induced rat heart tissue and primary myocardial cells of neonatal rats.METHODS The SD rats were randomly divided into the normal group,the model group,the Xinyue Capsules intervention group and Xinyue Capsules control group,with 8 rats in each group.The rat model of cardiac hypertrophy was established by 14 days consecutive intraperitoneal injection of ISO(30 mg/kg).Prior to the modeling,once daily administration of 0.393 g/kg Xinyue Capsules was given by gavage from 3 days in advance to the end of the experiment.After the last administration,the procurement of blood from abdominal aorta,the left and right ventricles were processed.And the rats had their indices levels of the heart,the left ventricle and the right ventricle measured;their pathomorphological changes of myocardial tissue observed using HE staining;their expressions of cardiac hypertrophy-related myocardial embryonic genes ANP,β-MHC and α-SKA mRNA detected using RT-qPCR method;and their serum TC,TG,LDL-C and HDL-C levels detected by biochemical method.In in vitro experiment,the neonatal rat model of myocardial hypertrophy was induced by exposure to ISO 1 μmol/L for 24 h.The investigation of the effect of Xinyue Capsules 12.5 μg/mL on ISO-induced myocardial hypertrophy was conducted by detection of myocardial cell area,embryo genes related to cardiac hypertrophy and myocardial cells protein cuntent.The further anti-cardiac hypertrophy mechanism of Xinyue Capsules research was conducted using RT-qPCR and Western blot to detect the gene and protein expressions of phospholipase A2(PLA2G6),phospholipase A1 member A(PLA1A)and lecithin cholesterol acyltransferase(LCAT)in left ventricle tissue and myocardial cells of each group.RESULTS The in vivo experimental result showed that compared with the normal group,the model group displayed increased indices levels of the heart,the left ventricle and the right ventricle and cross-sectional area of left ventricular myocytes(P<0.05);and up-regulated expressions of ANP,β-MHC,α-SKA mRNA and PLA2G6,PLA1A and LCAT mRNA and proteins in the left ventricle(P<0.05);and increased levels of serum TC,TG and LDL-C(P<0.05);and decreased HDL-C level(P<0.05).However,the intervention of Xinyue Capsules inhibited the changes of the aforementioned indices(P<0.05).The in vitro experimental result revealed that Xinyue Capsules inhibited the ISO-induced increases of myocardial cell surface area and myocardial cell protein level,the up-regulation of ANP,β-MHC,α-SKA mRNA expressions and the PLA2G6,PLA1A,LCAT mRNA and protein expressions as well(P<0.05).CONCLUSION Xinyue Capsules can improve the ISO-induced cardiac hypertrophy in rats,and its mechanism may be associated with its regulation upon the expressions of glycerophospholipid metabolism-related enzymes PLA2G6,PLA1A and LCAT.
8.Preliminary research of the therapeutic efficacy and safety of endoscopic ultrasound-guided selective varices devascularization for the treatment of esophagogastric varices (with video)
Zhihong WANG ; Chen SHI ; Zhuang ZENG ; Lihong CHEN ; Qianqian ZHANG ; Fumin ZHANG ; Xuecan MEI ; Xi WANG ; Derun KONG
Chinese Journal of Digestive Endoscopy 2024;41(7):543-549
Objective:To evaluate the efficacy and safety of endoscopic ultrasound-guided selective varices devascularization (EUS-SVD) for the treatment of esophagogastric varices.Methods:A total of 43 cases of liver cirrhosis with esophageal and gastric varices at the First Affiliated Hospital of Anhui Medical University from February to December 2021 were included in a retrospective cohort study. The cases were divided into two treatment groups based on endoscopic treatment: EUS-SVD group ( n=22) and conventional endoscopic sclerosant injection group (conventional gastroscopy group, n=21). The doses of sclerosants and tissue glue, effective rate of esophageal varice treatment within 2 months after surgery, rebleeding rate within 3 months after surgery, and adverse reactions were compared. Results:The differences in terms of mean patient age, gender composition, etiology of liver cirrhosis, Child-Pugh classification of liver function, classification of esophageal varices, composition of endoscopic treatment indications, and mean maximum diameter of gastric varices were not statistically significant between the two groups ( P>0.05), indicating the comparability of baseline data. Perforating veins outside the gastric wall of gastric varices could be detected during the procedure in the EUS-SVD group, and disappearance of gastric varices after injection treatment could be determined, while these two indicators could not be detected in the conventional gastroscopy group. The amounts of sclerosing agents and tissue adhesives used in the EUS-SVD group were 7.54±3.10 mL and 1.30±0.57 mL, respectively, while the corresponding amounts in the conventional gastroscopy group were 7.57±3.50 mL ( t=0.026, P=0.980) and 1.38±0.67 mL ( t=-0.452, P=0.654), respectively. The effective treatment rate for esophageal varice within 2 months after surgery was 63.6% (14/22) in the EUS-SVD group and 52.4% (11/21) in the conventional gastroscopy group, but the difference was not statistically significant ( χ2=0.559, P=0.455). The rebleeding rate within 3 months after surgery was 4.5% (1/22) in the EUS-SVD group, significantly lower than the rate of 33.3% (7/21) in the conventional gastroscopy group ( P=0.021). Neither group experienced events of ectopic embolism or death. There was no statistically significant difference between the two groups in terms of postoperative pain, fever, nausea and vomiting, or rebleeding rate within 72 hours after surgery ( P>0.05). The incidence of gastric fundus ulcers was 9.1% (2/22) in the EUS-SVD group, significantly lower than the rate of 42.9% (9/21) in the conventional gastroscopy group ( χ2=6.435, P=0.011). Conclusion:EUS-SVD treatment for esophagogastric varices is safe and effective. It can clearly display the deep-seated intramural vessels of the gastric wall, measure the diameter of the blood vessels, accurately inject tissue glue, occlude the varicose veins and perforating vessels, and reduce the occurrence of postoperative ulcers and rebleeding.
9.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
10. Function of Cortactin/N-cadherin signal axis in pathological myocardial hypertrophy
Yue-Mei WANG ; Wen-Jing YU ; Xi-Meng SUN ; Jing ZHANG ; Jing LU ; Pei-Qing LIU
Chinese Pharmacological Bulletin 2024;40(2):234-242
Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.

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