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.

Objective: To investigate the association of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin, so as to provide scientific evidence for childhood obesity prevention and intervention measures in the population. Methods: From January 2022 to June 2024, 296 children and adolescents with intellectual disabilities and autism spectrum disorders aged 2-18 years were recruited from special education schools and institutions in Tianjin. Height and weight were measured, and a standardized questionnaire was used to assess physical activity and screen time. Binary Logistic regression analysis was carried out to investigate the association of physical activity and screen time with overweight and obesity. Results: The prevalence of overweight and obesity among children and adolescents with special needs in Tianjin were 17.2% and 21.6%, respectively, and the combined prevalence of overweight and obesity was 38.9%. The median of moderatetovigorous physical activity (MVPA) time was 0.20 h/d, and physical activity sufficiency rate was 7.8%. The median of screen time was 1.79 h/d, and the screen time compliance rate was 68.2%. The binary Logistic regression results showed that lower levels of MVPA time and increased screen time were associated with a higher risk of overweight and obesity among children and adolescents with special needs [OR(95%CI)=1.80(1.06-3.07), 2.40(1.42-4.07),P<0.05]. Conclusions Insufficient physical activity and excessive screen time are associated with an increased risk of overweight and obesity among children and adolescents with special needs. Therefore, comprehensive intervention measures should be implemented as early as possible to prevent and reduce the incidence of overweight and obesity in this population.

Objective     To evaluate the clinical effectiveness of valve-sparing aortic root replacement (VSARR) in the treatment of patients with dilated aortic root after operation for tetralogy of Fallot (TOF). Methods     A retrospective analysis was conducted on clinical data of TOF patients with aortic root dilation who underwent VSARR in our hospital from 2016 to 2022. Results     Finally 14 patients were collected, including 8 males and 6 females, with a median age of 22 years ranging from 12-48 years. Among them, 5 patients had severe aortic valve regurgitation, 4 moderate regurgitation, and 5 mild or no regurgitation. Six patients had sinus of valsalva dilation, and 8 significant dilation of the ascending aorta. One patient had residual shunt due to ventricular septal defect, and 9 severe pulmonary valve regurgitation. The David procedure was performed in 10 patients, Yacoub procedure in 2 patients, and Florida sleeve in 2 patients. There was no perioperative mortality in the group. The median follow-up time was 2.9 years (ranging from 0.4 to 6.0 years). One patient had mild aortic valve regurgitation, and the rest had minimal or no regurgitation. One patient had mild stenosis of the left ventricular outflow tract, and the rest patients had no obvious stenosis. Conclusion     VSARR is a satisfactory treatment for aortic root dilation in patients with TOF, with no significant increase in the incidence of left ventricular outflow tract stenosis or aortic regurgitation during mid-term follow-up.

Objective To establish an indirect enzyme-linked immunosorbent assay(ELISA)method for testing the concentration of a monoclonal antibody target tumor necrosis factor-α(TNF-α)in animal serum.Methods The critical parameters of the method including coating concentration of human TNF-α,source,concentration and stability of HRP-labeled goat anti-human immunoglobulin G(IgG)were investigated.The specificity,accuracy,precision,linearity and Limited of Determination of the method were investigated.Results The critical parameters of the method were confirmed as below:TNF-α was coated at 400 ng·mL-1;HRP labeled goat anti-human IgG antibody was diluted at 1:3.0 ×105;the diluted horseradish peroxidase labeled goat anti-human IgG antibody is well stored at 4 ℃ for 3 days.Meanwhile the method was confirmed to have good specificity,the recovery rate ranged from 84.00％to 106.82％,the coefficient of variation of different antibody concentration levels were no more than 10％;the method had a good linearity and the standard curve was y=(-8.37×103-2.37 × 106)/[1+(x/29.80)106]+2.37 × 106(R2=0.999);the limit of quantification was 1 ng·mL-1,all of which met the requirements.Conclusion A accurate and robust ELISA method was developed to test the concentration of anti-TNF-α monoclonal antibody in serum.

Objective To investigate the molecular mechanism of action of isoglycoside-4'-O-apigenin(1 → 2)glucoside(licraside)intervention in alleviating cholestasis.Methods Farnesol X receptor(FXR)was silenced in human HepG2 cells using lentivirus,and bilirubin and α-isothiocyanate(ANIT)were used to induce HepG2 cells to construct a hypercholate-hyperbilirubin model.The effects of licraside on cell viability,biochemical indices contents and the expression level of FXR and its downstream related proteins in the model were investigated.HepG2 cells and FXR-silenced HepG2 cells were divided into normal,model and experimental groups.Bilirubin and probenecid were added to all groups except the normal group,and 80 μmol·L-1 licraside was added to the experimental group.After 24 h of culture,cell viability and the levels of total bile acids(TBA),bilirubin and other biochemical indices were examined in each group;the protein expression levels of FXR and bile salt efflux pump(BSEP)were examined in each group by Western blot assay.Results The cell viability in HepG2 cells normal group,HepG2 cells model group,HepG2 cells experimental group,siFXR-HepG2 cells normal group,siFXR-HepG2 cells model group and siFXR-HepG2 cells experimental group were(100.00±17.15)％,(39.41±2.91)％,(70.79±3.74)％,(81.41±5.12)％,(33.49±2.69)％and(44.08±4.82)％;the levels of TBA were(7.98±5.87),(46.18±10.93),(9.25±7.20),(11.18±3.36),(38.28±5.12)and(34.79±5.39)μmol·L-1;the levels of total bilirubin were(5.21±3.27),(40.29±24.88),(5.21±2.64),(12.00±4.64),(56.36±14.85)and(15.39±5.56)μmol·L-1;the relative expression levels of FXR protein were 1.00±0.10,0.81±0.07,1.11±0.09,0.10±0.02,0.12±0.02 and 0.10±0.04;the relative expression levels of BSEP protein were 1.00±0.17,0.81±0.02,0.88±0.03,0.70±0.09,0.49±0.07 and 0.60±0.10.The differences of the above indexes in the HepG2 cells experimental group compared with the model group were statistically significant(P＜0.001,P＜0.01);except for TBA,the differences of the above indexes in siFXR-HepG2 cells experimental group compared with the model group were statistically significant(P＜0.001,P＜0.01).Conclusion Licraside can effectively reduce the biochemical indices level of hypercholate-hyperbilirubin cell model.This effect is achieved by agonizing of FXR protein expression,increase the efflux of bile acid salt and then reduce the synthesis of bile acids,and eventually achieve the effect of alleviating the cholestasis.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

【Objective】 To analyze the serological characteristics and molecular mechanism of a novel B subtype allele 803delC. 【Methods】 ABO blood group was detected by serological method. Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to detect ABO blood group genes. The coding region of exon 1-7 of ABO gene was detected by Sanger sequencing to determine the mutation site. 【Results】 Serological identification of patients was with forward O-type and reverse B-type. The result of PCR-SSP genotyping was A/O. There was A gene, which was not consistent with serological results. Further Sanger double-strand sequencing revealed that the C-base was deleted at position 803 of exon 7 on the basis of ABO^*B. 01/ABO^*O. 01.01. The mutation eventually leads to the amino acid substitution of p. Ala268Gly and p. Phe269Ser and the production of new open reading frame starting at position 269, with the new open reading frame No.20 amino acid being stop codon, resulted in the termination of B gene expression. Further single-strand sequencing of the ABO gene revealed that the mutation was located in the ABO^*B. 01 gene. The mutation was submitted to the NCBI database with the number OR343908. 【Conclusion】 A new ABO allele leading to B variant has been found in Chinese population. Genetic detection can be used to identify the ambiguous blood group with discrepancy between forward and reverse blood grouping.

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.