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.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

Objective To observe the clinical efficacy and safety of ticagrelor tablets combined with atorvastatin calcium tablets in the treatment of cerebral thrombosis.Methods The patients with cerebral thrombosis were divided into control group and treatment group according to cohort methods.Two groups were given basic therapy.On the basic therapy,control group was given atorvastatin calcium 20 mg per time,once a day,orally;on the basic of control group,the treatment group received ticagrelor 90 mg per time,twice a day,orally.Two groups were treated for 4 months.The clinical efficacy,nerve function,blood viscosity,platelet parameters,brain injury markers and adverse drug reactions were compared between two groups.Results Treatment and control groups enrolled 119 and 117 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.60％(109 cases/119 cases)and 82.05％(96 cases/117 cases)with significant difference(P＜0.05).After treatment,the scale scores of treatment and control groups were(5.47±0.82)and(6.51±0.96)points;the plasma viscosity levels were(1.35±0.21)and(1.62±0.24)mPa·s,whole blood high shear viscosity levels were(3.67±0.51)and(4.01±0.59)mPa·s;the whole blood low shear viscosity levels were(6.12±0.93)and(7.05±1.07)mPa·s;the platelet adhesion rates were(30.52±3.81)％and(36.21±4.02)％;the mean platelet volumes were(12.75±1.86)and(15.42±2.06)fL;the carboxy-terminal hydrolase of ubiquitin levels were(0.39±0.06)and(0.51±0.07)μg·L-1;the key protein antigen-5 of aging levels were(90.76±12.23)and(81.64±11.95)μg·L-1;and the differences were statistically significant between two groups(all P＜0.05).The adverse drug reactions of two groups were nausea,vomiting,bleeding,abdominal pain and diarrhea.The total incidences of adverse drug reactions in treatment and control groups were 5.04％and 4.27％,without significant difference(P＞0.05).Conclusion Ticagrelor tablets combined with atorvastat in calcium tablets have a significant clinical efficacy in the treatment of patients with cerebral thrombus,which can significantly improve the neurological function,blood viscosity,brain injury markers,and platelet parameters of patients,without increasing the incidence of adverse drug reactions.

Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33％and 25.00％,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0～7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100％)and Pepsinogen Ⅰ(83％),focally positive for H+/K+-ATPase(58％).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.

OBJECTIVE To introduce a case of interstitial pneumonia induced by vedolizumab （VDZ）， summarize and analyze the characteristics of the occurrence of VDZ-associated lung toxicity， and provide a reference for the clinically safe use of drugs. METHODS From the perspective of clinical pharmacists， the diagnosis and treatment of a case of VDZ-induced interstitial pneumonia were retrospectively analyzed， and the association of adverse drug reactions （ADR） was analyzed. Retrieving from Chinese and English databases such as CNKI， VIP， PubMed and Web of Science， case reports of VDZ-associated lung toxicity were summarized and analyzed. RESULTS The patient developed interstitial pneumonia during the use of VDZ and empirical anti- infective therapy with antibiotics was ineffective. After withdrawal of VDZ and treatment with methylprednisolone， symptoms and imaging examinations improved， but interstitial pneumonia still existed. According to Naranjo’s ADR evaluation scale and based on China Adverse Drug Reaction Reporting and Monitoring Manual， the association between VDZ and interstitial pneumonia was “very likely”. Results of the literature analysis showed that among 29 involved patients （including the patient reported in this article）， there were 19 males and 10 females， with an average age of （49.24±17.06） years. Lung toxicity mainly included VDZ- associated pneumonia， eosinophilic pneumonia， pulmonary granulomas or necrobiotic nodules， interstitial lung injury， etc.， which mostly occurred ≤24 weeks after medication （58.62%）. The main clinical manifestations included cough， dyspnea and fever. The vast majority of patients improved or recovered after drug withdrawal and/or glucocorticoid treatment， but one patient died of respiratory failure. CONCLUSIONS Lung toxicity is a rare ADR of VDZ with insidious onset and nonspecific symptoms. Once patients experience symptoms such as cough and dyspnea， early diagnosis，timely drug withdrawal，and symptomatic treatment measures such as glucocorticoid should be taken to ensure medication safety.