Objective To investigate the pharmacokinetics and relative bioavailability of praziquantel injection in buffaloes in contrast to praziquantel tablet. Methods A single oral administration of praziquantel tablet at a dose of 20 mg/kg or intramus-cular administration of praziquantel injection at a dose of 10 mg/kg was performed in six healthy adult buffalos according to a two-period crossover design. The praziquantel concentration in plasma was determined by a high performance liquid chromatography (HPLC)method. The pharmacokinetic parameters were calculated by non-compartmental analysis. Results The main pharma-cokinetic parameters of praziquantel tablet were as follows:Tmax=(0.60±0.29)h,Cmax=(0.57±0.37)μg/ml,T1/2β=(0.70±0.42) h,AUC=(0.80±0.70)(μg/ml)·h. The main pharmacokinetic parameters of praziquantel injection were as follows:Tmax=(0.65± 0.49)h,Cmax=(3.82 ± 1.17)μg/ml,T1/2β=(1.00 ± 0.73)h,AUC=(1.61 ± 0.89)(μg/ml)·h. The relative bioavailability of pra-ziquantel injection was 402.5％in contrast to praziquantel tablet. Conclusion The praziquantel injection has pharmacokinetic characteristics of rapid absorption,high bioavailability and extensive distribution,and the clinical recommended dosage of pra-ziquantel injection is 10 mg/kg.

BACKGROUND: Simple nanotube surface modification of titanium implant has been shown to promote adhesion, proliferation and differentiation of osteoblasts. Collagen coating can promote osteoblast adhesion and osseointegration in vivo. OBJECTⅠVE: To observe the effects of type collagen combined titanium dioxide nanotube composite coating modified titanium surface on osteoblast adhesion in vitro and osseointegration in vivo. METHODS: The titanium dioxide nanotube was fabricated on the pure titanium surface, then type Ⅰ collagen was combined with the nanotube structure to form composite coating. Scanning electron microscope observation was used to characterize the surface topography of the pure titanium, titanium dioxide nanotube and type Ⅰ collagen combined titanium dioxide nanotube surfaces. Contact angle test was employed to evaluate the hydrophilicity of different samples. MC3 T3-E1 murine preosteoblasts were seeded on the three kinds of materials for 4 hours. Cell adhesion morphology was examined by scanning electron microscope. Adherent cell counting was detected under inverted fluorescence microscope. Expression of actin cytoskeleton and vinculin was observed under laser scanning confocal microscope. The gene expression of vinculin and osteoprotegerin mRNA was detected by real-time quantitative PCR. The three kinds of samples were implanted into the tibia of Sprague-Dawley rats (provided by Laboratory Animal Center, Ⅰnstitute of Radiation Medicine, Chinese Academy of Medical Sciences) , and tibia samples were removed after 4 weeks of implantation for biological push-out test and histological observation. RESULTS AND CONCLUSⅠON: (1) Scanning electron microscope: There was mechanical scratch on the pure titanium surface. There was controllable, and uniform vertical arrangement of nanotubular structures with a diameter of approximately 70 nm on the titanium dioxide nanotube surface, and collagen adhered surrounding the nanotubular structures on the type Ⅰ collagen combined titanium dioxide nanotube substrate, and partial tubule orifices were closed. (2) The hydrophicility of type Ⅰ collagen combined titanium dioxide nanotube was significantly larger than those of the other two materials (P < 0.05) . (3) Compared with the pure titanium and titanium dioxide nanotube surfaces, the type Ⅰ collagen combined titanium dioxide nanotube substrate displayed increased adherent cell number, much well-organized cytoskeleton, enhanced immunofluorescence intensity of vinculin protein staining, and increased expression levels of vinculin and osteoprotegerin mRNA levels (all P < 0.05) . (4) Ⅰn vivo test revealed that the maximum push-out force in the type Ⅰ collagen combined titanium dioxide nanotube group was significantly higher than that in the pure titanium and titanium dioxide nanotube groups (P < 0.05) . Hematoxylin-eosin staining results showed that there were few bones, but many fibrous connective tissue surrounding the implant in the pure titanium group; there were more newly-born bones, and less fibrous connective tissue surrounding the implant in the titanium dioxide nanotube group; there were dense newly-born bones, and few thin fibrous connective tissue surrounding the implant in the type Ⅰ collagen combined titanium dioxide nanotube group. (5) These results indicate that type Ⅰ collagen combined titanium dioxide nanotube surface can facilitate osteoblast cell adhesion and promote osseointegration in vivo.

Objective To explore the effect of the rehabilitation self-efficacy of patient with total knee arthroplasty on the first time of ambulation after operation.Methods Totally 110 patients undergoing total knee arthroplasty were recruited,they were investigated with self-designed general information and disease situation questionnaire and recorded the first time of ambulation.The self-efficacy was measured by the Self-Efficacy for Rehabilitation outcome scale(SER).Results The earliest time of ambulation was 7.5 hours after surgery.The latest time of ambulation was 54.0 hours after surgery.The median time of the first ambulation was 46.0 h.The mean score of self-efficacy for rehabilitation therapy exercises was (28.58 ± 9.18) points,and the mean score of self-efficacy in overcoming barriers was (43.07 ± 11.04) points,and the mean score of SER was (71.65 ± 18.47) points.The total score of self-efficacy for rehabilitation therapy exercises,self-efficacy in overcoming barriers,and the score of SER were negatively correlated with the first time of ambulation (r=-0.442,-0.299,-0.399,P＜ 0.01).The self-efficacy of rehabilitation was one of the influencing factors of patient's first time of ambulation(P ＜ 0.05),which explained 9.7％ of total variance of early ambulation of patients with total knee arthroplasty.Conclusions The self-efficacy of rehabilitation after total knee arthroplasty was significantly correlated with the first time of ambulation,and the higher self-efficacy of rehabilitation,the earlier the first time of ambulation.The self-efficacy of rehabilitation was one of the important factors that affect the first time of the patient's ambulation after total knee arthroplasty.

Objective: To explore the association between hypothyroidism and sleep breathing disorders in patients with coronary heart disease (CHD). Methods: A total of 784 patients with CHD were consecutively enrolled at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. According to thyroid function test results, patients were divided into hypothyroidism group (79 cases) and non-hypothyroidism group (705 cases). All patients had undergone sleep monitoring. The sleep apnea status was compared between the two groups. Multivariate logistic regression and linear regression models were used to analyze the association between hypothyroidism and sleep breathing disorders in patients with CHD. Results: The proportion of females, mean body weight and body mass index in the hypothyroidism group were higher than those in the non-hypothyroidism group [26.6% vs.16.2%, (78.6±11.6) kg vs. (75.7±12.0) kg, (27.7±3.2) kg/m² vs. (26.6±3.5) kg/m², all P<0.05]. Patients in hypothyroidism group had a decreased average oxygen saturation (SaO₂) compared with patients in non-hypothyroidism group [ (93.2±2.9) % vs. (93.9±2.0) %, P=0.030]. In addition, events of hypoventilation in hypothyroidism group were significantly higher than those in non-hypothyroidism group[92.5 (45.8, 758.3) times vs. 68.0 (33.0, 125.0) times, P=0.013]. There were no significant differences in apnea hypopnea index, diagnosis of obstructive sleep apnea and other sleep breathing parameters between the two groups (P>0.05). A multiple linear regression analysis found that in patients with CHD, the correlation between hypothyroidism and average sleep SaO₂ was significant (β=-0.508, 95%CI -0.989--0.026, P=0.039). Conclusions: CHD patients with hypothyroidism had a lower sleep average SaO₂, and a higher sleep hypopnea events. There is a correlation between hypothyroidism and sleep hypoxia in patients with CHD. Clinical trial registration clinicalTrials.gov, NCT03362385.

Objective: To investigate the impact of moderate/severe obstructive sleep apnea (OSA) on the prognosis of acute myocardial infarction. Methods: We prospectively selected patients with acute myocardial infarction (AMI) who were hospitalized at the Emergency Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. Patients who met the inclusion criteria were examined with portable sleep respiration monitoring. Patients were divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 beats/hour) and no/mild OSA group (AHI<15 beats/hour) according to sleep AHI. The incidence of major adverse cerebrovascular events (MACCE) after discharge was compared between the two groups, and the independent risk factors of MACCE were analyzed. Results: A total of 432 patients were enrolled in this study, including 211 moderate/severe OSA patients (48.8%). Compared with no/mild OSA group,patients with moderate/severe OSA had higher body mass index ((27.17±3.22) kg/m² vs. (25.55±3.44) kg/m², t=-5.033,P<0.001), higher proportion of history of percutaneous coronary intervention (PCI) (18.5%(39/211) vs. 8.6%(19/221), χ²=9.076,P=0.003), and higher proportion of 3-vessel disease (31.3%(66/211) vs. 24.9%(55/221), χ²=10.196,P=0.017). The median follow-up time was 1.0 (0.7, 1.7) years. The incidence of MACCE in the moderate/severe OSA and no/mild group was 19.9%(42/211) and 11.3%(25/221), respectively. Kaplan-Meier analysis showed a higher cumulative risk of MACCE in patients with moderate/severe OSA (log-rank test,χ²=5.467, P=0.019). Multivariate Cox regression analysis showed that moderate/severe OSA (HR=1.915, 95%CI 1.016-3.611, P=0.045) and diabetes mellitus (HR=1.819, 95%CI 1.022-3.238, P=0.042) were independent risk factors for MACCE at 1 year post discharge in patients with AMI. Conclusions: Nearly half of AMI patients are complicated with moderate/severe OSA in this patient cohort. Coronary artery disease is more severe in AMI patients complicating with moderate/severe OSA. Moderate/severe OSA is an independent risk factor for MACCE at 1 year after discharge in patients with AMI. Whether the prognosis of AMI can be improved by intervention of OSA remains to be investigated. Trial Registration Clinical Trial.gov, NCT03362385.

Objective:To explore the characteristics and differences of oxygenated hemoglobin responses in different brain regions in adolescent depressive disorder patients and healthy adolescents during speech fluency task based on functional near-infrared spectroscopy imaging.Methods:From March 2021 to June 2021, twenty-nine adolescents with depression(depressed group) and 26 healthy adolescents(normal group) were enrolled. The severity of depression was assessed by Hamilton depression scale, and the speech fluency task was performed by functional near-infrared spectroscopy brain imaging, and the relative concentrations of oxyhemoglobin in the prefrontal and bilateral temporal lobes were measured.SPSS 26.0 statistical software was used for data analysis, chi-square test was used for gender count data. The t-test was used for comparison of two groups. The measurement data that did not conform to normal distribution were compared between the two groups by Mann-Whitney U test. Results:In the speech fluency task, there was no significant difference in the concentration of oxygenated hemoglobin in prefrontal and left temporal between the depressed group and the normal group (both P>0.05); the oxygenated hemoglobin concentration in the right temporal lobe(-9.179(-22.231, 4.789)) of depressed group was significantly lower than that of the normal group (12.754(-9.438, 35.008)), and the difference was statistically significant ( U=538.00, P<0.05). The oxygenated hemoglobin concentration in right temporal lobe of depressed group had no correlation with the score of Hamilton depression rating scale ( r=0.092, P>0.05). Conclusion:The right temporal lobe function of adolescent depression patients is lower than that of healthy controls during speech fluency tasks, which provides a basis for study of the relationship between depression and some cognitive sensitivity impairment and the function of right temporal lobe.

Objective To examine the prevalence of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS),and to evaluate the relationship of OSA with inflammatory biomarkers in ACS patients.Methods Patients with ACS treated at Beijing Anzhen Hopital from June 2015 to May 2017 were enrolled.Subjects were evaluated for OSA by sleep study,and were divided into a normal-mild OSA group (Apnea Hypopnea Index,AHI ＜ 15 times/h) and a moderate-severe OSA group (AHI ≥ 15 times/h).Laboratory examination and sleep study were monitored to analyze the effects of OSA on biomarkers by LSD-t test,Mann-whitney U test,or Chi-square test.Correlation analysis was performed to analyze the association of OSA with high sensitivity C-reactive protein (hs-CRP) by Spearman correlation anaylsis.Results A cohort of 836 patients with ACS were enrolled including 408 patients in the normal-mild OSA group and 428 patients in the moderate-severe OSA group.The levels of leukocyte(x 109L) [7.78 (6.33,9.86) vs 7.29 (6.01,9.16),P=0.006],neutrophils(× 109L) [5.05 (3.84,7.23)vs 4.80 (3.74,6.66),P=0.044],monocytes(x 109L) [0.42 (0.33,0.54) vs 0.39 (0.31,0.51),P=0.033],hsCRP(mg/L) [3.18 (1.10,11.52) vs 1.78 (0.65,6.46),P＜0.01],fibrinogen(g/L) [3.17 (2.87,3.74) vs 2.97 (2.59,3.50),P=0.002],and uric acid(μmol/L) [360 (302,422) vs 341(283,407),P=0.006] in the moderatesevere OSA group were significant higher than those in the normal-mild OSA group.AHI (correlation coefficient=0.171,R2=0.020,P＜0.01),ODI (correlation coefficient =0.201,R2=0.027,P＜0.01),and TSaO2 ＜ 90％ (correlation coefficient =0.105,R2=0.005,P＜0.01) were positively correlated with hs-CRP;minimal SaO2 (correlation coefficient=-0.100,R2=0.001,P=0.008) and mean SaO2 (correlation coefficient =-0.127,R2=0.006,P＜0.01) were negatively correlated with hs-CRP.Conclusions For patients with ACS,the level of inflammatory markers in the moderate-severe OSA group is significantly higher than that in the normal-mild OSA group.Hs-CRP is significantly associated with the severity of OSA.Diagnosis and monitoring of OSA should be considered in ACS management in the future.

Objective:The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria.Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest.Methods:Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias.Results:Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m 2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate.The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate.No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate.There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. Conclusions:Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg.These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants.

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.

Objective To explore the association of nocturnal serum cortisol levels with diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus. Methods Serum cortisol levels of 316 overweight or obese type 2 diabetic patients were tested at midnight by the method of chemiluminescence. Diabetic microvascular complications were compared among various groups according to nocturnal serum cortisol levels. All the patients with nocturnal serum cortisol level > 50 nmol/L were asked to undergo overnight low-dose dexamethasone suppression test to rule out the possibility of subclincal Cushing's syndrome. The incidences of diabetic nephropathy ( DN ) , diabetic retinopathy ( DR ) , and diabetic peripheral neuropathy ( DPN ) were examined in all the patients. Results (1)The incidence of DN was gradually increased from 13.3％to 27.7％and 44.2％in patients with low, medium, and high cortisol level groups, showing a statistical difference among 3 groups ( P<0.05) . The incidences of DR in medium and high cortisol level groups were higher than that in low cortisol level group (40.6％and 47.7％vs 22.7％, both P<0.01). The incidence of DPN in high cortisol level group was higher as compared with low cortisol level group (60.5％ vs 38.7％, P<0.01). (2) Nocturnal serum cortisol level in patients with diabetic microvascular complications was higher than that in patients without complications [ (136.87 ± 105.78 vs 97.55 ± 93.48) nmol/L, P<0.01]. Nocturnal serum cortisol level in patients with multiple diabetic microvascular complications was higher than that in patients with single diabetic microvascular complication [ (151.66±114.54vs117.69±90.26)nmol/L,P<0.05].(3)Singlefactorlogisticregressionanalysisshowedthat higher nocturnal serum cortisol level was a risk factor for diabetic microvascular complications in addition to female, age, longer diabetic duration, higher fasting plasma glucose ( FPG ) . Multivariate logistic regression analysis showed that higher nocturnal serum cortisol level was still a risk factor for diabetic microvascular complications after adjusted by diabetic duration, FPG, HbA1C, and the use of insulin (P=0.013). Conclusion Nocturnal serum cortisol level seems to be a risk factor for diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus.