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.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

The kidney governs water and is the congenital foundation.The kidney plays an important role in the transportation and distribution of body fluid,has the interior-exterior relationship with the waterffu-organ bladder,and has the meridian connection with the stomach,the reservoir of water and food,through the thoroughfare vessel.Therefore,the kidney plays a key role in the formation of phlegm.Professor CHEN Bo-Lai believes that low back pain of kidney deficiency and phlegm obstruction type is characterized by deficiency in the origin and excess in the superficiality.Excess in the superficiality is manifested as phlegm obstruction,and deficiency in the origin is manifested as kidney deficiency.Clinically,the patients with low back pain of kidney deficiency and phlegm obstruction type mainly have the manifestations of lumbosacral dull pain and fixed pain,stiffness in the waist,limb numbness or hemiplegia,accompanied by soreness and weakness of waist and knees,and preference for pressing and kneading.The treatment of low back pain of kidney deficiency and phlegm obstruction type can be based on theory of kidney being the root of phlegm,follows the therapy of tonifying kidney and eliminating phlegm,and can be performed by the modified use of basic prescription of Litan Decoction(mainly composed of Euryales Semen,Pinelliae Rhizoma,Sesami Semen Nigrum,Platycladi Semen,Paeoniae Radix Alba,Citri Reticulatae Pericarpium and Poria)together with the assistance of herbs for strengthening spleen and dispersing lung based on the differentiation of the complicated symptoms.The thoughts of Professor CHEN Bo-Lai for the differentiation and treatment of low back pain of kidney deficiency and phlegm obstruction type can be used as a reference for the treatment of low back pain with Chinese medicine.

Cancerous fever is a non-infectious fever that occurs during the progression of malignant tumors,which is directly related to the tumor or is caused by tumor treatment.Based on the yin-fire theory,Professor WANG Xi-Xing believes that the qi deficiency of spleen and stomach and the upward flaming of yin-fire are the key pathogenesis of cancerous fever.The cancerous fever involves the three zang-organs of liver,spleen and kidney,and its treatment should be achieved mainly by replenishing qi with warm-sweet medicinals,invigorating spleen and elevating yang,and clearing and purging yin-fire.Moreover,the correlation between earth(spleen)and wood(liver)should be taken into account,and harmonizing spleen and stomach can be achieved by nourishing blood and relieving depression,and soothing liver to disperse fire;the transmission of yin-fire should be blocked through the method of nourishing yin and clearing heat,and inducing fire to return to the source.After years of clinical experience,Professor WANG Xi-Xing establised Buzhong Tiaogan Decoction(mainly composed of Astragali Radix,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Cimicifugae Rhizoma,Bupleuri Radix,Angelicae Sinensis Radix,Paeoniae Radix Alba,Ophiopogonis Radix,Schisandrae Chinensis Fructus,Citri Reticulatae Pericarpium,Scolopendra,Salviae Chinensis Herba,Fructus Akebiae,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle),which is derived from Buzhong Yiqi Decoction.Buzhong Tiaogan Decoction is effective on relieving the symptoms of cancerous fever in cancer patients by benefiting the middle energizer qi,nourishing liver blood,regulating liver qi,eliminating abdominal mass and dissipating mass,so as to correct the cold,heat,yin and yang of the human body.

Objective To analyze the characteristics of adult body composition and obesity status of three ethnic groups:Ewenki,Daur and Mongolian Buryat.Methods The bioelectrical impedance analysis(BIA)was used to measure 18 body composition components in three adults ethnic groups:245(male 124,female 121)Ewenki,207(male 90,female 117)Daur,and 181(male 74,female 107)Mongolian Buryat.The data were processed using Excel 2016 and SPSS 24.0 statistical software.Results The result of correlation analysis showed that visceral fat level was significantly and positively correlated with age(P＜0.01).Stature,total body muscle mass,estimated bone mass and trunk muscle mass were all significantly and negatively correlated with age(P＜0.01)in males and females of the three ethnic groups.The percent body fat,percent left upper limb fat and percent trunk fat were positively correlated with age in Ewenki males(P＜0.05 or P＜0.01)and the percent body fat,body mass index(BMI),percent limb fat and percent trunk fat were positively correlated with age in Ewenki females(P＜0.05 or P＜0.01).Body weight,BMI,percent left upper limb fat,left upper limb muscle mass,bilateral lower limb fat and muscle mass were all negatively correlated with age in Daur males(P＜0.05 or P＜0.01).Body weight,upper limb muscle mass and left lower limb muscle mass were negatively correlated with age(P＜0.05 or P＜0.01)in Mongolian Buryat males and percent trunk fat was positively correlated with age(P＜0.05)in Mongolian Buryat females.Comparison between ethnic groups showed that most of the body composition index values of the Ewenki and Mongolian Buryat divisions were closest to each other,and the body fat content was higher than that of the Daur.BMI,percent body fat and visceral fat level were all manifested in the Mongolian Buryat Department＞Ewenki＞Daur.Cluster analysis showed that Ewenki,Daur and Mongolian Buryat were closer to the northern groups and further from the southern groups.Conclusion The Ewenki is most similar to the Mongolian Buryat in body composition characteristics all three ethnic groups has a more serious obesity problem.

Objective:This paper aims to analyze the current status,characteristics,and problems of the policy text of China's chronic disease from the perspective of full-cycle,and provide a reference for subsequent policy optimization.Methods:The author selected 104 policy documents on chronic disease published at the national level from 2009 to 2023,used content analysis method,constructed a two-dimensional analysis framework of"policy tools-full-cycle management",and carried out one-dimensional quantitative analysis and two-dimensional cross-analysis.Results:The application of policy tools is obviously unbalanced,with supply-type policy tools accounting for as much as 63.23％,and demand-type policy tools used the least,only 10.51％.In the dimension of full-cycle management,the proportions of prevention,prevention and treatment,treatment,treatment and rehabilitation,health care,and full-cycle stages are 21.01％,24.58％,28.89％,7.32％,4.69％and 13.51％respectively.It is noteworthy that the proportions of the treatment and rehabilitation,and health care stages are relatively low.All stages of chronic disease health management interact frequently with supply-type policies,and the treatment and rehabilitation,health care and full-cycle stages cross less with demand-type policy tools.Conclusion:It is necessary to adjust the proportion of policy tools,strengthen their internal coordination,improve the top-level design of treatment and rehabilitation and health care,enhance the synergistic interaction between various types of policy tools and full-cycle management,and improve the overall effectiveness of policies.

Objective:To carry out the policy diffusion analysis of centralized and volume-based drug procurement in China in recent years,and to provide reference for the formulation of centralized and volume-based drug procurement policy.Methods:Through the official websites of the central and provincial governments,the official websites of the Health Commission and the official websites of the Medical Security Bureau,the policy documents related to centralized and volume-based drug procurement from January 1,2009 to December 31,2023 were searched.Based on the policy diffusion theory,the reference network analysis method is used to analyze the intensity,breadth and speed of policy diffusion,and the sequential analysis method of policy keywords is used to analyze the direction of policy diffusion.Results:In the two stages of the development of centralized and volume-based drug procurement policy,the number of policies issued in the medical insurance management stage reached the peak;The top ten policies with the highest diffusion intensity and breadth are all central policies,and most of them are notices and opinions.In addition,the newly promulgated policies have a faster diffusion speed.In the direction of diffusion,top-down and parallel diffusion trends are obvious.Conclusion:The diffusion of centralized and volume-based drug procurement policy in China focuses on the central policy,and the diffusion speed is increasing year by year.It is suggested to strengthen the policy coordination between the central and local governments,establish a unified national information platform for centralized drug procurement,optimize the learning and competition mechanism between governments at all levels,and give play to the advantages of"policy experiment".