Objective To study the characteristics of pharmacokinetics and pharmacodynamics of insulin dry powder inhalation and its relative bioavailability as compared with subcutaneous injection of regular insulin. Methods In this open,single-center,randomized,two-period,cross-over,euglycemic glucose clamp study,18 healthy volunteers(14 men and 4 women),aged(24.9?1.7)years,with body mass index(20.6?1.2)kg/m~2, received the insulin dry powder inhalatin(80 U)or regular insulin(15 U)subcutaneous administration.The blood samples of this study at 0,20,30,40,50,60,70,80,90,100,110,120,135,150,165,180,195, 210,225,240,270,300,330,360,390,420,450 and 480 rain were taken for serum insulin measurement, meanwhile,glucose infusion rates(GIR)were determined per 5 minutes over a period of 8 hours.Results The C_(max)were(57.9?17.8 vs 114.5?29.7)mU/L(tested vs reference preparation),T_(max)were(46.7?45.6 vs 107.8?33.7)min,GIR_(max)were(3.35?0.98 vs 5.17?1.75)mg?kg~(-1)?min~(-1)and T_(GIRmax)were(88.3?17.0 vs 151.9?34.6)min.The relative bioavailability was(10.26?2.25)%,and the relative bioefficacy was(14.33?7.26)%.Conclusion The study shows that insulin dry powder inhalation is absorbed via lungs and its action sets in earlier than that of the regular insulin injected subcutaneously.These pharmacokinetie and pharmacodynamic data may provide a reliabe guide for further clinical trial.

Objective To study the rationality and possibility of 64 slice spiral CT in the examination of the temporal bone at low dose.Methods The same CT technique and temporal bone mode as those for clinical CT were used,two cranium specimens(four ears)were scanned with Somatom Sensation 64-slice spiral CT at different mA(380,300,200,160,120,80),and muhi-planar reformation was performed.The CT dose index at different mA groups were measured by 10 cm pencil ionization chamber and head dose phantom.Four anatomic structures on axial images(subarcuate fossa,tendon of tensor tympani, facial recess,etc),four anatomic structures on coronal images(scute,crista transversa,fenestra cochleae, etc)and six anatomic structures on double oblique images(malleus,incus,stirrup bone,upper bony semicircular,etc)were chosen to evaluate and grade the reformation images among different mA groups,and to determine the minimum mA value.Ten ears of five patients were used to test the validity of the minimum mA value.Results CT radiation dose was significantly reduced from(47.8?2.7)to(20.1?2.0)raCy (P

Objective To investigate the impact of cyclosporine A (CsA) on atrial expression change of L-type calcium channel αlc subunit in a canine model of atrial fibrillation (AF). Methods AF was induced by rapid atrial pacing (400 baets/min) for 8 weeks in adult male dogs and placebo (n=6) or CsA (5 mg·kg-1·d-1, n=6) were orally administered to these animals. Sham operated animals served as normal controls (n=6). The atrial electrophysiological parameters including P wave duration, atrial effective refractory period (AERP) were recorded and analyzed at baseline and 8 weeks later. Animals were scarified at 8 weeks post final electrophysiological examinations and atrial expressions of L-type calcium channel αlc subunit were determined by Western blot. Results Compared to sham group, the P wave duration was significantly prolonged while AERP was significantly decreased in AF and CsA groups (all P <0. 05). AERP was significantly longer in CsA group than that in AF group (P < 0. 05 ). L-type calcium channel αlc subunit expression was significantly downregulated in AF group compared to sham group (P <0. 05) and CsA significantly attenuated this downregulation (P < 0. 01 vs. AF group). Conclusion CsA could attenuate the downreguahion of the L-type calcium channel αlc subunit expression and improve the atrial electrophysiological remodeling in this canine model of AF.

Objective To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2,and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma.Methods The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2.CNE-2R and CNE-2 cells were cultured and administered with 60Co γ-ray irradiation at the dose of 400 cGy for 15 times.Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes.Bioinformatic analysis was used to identify the pathways related to radioresistance.Results The number of the differentially expressed genes that were found in these 2 experiments was 374.The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN,MYD88,CCL5,CXCL10,STAT1,LY96,FOS,CCL3,IL-6,IL-8,IL-1α,IL-1B,and IRAK2(t=13.47-66.57,P<0.05).Conclusions Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance.

Objective To investigate the effects of ciyelosporine-A(CsA).a calcinenrin(CAN)inhibitor,on electrophysiological propertiesof atria in canine tachycardia-induced model of AF.Methods Eighteen healthy adult mongrel canines weighing 17.0 to 23.2 kg(rangedfrom 2 to 4 years old)were randomized to 3 groups,Sham group(no pacemaker was implanted),atrial tachypacing group(ATP group)each group at baseline and after 8 weeks' tachypacing.Measurements included atrial effective refractory period(AERP),conductionvelocity(CV),wave length(WE),atrial fibrillation load and rate-adaptability. Results After 8 weeks' atrial tachypacing,ATP andCsA groups showed significant longer duration of the P wave,shorter AERP,decreased adaptation of AERE slower CV,shorter Wland longer AF duration compared to the shamg roup (all P＜0.05).AERP of the CsA group was longer than that of ATP group (P＜0.05),but there were no differences in rate-adaptability,CV,incidence of induced AF and AF duration between CsA group and ATP group.Conclusions Our results suggest that calcineurin pathway intervention by CsA have a positive effect on tachycardia-inducedelectrical remodeling of atria,but can not prevent or reverse AF.

Usung gatufloxacun ( GTFX) as template molecule, magnetuc surface molecularly umprunted polymers ( M-MIPs) were prepared on the surface of modufued magnetuc suluca ( Fe3 O4@SuO2 ) wuth surface molecular umpruntung technuque. The polymers were characteruzed by transmussuon electron mucroscopy ( TEM ) and vubratung sample magnetometer ( VSM ) . The statuc adsorptuon experuments and Scatchard analysus suggested that there were two types of bundung sutes un the M-MIPs. The maxumum adsorptuon capacutues of M-MIPs and magnetuc non-umprunted polymers ( M-NIPs) for GTFX were 35. 1 mg/g and 23. 1 mg/g, respectuvely. The selectuvuty coeffucuents of GTFX M-MIPs to cuprofloxacun (CPFX), norfloxacun (NFLX), melamune (MEL) and tetracyclune (TC) were 2. 43, 5. 18, 6. 61 and 12. 99, and the relatuve selectuvuty coeffucuents of M-MIPs to M-NIPs for these four drugs were 2. 09, 1. 95, 3. 15 and 2. 43, respectuvely, unducatung the good specufuc recognutuon capabuluty for GTFX. Combuned wuth hugh performance luquud chromatographuc analysus, the M-MIPs were applued to extract and enruch GTFX un mulk sample wuth the recoverues more than 91 . 5%.

OBJECTIVETo study the expression of the receptor for advanced glycation end products (RAGE) and the inhibitory effect of advanced glycation end products (AGEs) on testosterone production in rat Leydig cells.

METHODSRat Leydig cells were primarily cultured and the expression of RAGE in the Leydig cells was detected by RT-PCR and immunofluorescence staining. The Leydig cells were treated with AGEs at the concentrations of 25, 50, 100 and 200 microg/ml, respectively, and the testosterone content was determined by ELISA.

RESULTSRT-PCR and immunofluorescence staining exhibited the expression of RAGE in the rat Leydig cells. AGEs remarkably suppressed hCG-induced testosterone production in the Leydig cells in a concentration-dependent manner in the 50, 100 and 200 microg/ml groups as compared with the control (P < 0.01).

CONCLUSIONRAGE exists in rat Leydig cells and AGEs can significantly inhibit the secretion of testosterone in primarily cultured rat Leydig cells.

Animals ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Glycation End Products, Advanced ; pharmacology ; Leydig Cells ; metabolism ; radiation effects ; Male ; Rats ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Testosterone ; biosynthesis

Objective To summarize and analyze the epidemiological and clinical characteristics of COVID-19 Omicron variant cases in makeshift hospital, and the influence of age, sex and vaccination status on the disease duration, so as to provide reference for the prevention and control of the COVID-19 epidemic. Methods The epidemiological and clinical characteristics of COVID-19 cases admitted to makeshift hospital of National Convention and Exhibition Center (Shanghai) from April 9 to May 31, 2022 were retrospectively described and analyzed, and further cohort analysis was conducted to determine the influence of age, sex and vaccination status on the disease duration of COVID-19 cases in the author's branch hospital. Results Among the 174 466 COVID-19 cases in makeshift hospital, most of them were male, accounting for 59.38%. The infected cases were mainly young and middle-aged people aged 18-59 years old, accounting for 83.50%, followed by 12.30% of the elderly group over 60 years old; the average hospital stay was 7.40 days; the proportion of patients with fever was less than 27.79%; 15.37% (26 817/174 466) of the patients complicated with underlying diseases, and the top three were hypertension, diabetes and coronary heart disease. The proportion of people who received COVID-19 vaccine accounted for 79.56% (13 799/17 956), of which the highest proportion of three doses was 44.09%. The disease duration of 17 956 COVID-19 cases in the author's branch of makeshift hospital was 10.18 (7.34, 13.05) days. The disease duration in the elderly group was the longest with 11.34 (8.35, 14.37) days, followed by 11.17 (9.07, 14.33) days in the preschool group, 10.37 (8.14, 13.34)· days in the middle-aged group, 10.07 (7.37, 12.37) days in the school-age group, and 9.34 (7.05, 12.16) days in the young group. There was significant difference in the overall distribution of disease duration among the five groups (H=550.479 P<0.01). The disease duration in each age group basically showed a V-shaped distribution. The disease duration was 10.27 (7.34, 12.57) days in males and 10.10 (7.25, 13.09) days in females, and there was no significant difference (Z=-1.505 P>0.05). The disease duration of vaccinated patients was 10.24 (7.35, 13.05) days, and that of unvaccinated patients was 9.47 (7.09, 12.47) days. There was significant difference between the two groups (Z=-4.338 P<0.01). Conclusions COVID-19 Omicron variant cases have a high proportion of males, mainly young and middle-aged, and the proportion of fever patients is less than 30%. The disease duration is significantly lower than that of the original strain in Wuhan, and shows "V" distribution with each age group. Sex had no effect on the disease duration. COVID-19 vaccination did not have a clinical effect on the disease duration.

Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.