Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

PURPOSE: Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research. METHODS: In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model. RESULTS: Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head. CONCLUSION This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.
Animals ; Swine ; Finite Element Analysis ; Skull/injuries* ; Craniocerebral Trauma/diagnostic imaging* ; Brain ; Biomechanical Phenomena ; Scalp

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

AIM:To evaluate the underlying aetiology and clinical characteristics of retinal detachment(RD)in school-age pediatric monocular RD.METHODS:Patients with RD and contralateral blind(monocular RD)aged 7-14 years, from November 2015 to May 2021 in our hospital were retrospectively reviewed. Demographic characteristics and etiology of RD, clinical type, surgical modality, type of intraocular tamponade, pre-and postoperative visual and anatomical outcomes were recorded and evaluated.RESULTS: There were 27 children(27 eyes)with monocular RD at least 6mo follow-up. The average age at presentation was 10.63±2.30 years. Familial exudative vitreoretinopathy(FEVR)(11/27, 41%), postoperative congenital glaucoma(6/27, 22%)and Stickler syndrome(3/27, 11%)were main underlying etiologies. Among them, rhegmatogenous retinal detachment(RRD)comprised 78%(21/27)of the patients, of which 81% patients(17/21)had proliferative vitreoretinopathy(PVR)C3 or worse. Pars plana vitrectomy(PPV)was done in 85%(23/27)of the patients, of which 83%(19/23)received silicone oil tamponade. Best corrected visual acuity(BCVA, LogMAR)worse than 1.7 was seen in 78%(21/27)of the patients at final visit, and 82%(22/27)had reattached retina, but 41%(11/27)of the patients remained status of silicone oil tamponade at last visit.CONCLUSION:School-age pediatric monocular RD is often associated with underlying congenital or hereditary conditions, and often presented with severe RD and severe PVR reaction which needed vitrectomy combined with silicon oil tamponade, and with poor visual and anatomical short-term prognosis.

APACHE ; Humans ; Microtubule-Associated Proteins ; Multiple Organ Failure ; Sepsis ; Shock, Septic

We aimed to explore the associations between the age at which children undergo surgery for hypospadias and a range of social and clinical factors in a single center. Our aim was to promote the early surgical treatment of children with hypospadias. For a 6-year period, social and clinical data were collected from all children undergoing surgery to repair hypospadias in Children's Hospital of Chongqing Medical University (Chongqing, China), located in southwest of China. We analyzed the correlations between age at surgery and a range of social and clinical factors. A total of 1611 eligible cases were recruited, with a mean age of 54.3 months and a median age of 42 months: 234 cases (14.5%) were classified into a "timely operation" group, 419 (26.0%) cases into a "subtimely operation" group, and 958 (59.5%) cases into a "delayed operation" group. According to multivariate regression analyses, the higher the regional economic level, the closer the urethral opening to the perineum, and the higher the educational level of the guardians was, the younger the children were when they underwent the initial surgery for hypospadias; this was also the case for families without other children. Our subgroup analysis showed that the primary educational level of the guardians was a risk factor for subtimely surgery in their children (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.08-2.15, P < 0.05). A lower regional economic level (OR = 1.87, 95% CI: 1.26-2.78, P < 0.01), a lower educational level of the guardians (OR = 3.84, 95% CI: 2.31-6.41, P < 0.01), and an anterior-segment urethral opening (OR

Objective:To summarize critical cases of emergency helicopter transferring between hospitals and improve the quality and safety of critical care.Methods:The task records of Guangxi Aviation Medical Rescue Training Base from September 2017 to September 2020 were retrieved. The mission acceptance, implementation results, disease spectrum composition, pre-transfer preparation and medical intervention on board were summarized.Results:① General information: a total of 168 patients of helicopter transfer requests were registered, of which 36 patients were transferred, 35 patients were successful, 1 patient had cardiac arrest during the landing phase, and died several hours after continuous resuscitation. Of the 36 patients 30 were males and 6 were females, with median age of 50.5 (29.8, 66.0) years old, the average transfer time was (54.95±17.89) minutes, and the average transfer distance was (205.74±74.68) km. ② Disease spectrum included 11 cases of stroke (30.55%), 7 cases of trauma (19.45%), 5 cases of severe pneumonia (13.89%), 5 cases of heart and macro-vascular diseases (13.89%), 5 cases of abdominal emergency (13.89%), and 3 other conditions (8.33%).③ Severity: 31 patients (86.11%) were severe (≥15) according to acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score; 19 patients (52.78%) were high-risk emergency transport (≥6) according to Hamilton early warning score (HEWS); 6 patients (85.71% of trauma patients) were severe trauma (≥16) according to injury severity score (ISS). ④ Preparation before transfer: remote consultation was carried out to evaluate the latest state of the patient's condition, especially the respiratory and circulatory conditions. Relevant items were reviewed and emergency treatments were implemented when necessary. Targeted preparation was made for accidents that might occur during transfer, such as electrocardiogram (94.44%), blood gas analysis (94.44%), brain CT (36.11%) and other auxiliary examinations, endotracheal intubation or tracheotomy (72.22%), deep vein catheterization (91.67%), placement of gastric tube (86.11%) and urinary tube (88.89%), adjustment of sedative (38.89%), vasoactive drugs (58.33%) and drugs for dehydration and lowering intracranial pressure (33.33%), and fixation of fracture (11.11%), etc. ⑤ On-board medical intervention: cardiac monitoring, blood pressure, respiration and blood oxygen monitoring were carried out in all patients. The parameters of patients using ventilator were adjusted in time (66.67%). The dosage of patients using micropump was adjusted in time (91.67%). Other aspects included the use of sedative and analgesics (38.89%), sputum suction nursing (75.00%), all kinds of catheter nursing (endotracheal intubation/incision nursing of 72.22%, indwelling catheter nursing of 88.89%), and cardiopulmonary resuscitation for patient with cardiac arrest (2.78%).Conclusion:As the patients transferred by helicopter are mainly those of critically ill at this stage, the requirements for airborne medical equipment and rescue technology are high, and there is an urgent need to establish technical specifications and personnel training standards.

Objective:To analyze the changes of soil microbial community structure before and after planting Gastrodia elata in different producing areas，and to investigate the response of soil microorganisms to the planting of G. elata. Method:ITS and 16S rDNA high-throughput sequencing technologies were used to detect fungal and bacterial community compositions in the soil，including the soil without planting G. elata（CK1，CK2），the soil around G. elata（GE1，GE2）before harvesting, and the soil around the rhizomorph of Armillaria（AGE1，AGE2） in Dafang, Guizhou and Jinzhai, Anhui respectively. Result:Principal component analysis (PCA) showed that the soil microorganisms changed significantly after G. elata planting as compared with the control soil. The sequencing results showed that the planting of G. elata increased the OTUs number of fungi and bacteria. As compared with the control soil，the diversity and abundance of fungal and bacterial communities showed an increase trend after the cultivation of G. elata in soil of Dafang, Guizhou， such changes of fungal communities were not significant, but the abundance of soil bacteria communities increased in Jinzhai, Anhui as compared with the control soil. The abundance of genera Ilyonectria and Nitrospira increased，while genera Russula decreased significantly both in the soil of Guizhou and Anhui. Furthermore，the abundance of Fusarium and Mortierella increased significantly in the soil of Dafang, Guizhou. Conclusion:The soil microorganisms were out of balance after planting of G. elata, and the abundance of pathogenic microorganisms such as Ilyonectria and Fusarium increased，which may be related to the plant diseases and insect pests of G. elata.