Nasal spray can treat local diseases such as rhinitis, it also plays an important role in the treatment of systemic diseases including vaccine immunity. As a drug-device combination product, spray pattern is often used as the quality indicator of nasal spray to ensure its quality, plume geometry can not only be combined with the spray pattern to evaluate the performance of the nasal spray, but also can predict the deposition of the nasal spray in the nasal cavity. This article systematically reviews the definition and measurement methods of the spray pattern and plume geometry of nasal spray and their correlation with nasal deposition behavior. The measurement parameters of spray pattern and plume geometry are defined. The influence of formulation, device and trigger parameters on spray pattern and plume geometry is clarified. The correlation between various parameters and nasal deposition is analyzed. The measurement parameters are classified according to the size and shape of the spray. Plume angle is closely related to the deposition of drugs in the nasal cavity. Jet-like plume with a smaller plume angle can increase the navigation ability of the nasal spray in the curved anatomical structure of the nasal cavity, which is conducive to increase drug deposition. This makes it possible to increase deposition of the nasal spray in the nasal cavity via appropriately increasing viscosity and thixotropy of the nasal spray formulation. This review provides the theoretical basis for the high quality nasal spray product development.

This paper was designed in middle cerebral artery occlusion (MCAO) model of rats, to explore the role of transient receptor potential channel 4 (TRPC4) as Ca(2+) selective channel by detecting the changes of the expression of TRPC4 in different parts of cerebral tissues under the condition of focal cerebral ischemia. The rats were sacrificed after MCAO surviving time 6 h, 12 h, 1 d, 3 d. As determined by Western blot, the expressions of TRPC4 in striatum and hippocampus of 12 h, 1 d, 3 d groups were significant higher than that in the control group (P<0.05). Immunohistochemical staining showed that the TRPC4 immunoreactive substances were present in the membrane of neurons. Compared with the control group, immunostaining positive cells increased in hippocampus and striatum of cerebral ischemia groups. The TRPC4 immunostaining positive cells increased significantly in 1d-group and 3d-group (P<0.05). It suggests that as a Ca(2+) selective channel, the variance of the expression of TRPC4 may play a role in acute and delayed neuronal injury in focal cerebral ischemia.
Animals ; Cation Transport Proteins ; biosynthesis ; genetics ; Corpus Striatum ; metabolism ; Hippocampus ; metabolism ; Infarction, Middle Cerebral Artery ; metabolism ; Ion Channels ; biosynthesis ; genetics ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; TRPV Cation Channels

1 approximately 3 days old Piglet's primary preadipocytes in vitro were cultured and treated with 0micromol/L (control group), 10microlmol/L (lower dose group), 20micromol/L(middle dose group) and 50micromol/L, 100micromol/L (higher dose group) RES. Cell proliferation and viability were analyzed by MTT assay. The degree of differentiation and adipogenesis were measured by Oil Red O staining extraction assay and the expression of Sirt1 (sirtuin) mRNA were detected by RT-PCR. The results showed the optical density (OD) of MTT and Oil Red O staining were all decreased, especially treated by 50micromol/L, 100micromol/L RES at 72h and 96h (P < 0.01); the ratio of OD of the expression of Sirt1 mRNA to that of beta-actin mRNA were increased after treated by 100micromol/L RES (P < 0.01). RES can inhibit proliferation and differentiation of pig preadipocytes in certain degree. Higher dose of RES can markedly decrease adipogenesis and prevent preadipocytes differentiation into adipocytes, which may be in part associated with its effect on increasing the expression of Sirt1 mRNA.
Adipocytes ; cytology ; drug effects ; metabolism ; Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; RNA, Messenger ; analysis ; Sirtuin 1 ; genetics ; Stem Cells ; drug effects ; Stilbenes ; pharmacology ; Swine ; Transcription, Genetic

Immunohistochemistry and double immunofluorescent labeling techniques combined with confocal laser scanning microscope analysis were used to investigate the characteristic spatial induction profile of nestin following a transient middle cerebral artery occlusion in adult rat brain. The results showed that nestin was induced in ischemic core at 1 day after reperfusion. In addition to ischemic core, the expression of nestin increased in peri-ischemic I, II and III regions at 3 days and 1 week, then it decreased and narrowed along the rim of ischemic core 2 weeks after reperfusion. Double immunofluorescent labeling showed that nestin positive cells were mostly co-stained with GFAP,a astrocyte marker, in peri-ischemic I region 3 days after reperfusion. At 2 weeks, however nestin cells showed a long process and the cells double stained with nestin and NSE,a neuonal specific marker,increased in the ischemic brain. The results suggest that cerebral ischemia induces nestin expression in damaged neurons which might favor the neuroprotection against ischemic damage.
Animals ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; pathology ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; Nestin ; metabolism ; Neurons ; metabolism ; Rats

Three-dimensional (3D) culture of cells could closely mimic the in vivo situation with regard to cell function and microenvironment compared with plane monolayer cultured cells. In this paper, we established 3D culture of rat WB-F344 cells with rotary cell culture system (RCCS) to simulate microgravity environment, and examined cells proliferation, morphology, microstructure, E-cadherin protein quantity and mRNA expression of adhesion molecules by count the number of cells, optical microscope, transmission electron microscope and reverse transcriptase-polymerase chain reaction (RT-PCR). The results demonstrated that cells were polyhedron with lots of micovilli and mitochondria, which grow well and packed together densely to form irregular aggregates. Adjacent cells were connected with desmosome and tight junction. With the regard, the aggregates behaved 3D growth characteristics. Moreover, compared with control, mRNA level of Fibronectin and E-cadherin protein were increased, the changes maybe is the part mechanism in this microgravity simulated cells culture models which strengthened cells junction. This rotating 3D model might facilitate the study of interactions of cell-cell, cell-matrix and the mechanisms.
Animals ; Cadherins ; genetics ; Cell Adhesion ; Cell Culture Techniques ; methods ; Cell Proliferation ; Fibronectins ; genetics ; Rats ; Spheroids, Cellular ; ultrastructure ; Weightlessness Simulation

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular/genetics* ; 22q11 Deletion Syndrome ; Fetus

Objective To evaluate the effects of small interfering RNA(siRNA)against Ki67 gene on the proliferation and apoptosis of human renal carcinoma cell line 786-0 cells.Methods The human renal carcinoma 786-0 cells were treated with Ki67-siRNA(100 nmol/L).The mRNA expression of Ki67 was detected by RT-PCR.The protein expression of Ki67 was detected by Western blot and immunohisto- chemical technique,respectively.The proliferation of 786-0 cells was detected by MTT assay.The apoptosis of 786-0 cells was detected by TUNEL assay.Results RT-PCR and Western blot analysis showed that the Ki67 mRNA and Ki67 protein expression levels of the 786-0 cells treated with Ki67-siRNA were(37.6?1.9)% and(46.4?0.9)% ,respectively,which were significantly lower than those of controls [(97.3?0.9)% and(95.3?0.9)%,P＜0.01],The Ki67 positive expression rate of 786-0 cells treated with Ki67-siRNA by immunohistochemical technique was 52.5?2.3,which was significantly lower than that of controls(114.5?4.9 ,P＜0.01).The proliferation-inhibiting rate and apoptosis rate of the 786-0 cells trea- ted with Ki67-siRNA were( 63.6?1.6)% and(41.7?0.6)% ,respectively,which were significantly higher than those of controls [(2.8?0.2)% and(10.3?1.4)%,P＜0.01].Conclusions siRNA against Ki67 gene can inhibit the proliferation and induce the apoptosis by blocking Ki67 expression of hu- man renal carcinoma 786-0 cells.The inhibition of Ki67 expression by siRNA may be a promising approach in gene therapy for renal cancer.

OBJECTIVE: To assess the diagnostic value of copy number variation sequencing (CNV-seq) in the genetic etiology of fetuses with nasal bone dysplasia (NBD). METHODS: A total of 217 fetuses discovered with NBD from December 2017 to December 2020 were divided into the isolated NBD group and NBD combined with other anomalies group, for which copy number variations (CNVs) were analyzed. RESULTS: A total of 40 fetal abnormalities were detected in 217 cases, with an overall abnormal rate of 18.4%. These included 31 cases with aneuploidies (14.3%, 31/217) and 9 cases with genomic CNVs (4.1%, 9/217). Five cases of trisomy 21 (3.5%, 5/144) and two CNVs cases with unknown clinical significance (1.4%, 2/144) were detected in the isolated group. As for the combined NBD group, 26 aneuploidies (35.6%, 26/73), including 19 cases with trisomy 21, 6 cases with trisomy 18, 1 case with trisomy 13, 5 cases with pathogenic CNVs (6.8%, 5/73), and 2 cases with CNVs of unknown clinical significance (2.7%, 2/73) were detected. A significant difference was detected between the two groups (P < 0.01). CONCLUSION The detection rate of CNV-seq is high for chromosomal aneuploidies and pathogenic CNVs in fetuses with NBD, particularly in those combined with other ultrasonic abnormalities.
Aneuploidy ; Bone Diseases, Developmental ; Chromosome Aberrations ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy

Objective: To investigate the incidence and clinical features to probe the risk factors of hemorrhagic cystitis (HC) in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Medical records of 62 children and 27 adolescents with hematological diseases treated with haplo-HSCT between 2015 and 2016 were analyzed. Results: Of 89 cases (56 boys and 33 girls) , 44 patients were diagnosed with ALL, 33 AML, 3 AHL and 9 MDS. HC occurred in 32 of the 89 patients with an incidence of 36%, including 6 with grade Ⅰ, 16 with grade Ⅱ, 8 with grade Ⅲ, 2 with grade Ⅳ HC, respectively. The median time of HC onset was 25 days (range 2-55 days) after haplo-HSCT with the median duration as 19 days (range 3-95 days) , all of them were cured. The incidence of HC was lower in the group of children than that in the group of adolescents (27.4% vs 55.6%, χ(2)=6.466, P<0.05) , and the incidence of HC was higher in the group of patients who were ≥5 years old than that in the group of patients who were <5 years old (0 vs 34%, χ(2)=4.043, P<0.05) . Conclusion: HC is one of common complications in children and adolescents with hematological diseases post haplo-HSCT, older age was associated with increased mortality.
Adolescent ; Child ; Child, Preschool ; Cystitis ; Female ; Hematologic Diseases ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Male ; Retrospective Studies ; Risk Factors

Objective To determine the key factors affecting the quality of Kaixin San Heart-opening powder and the best preparation forms of Kaixin San,laying the groundwork of anti-dementia drug devel-opment from Kaixin San.Methods The content of effective index components of medicinal-preparation of Kaixin San was detected by using HPLC.The quality of medicinal preparation from Kaixin San were characterized based on the content,relative quantity,relative ratio of content,yield rate and anti-dementia effect,and the characterized results were given correlation analysis.Results The method of the determi-nation of effective index components from Kaixin San is easy to handle,accurate and highly reproducible. The effect of anti-dementia of three medicinal preparations from Kaixin San was listed in the following de-scending order of enrichment,ethanol extract,and water extract.The content of effective index compo-nents is higher with unique proportion,lower extraction rate,lower dosage and higher antibacterial effect, which is the best form in medicinal-preparation application of Kaixin San.Conclusion The key to the improvment of efficacy is to explore the fittest content and relative ratio of medicinal components based on the basic composition of Kaixin San and yield rate.