Nimodipine is the second generation of dihydropyridine Ca2+ antagonist. The scope of its clinical application has been expanded because of the excellent curative effects on cerebrovascular diseases. Nimodipine is commonly available on the market as oral or injection preparation,which has to be given several times per day. It may induce peripheral cholinergia side effects and has low bioavailability. Therefore,it is necessary to develop novel drug formulation with optimized delivery system. In the present review, an attempt is made to discuss the current progress of nimodipine in pharmaceutics,including the difference of market situation,safety and efficacy of different dosage forms. Meanwhile,the main research directions of new dosage forms are summarized,which can pro-vide reference for developing more efficient and convenient nimodipine preparations.

OBJECTIVE:To establish a method for simultaneous determination of lysophosphatidyl choline(LPC)and lysophos-phatidyl ethanolamine(LPE)in Nimodipine fat emulsion. METHODS:HPLC was performed on the column of Lichrosher Diol with detector of evaporative light scattering detector with mobile phase A of heptane- isopropyl alcohol solution(43∶57,V/V),mobile phase B n-heptane-isopropyl alcohol-water(29.5∶59∶11.5,V/V/V)(gradient elution)at a flow rate of 1.5 ml/min,column tempera-ture was 40℃,and the injection volume was 20 μl. RESULTS:The linear range was 0.020 0-0.400 0 mg/ml for LPC(r=0.999 0)and 0.010 0-0.200 0 mg/ml for LPE(r=0.999 6),and the logarithm value of concentration and peak area showed good linear relationship;the limit of quantitation was 0.013 4 mg/ml for LPC and 0.013 0 mg/ml for LPE;the limit of detection was 0.007 8 mg/ml for LPC and 0.007 6 mg/ml for LPE;RSDs of precision,stability and reproducibility tests were lower than 2%;recoveries were 95.96%-100.63%(RSD=1.83%,n=9)and 99.22%-101.76%(RSD=0.80%,n=9). CONCLUSIONS:The method is simple,and can be used for the determination of related substance in Nimodipine fat emulsion.

To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21)%, (11.71 ± 0.39)%, (15.41 ± 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64)% and (5.66 ± 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres.

Objective To establish a high performance liquid chromatography method to detect the concentration of lamotrigine in blood dialysate and investigate in vitro recovery of lamotrigine and the factors.Select the microdialysis conditions that apply to the animal experiment and guide the stability study of in vivo recovery.Methods Positive dialysis and retrodialysis were used for the examination of lamotrigine in vitro recovery and the influencing factors such as flow rate, concentration, temperature and time.Filtered out the best conditions that apply to the in vivo experiment.Used the retrodialysis to determine the in vivo recovery and its stability.Results There was no significant difference between relative recovery and relative loss in the same flow rate.The concentration had no obvious effect on relative recovery.At the same condition,relative recovery decreased with the increase of the flow rate and increased with the temperature.The in vivo recovery had a good stability of 6.5 hours when the flow rate and stabilization time were set at 2μL/min and 1.5 h, respectivily.Conclusion Microdialysis technique can be used for the pharmacokinetic study of lamotrigine.Retrodialysis can be used for the determination of the lamotrigine in vivo recovery.

AIM: To detect the expression of cytoplasmic inhibitor of apoptosis protein 2 (c-IAP2) and growth arrest-specific gene 1 (GAS1) in Hodgkin's lymphoma (HL) and anaplastic large cell lymphoma (ALCL) and to investigate the role of two genes in the pathogenesis of HL and ALCL.METHODS: HE staining,the antibodies CD30,CD15,CD45RO and CD20 were used to screen the cases of HL and ALCL from 288 cases of lymphoma. The clarified HL and ALCL were subjected for immunohistochemical staining by SP and ABC methods to analyze the expression of c-IAP2 and GAS1. RESULTS: ①The positive rate of c-IAP2 in HL was 25/26(96.1%) while that in ALCL was 6/19(31.6%),there presented statistic significance between HL and ALCL groups( P

AIM: This study is based on the result of the study in HL and ALCL employing gene chip technique, in which writer found that there was distinctly different expression of caspase-4 between HL and ALCL cell lines at the level of mRNA. From the point of view, we try to identify at the level of protein whether there is different expression of this gene in HL and ALCL tissues as well. METHODS: HE staining, the monoclonal antibodies CD30 (BerH2), CD15 (C3D-1), CD20 (L26) and CD45RO (UCHL1) were used for selecting the cases of HL and ALCL. Specific high affinitive anti-caspase-4 polyclonal antibody was used by immunohistochemical staining to analyze the expression of caspase-4 in 18 cases of HL and 15 cases of ALCL. RESULTS: The expression of caspase-4 demonstrated a strong positive staining in all ALCL cases (15/15,100%), whereas negative in 16 HL cases (88 8%), while other two cases were weakly stained (11 2%), showing a distinct difference (P

Objective:To determine the anatomical parameters concerning the length, width and height of the sustentaculum fragment of the calcaneus using CT imaging data and their clinical significance.Methods:A retrospective study was conducted to analyze the CT imaging data of normal calcaneus in 96 patients (100 feet) which had been collected by Department of Orthopedics, Shanghai Tongji Hospital from January 2019 to September 2020. There were 45 males (48 feet) and 51 females (52 feet) with an age of (42.1±13.6) years, and 56 left feet and 44 right feet. After 3D models were reconstructed with the CT data using software Mimics 22.0, the calcaneus was viewed layer by layer at each level of the scan. After the first continuous bone trabecula on the medial side of the calcaneal central triangle was taken as the boundary, the model of the sustentaculum fragment was segmented. The length, width, and height of the sustentaculum fragment were measured. The outer contour of the sustentaculum fragment was projected onto the lateral wall of the calcaneus to draw the contour line using software Materialise 3-Matic 22.0. By overlaying projection line diagrams, a summary of projection line diagrams of 100 sustentaculum fragments was obtained. Seven screw insertion points were selected in the summary region of the projection line diagrams of the lateral wall of the calcaneus, and the distance from each point to the medial side of the calcaneus were measureed. The length, width, and height of the sustentaculum fragment, as well as the distance from the 7 insertion points to the medial side of the calcaneus, were compared between different feet and genders.Results:The length, width, and height of the sustentaculum fragment were (45.19±4.60) mm, (38.57±4.59) mm and (40.76±5.48) mm, respectively. There were no significant differences in the length, width or height of the sustentaculum fragment between different feet or in the height of the sustentaculum fragment between different genders ( P>0.05), but the length and width of the sustentaculum fragment in females were significantly smaller than those in the males ( P<0.05). The projection of the sustentaculum fragment was approximately ellipse on the summary region of the projection line diagrams on the lateral wall of the calcaneus, with the long axis approximately parallel to the midpoint tangent of the lateral edge of the calcaneal posterior articular surface, ranging from 2 to 20 mm from the posterior articular surface. The distances from the 7 insertion points to the medial surface of the calcaneus were (39.91±3.77) mm at point A, (40.89±3.55) mm at point B, (36.42±5.98) mm at point C, (39.12±5.52) mm at point D, (40.04±4.84) mm at point E, (33.00±3.96) mm at point F, and (33.04±3.82) mm at point H. There was no significant difference in the distances from the 7 insertion points to the medial surface of the calcaneus between different feet ( P>0.05), but the distances from the 7 insertion points to the medial surface of the calcaneus in the females were significantly smaller than those in the males ( P<0.05). Conclusions:Anatomical measurements of the sustentaculum fragment can provide a theoretical basis for the range of fixation of the sustentaculum screws. A summary of projection line diagrams of the sustentaculum fragment on the lateral surface of the calcaneus can serve as a reference for placement of sustentaculum screws. Measurement of the distances from 7 insertion points to the medial surface of the calcaneus can facilitate determination of the lengths of sustentaculum screws.

Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.

ObjectiveTo explore the possible mechanism of Bimin Formula （鼻敏方） in treating lung-spleen qi deficiency syndrome of allergic rhinitis （AR） with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose Bimin Formula group （8 rats）， and a high-dose Bimin Formula group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （P＜0.05 or P＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （P＜0.05 or P＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （P＜0.05 or P＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （P＞0.05）. Compared with the low-dose Bimin Formula group， the expression of NF-κB protein in the high-dose group decreased （P＜0.01）. ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.

OBJECTIVEPrevious studies have demonstrated that two homozygous missense MYO1E mutations are associated with childhood autosomal recessive focal segmental glomerulosclerosis in steroid-resistant nephrotic syndrome (SRNS) families from Italy and Turkey. Non-disease-causing heterozygous MYO1E variants were also found in other SRNS patient cohorts. However, the role of MYO1E mutations in Chinese sporadic SRNS has not been established.

METHODPeripheral blood samples were collected for genetic analysis from 54 children with sporadic SRNS in Chinese Han ethnic group and a normal control group of 59 healthy adult volunteers. None of the patients carried mutations in NPHS2 or WT1. Genomic DNA was extracted from peripheral blood leukocytes. Twenty-eight exons and exon-intron boundaries of the MYO1E gene were amplified by polymerase chain reaction. Mutational analysis was performed by direct DNA sequencing and restriction endonuclease digestion.

RESULTFifty-one variants in the MYO1E gene were identified in 54 children with sporadic SRNS. Among them, 10 MYO1E mutations of IVS1-11T>C, IVS2-86T>A, 279T>C (D93D), IVS6-181G>A, 718C>T (L240F), 1678A>G (T560A), IVS16-35A>G, IVS18+48T>A, IVS19+38G>A and IVS25+13C>T were detected in 11 patients, whereas they were absent in the 59 normal Chinese controls. Forty-one variants in MYO1E were identified and all of them were published in single nucleotide polymorphism database from national center for biotechnology information. Furthermore, all the 10 MYO1E mutations were in heterozygous states.

CONCLUSIONMYO1E mutations are not a major cause of Chinese children with sporadic SRNS in the study.

Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; China ; ethnology ; DNA Mutational Analysis ; Ethnic Groups ; genetics ; Exons ; Female ; Humans ; Infant ; Male ; Mutation ; genetics ; Myosin Type I ; genetics ; Nephrotic Syndrome ; congenital ; ethnology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic