The polymorphism and thermostability of nirmatrelvir, the main antiviral component of the oral COVID-19 treatment drug, were studied. Four polymorphs of nirmatrelvir were prepared by recrystallization methods. Among them, Form 1 and nirmatrelvir methyl tert-butyl ether solvate (Form 2) had been reported in the literature, while nirmatrelvir isobutyl acetate solvate (NMTW-IBAC) and nirmatrelvir ethyl acetate solvate (NMTW-EA) are two new solvates. The crystal structures were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The thermostability of polymorphism and crystalline transformation were also investigated by combining Hirshfeld surface analysis and interaction energy analysis. The results showed that nirmatrelvir Form 1 belongs orthorhombic crystal system with the space group P2₁2₁2₁ and one nirmatrelvir molecule included in the asymmetric unit, which has the same crystal structure as nirmatrelvir Form 4 reported in the literature. Owing to its larger thermal expansion, the differences in crystallographic parameters obtained at different temperatures were found between Form 1 and Form 4. Three solvates of nirmatrelvir belonged to the iso-structural with monoclinic crystal system and the space group P2₁, in which the asymmetric unit contains one nirmatrelvir molecule and one solvent molecule. The thermal analysis results showed that nirmatrelvir Form 1 was a solvent-free crystal form with the best thermal stability and the strongest intermolecular hydrogen bonding. Among the three solvates, NMTW-EA has the worst thermal stability and the weakest hydrogen bonding interaction between the nirmatrelvir molecule and the solvent molecule. The energy framework of nirmatrelvir solvates showed that the closer the arrangement between solvent and nirmatrelvir molecules, the greater the total interaction energy between solvent and nirmatrelvir molecules. The phase transition studies of the three solvates showed that NMTW-IBAC and NMTW-EA were transformed into amorphous after desolvation, respectively, while Form 2 undergoes oiling during desolvation. The research provides theoretical guidance for the analysis, identification and quality control of nirmatrelvir polymorphs.

Objective To discuss the effect of homemade oxygen gasbag on ICU patients with scrotal edema.Methods Seventy-two ICU patients with scrotal edema,in which 60 cases had erythema,peeling and seepage,were chosen and divided into the observation group and the control group,each with 36 cases.The observation group received treatment of air inflation by oxygen gasbag while the control group received treatment of infrared radiation and hydropathic compress of 33％ MgSO4.Both groups also received active treatment of primary disease,nutrition improvement,hypoalbuminemia rectifying,pain control and anxiety relief.Effects of two groups were compared.Results Effect on scrotal edema patients was better in the observation group than in the control group.There were 26 cases (72.7％) who had excellent effects,9 cases (25.0％) who had effects and 1 case (2.7％) who had no effect in the observation group,and there were 19 cases (52.7％) who had excellent effects,8 cases (22.2％) who had effects and 9 cases (25.0％) who had no effect in the control group.The difference was statistically significant (x2 =7548,P =0.023).The effect on patients with scrotal edema,erythema,peeling and seepage was also better in the observation group than in the control group,and the difference was statistically significant (x2 =9.977,P =0.007).Conclusions Homemade oxygen gasbag is a safe,effective,simple,economical and comfortable way to treat scrotal edema,which is worthy of clinical promotion.

Objective To explore the influencing factors on short -term efficacy of intravenous thrombolysis with rt -PA.Methods The clinical data of the 95 acute ischemic stroke(AIS)patients who received thrombolytic therapy were analyze.Multivariate logistic regression analysis was used to determine the possible influencing factors. Results Fifty -six(58.95%)patients had favourable outcomes after thrombolytic therapy for 24 hours.Multivariate logistic regression analysis indicated that diabetes(OR =3.933,95% CI 1.199 ~12.897)and TOAST classification (OR =1.448,95% CI 1.032 ~2.032 )were the independent predictors of short -term outcome.Conclusion Diabetes and TOAST classification are the major influencing factors of short -term efficacy after intravenous thrombolysis with rt -PA.It should pay attention screening patients for intravenous thrombolysis therapy and predicting the efficacy of thrombolysis.

Objective To discuss the application of post quantification inspection in nursing quality management in ICU of Siehuan cancer hospital. Methods According to the nursing quality criteria, work specification and different requirements in each post and weighted value of each post, quantification inspection regulations and score standardization were formulated and brought into effect in each post. Results After theapplication of post quantification inspection, the nursing service quality and patients' satisfaction to nursingservice were improved. This method could scientifically embody the quality of nursing work, and alsoconsummated the head nurses' administration, thereby improving the professional level of nurses to some extent.Conclusions The application of post quantification inspection enhances the science and operation of nursingmanagement, and helps to improve the level of nursing management.

Objective To evaluate the effectiveness of blood gas analysis in samples from two regions.Methods 112 patients with APACHE Ⅱ scores 27 ～ 43 were taken arterial blood from dorsalis pedis artery and femoral artery respectively. Compare the clinical effect of the samples. Results There is no statistically significant difference between results of two blood collection methods ( P ＞ 0. 05 ), While there is statistically significant difference in puncture success ( 110 vs 100, χ2 = 14.23, P ＜ 0. 05 ), vein mistaken injury, hematoma formation, thrombosis, and compression time ( 12 vs 1,7 vs 0,6 vs 0,5.5 ±0.7 vs 2.5 ±0.5 ;χ2 =9.32,5.99,4.85,t = 38. 06, P ＜ 0. 05 ). Conclusions Blood collection method should be determined by the different situation of critically ill patients. Femoral artery blood sample should be taken with caution in order to prevent complication and improve quality of nursing care.

To study the relationship between hematopoiesis and primordial germ cells, chick embryos at different developing stages were flatbed and located. After fixed by glutaral, the embryos were PAS and HE stained respectively, dehydrated serially, transparent, mounted, and were observed in situ or in cut sheet condition. The results showed: (1) the cellule amorphous and the disposition in chick embryo of PGCs were coincident no matter stained by PAS or HE staining, and HE staining could disclose the morphologic characteristics more clearly, exactly and completely; (2) genesis of blood island could be observed at the boundary of light and dark region of the extraembryonic blastoderm at about 26 hours; (3) both the blood vessel endothelium cells and free cells of the blood island were differentiated from PGCs. The generating of genuine yolk sac was at about 44 - 48 hours. It is concluded that the initial anatomic site of blood island genesis may be is mesoblast of extraembryonic blastoderm rather than the yolk sac; the blood vessel endothelium cells and the blood cells are generated parallel; the PGCs are the common ancestry of angioblast and HSC.
Animals ; Cell Differentiation ; Cell Movement ; Cells, Cultured ; Chick Embryo ; cytology ; Hematopoietic System ; cytology

The purpose of this study is to investigate the applicability of a natural swelling matrix derived from boat-fruited sterculia seed (SMS) as the propellant of osmotic pump tablets. The sugar components, static swelling, water uptake and viscosity of SMS were determined and compared with that of polythylene oxide (WSR-N10 and WSR-303). Both ribavirin and glipizide were used as water-soluble and water-insoluble model drugs. Then, the monolayer osmotic pump tablets of ribavirin and the bilayer osmotic pump tablets of glipizide were prepared using SMS as the osmotically active substance and propellant. SMS was mainly composed of rhamnose, arabinose, xylose and galactose and exhibited relatively high swelling ability. The area of the disintegrated matrix tablet was 20.1 times as that at initial after swelling for 600 s. SMS swelled rapidly and was fully swelled (0.5%) in aqueous solution with relative low viscosity (3.66 +/- 0.03) mPa x s at 25 degrees C. The monolayer osmotic pump tablets of ribavirin and the bilayer osmotic pump tablets of glipizide using SMS as propellant exhibited typical drug release features of osmotic pumps. In conclusion, the swelling matrix derived from boat-fruited sterculia seed, with low viscosity and high swelling, is a potential propellant in the application of osmotic pump tablets.
Arabinose ; chemistry ; isolation & purification ; Chemistry, Pharmaceutical ; Delayed-Action Preparations ; Drug Carriers ; Galactose ; chemistry ; isolation & purification ; Glipizide ; administration & dosage ; chemistry ; Osmosis ; Plants, Medicinal ; chemistry ; Rhamnose ; chemistry ; isolation & purification ; Ribavirin ; administration & dosage ; chemistry ; Seeds ; chemistry ; Solubility ; Sterculiaceae ; chemistry ; Tablets ; Technology, Pharmaceutical ; methods ; Viscosity ; Water ; Xylose ; chemistry ; isolation & purification

In this paper, chloramphenicol was selected as a model drug to prepare in situ gels. The intrinsic dissolution rate of chloramphenicol from in situ gel was evaluated using the surface dissolution imaging system. The results indicated that intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel decreased significantly when the poloxamer concentration increased. The addition of the thickener reduced the intrinsic dissolution rate of chloramphenicol thermosensitive gel, wherein carbomer had the most impact. Different dilution ratios of simulated tear fluid greatly affected gel temperature, and had little influence on the intrinsic dissolution rate of chloramphenicol from the thermosensitive in situ gel. The pH of simulated tear fluid had little influence on the intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel. For the pH sensitive in situ gel, the dissolution rates of chloramphenicol in weak acidic and neutral simulated tear fluids were slower than that in weak alkaline simulated tear fluid. In conclusion, the intrinsic dissolution of chloramphenicol from in situ gel was dependent on formulation and physiological factors. With advantages of small volume sample required and rapid detection, the UV imaging method can be an efficient tool for the evaluation of drug release characteristics of ophthalmic in situ gel.
Acrylic Resins ; chemistry ; Anti-Bacterial Agents ; administration & dosage ; chemistry ; Chloramphenicol ; administration & dosage ; chemistry ; Drug Delivery Systems ; Gels ; chemistry ; Hydrogen-Ion Concentration ; Ophthalmic Solutions ; chemistry ; Poloxamer ; chemistry ; Solubility ; Spectrophotometry, Ultraviolet ; Temperature ; Viscosity

OBJECTIVEThe purpose of this study was to assess the feasibility of fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), that could be taken up by breast cancer cells highly expressing glucose transporter 1 (GLUT-1). The purpose of this study was to clarify if a fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), can be taken up by breast cancer cells highly expressing glucose transporter 1 (GLUT-1), and to assess whether it can be used as a targeting imaging agent.

METHODSThe expressions of GLUT-1 mRNA and protein in breast cancer MDA-MB-231 cells were detected by RT-PCR and immunohistochemistry, respectively. The difference of GLUT-1 protein expression between breast cancer MDA-MB-231 cells and MCF-7 cells was compared by Western blot. Secondly, MDA-MB-231 cells which were grown in 6-well plates were incubated with 2-NBDG, and the result of 2-NBDG uptake was analyzed by fluorescence microscopy and flow cytometry. The difference of 2-NBDG absorption in MDA-MB-231 and MCF-7 cells was compared by flow cytometry.

RESULTSThe results of RT-PCR and immunohistochemistry confirmed that MDA-MB-231 cells highly expressed GLUT-1. Furthermore, Western blot revealed that GLUT-1 expression of MDA-MB-231 cells (0.946 ± 0.007) was higher than that in the MCF-7 cells (0.833 ± 0.010). Fluorescence microscopic and flow cytometric analysis showed that 2-NBDG was uptaken rapidly by MDA-MB-231 cells. Addition of 50 mmol/L D-glucose to the media with 2-NBDG reduced its uptake by 46.0%. Moreover, flow cytometry indicated that the fluorescence intensity of MDA-MB-231 cells (25.10 ± 0.57) was higher than that of MCF-7 cells (10.12 ± 0.62) when incubated with 2-NBDG for 20 minutes.

CONCLUSIONThe preliminary data clearly demonstrate that 2-NBDG is taken up and accumulated in breast cancer cells that highly express GLUT-1, and may be used as an optical probe for glucose uptake in hypermetabolic malignant cells.

4-Chloro-7-nitrobenzofurazan ; analogs & derivatives ; pharmacokinetics ; Blotting, Western ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Deoxyglucose ; analogs & derivatives ; pharmacokinetics ; Female ; Flow Cytometry ; Glucose Transporter Type 1 ; genetics ; metabolism ; Humans ; Immunohistochemistry ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

Objective:To improve the genetic stability of HBV gene in transgenic mice.Methods:HBV transgenic mice were bred by backcross and double cross.The HBV gene expression and replication were studied with real-time PCR,ELISA and chemiluminescence.Results:The HBV transgenic mice have stably bred to 23rd generation.The serum HBsAg level is 4122.31?2044.74IU/ml;The rate of HBV transgenic mice whose serum HBV DNA reach 104~106copies/ml was 93.93%.The HBV replication and expression were improved markedly.There is no difference between male and female mice about serum HBsAg level.Conclusion:After breeding the HBV gene was expressed stably with high-level in transgenic mice.