Base on the Kawakita powder compression equation, a general theoretical model for predicting the compression characteristics of multi-components pharmaceutical powders with different mass ratios was developed. The uniaxial flat-face compression tests of powder lactose, starch and microcrystalline cellulose were carried out, separately. Therefore, the Kawakita equation parameters of the powder materials were obtained. The uniaxial flat-face compression tests of the powder mixtures of lactose, starch, microcrystalline cellulose and sodium stearyl fumarate with five mass ratios were conducted, through which, the correlation between mixture density and loading pressure and the Kawakita equation curves were obtained. Finally, the theoretical prediction values were compared with experimental results. The analysis showed that the errors in predicting mixture densities were less than 5.0% and the errors of Kawakita vertical coordinate were within 4.6%, which indicated that the theoretical model could be used to predict the direct compaction characteristics of multi-component pharmaceutical powders.
Cellulose ; chemistry ; Excipients ; chemistry ; Fumarates ; chemistry ; Lactose ; chemistry ; Models, Chemical ; Powders ; chemistry ; Pressure ; Starch ; chemistry ; Technology, Pharmaceutical

Objective To evaluate the role of interlukin-6 and signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway in the up-regulation of high mobility group box 1 (HMGB1) expression in lung tissues in septic rats.Methods Ninety healthy male Wistar rats,aged 10-14 weeks,weighing 250-300 g,were randomly divided into 3 groups (n =30 each):sham operation group (group S),cecal ligation and puncture (CLP) group and anti-IL-6 monoclonal antibody group (group IL-6).Sepsis was induced by CLP.Anti-IL-6 monoclonal antibody 0.5 mg/kg was injected intraperitoneally 1 h before CLP,while the equal volume of normal saline was given in groups S and CLP.Six rats in each group were sacrificed at 6,12,24,48 and 72 h after CLP and lungs were removed for determination of HMGB1 content (by RT-PCR),HMGB1 mRNA expression (by ELISA) and STAT3-DNA binding activity (by electrophoretic mobility shift assay) in lung tissues.Results Compared with S group,HMGB1 content,HMGB1 mRNA expression and STAT3-DNA binding activity were significantly increased in groups CLP and IL-6 (P ＜ 0.05).HMGB1 content,HMGB1 mRNA expression and STAT3-DNA binding activity were significantly lower in group IL-6 than in group CLP (P ＜ 0.05).Conclusion IL-6/STAT3 signaling pathway is involved in the up-regulation of HMGB1 expression in lung tissues in septic rats.

Objective To observe the dynamic changes of leptin and transforming growth factor (TGF)-β1 in formation of liver fibrosis in rats,and the role of leptin in liver fibrosis.Methods Six rats were served as normal control(0 week)and killed at the beginning of the study.Thirty-two rats were subcutaneously injected with 60%CCl4 to establish fibrotie models.The rats were than sacrificed at 3,6,9 and 12 weeks with eight each.Expressions of leptin mRNA,Ob-Rb mRNA,TGF-β1 mRNA and TGF-βRⅡmRNA in liver were detected by reverse-transcription polymerase chain reaction(RT-PCR).Expression of Smad3 and Smad7 proteins were determined by Western blot.The expression and loealization of leptin,Ob-Rb and TGF-β1 in liver tissue were detected by immunohistochemistry.Results The expression of leptin mRNA,Ob-Rb mRNA,TGF-β1 mRNA and TGF-βR Ⅱ mRNA in 0 week were 0.43±0.45,0.57±0.21,0.19±0.12 and 0.30±0.22,respectively,and increased to 1.27±0.19,1.70±0.29,1.70±1.00 and 2.14±1.02 at 12 weeks(P＜0.05).At the same times the level of Smad3 increased from 0.44±0.24 at 0 week to 1.75±1.05 at 12 weeks.While the expression of Smad7 was decreased from 1.35±0.12 at 0 week to 0.74±1.21 at 12 weeks(P＜0.05).The expressions of leptin,Ob-Rb and TGF-β1 were increased with the formation of the fibrosis(P＜0.01).Conclusions With the development of liver fibrosis,the expressions of leptin,Ob-Rb mRNA and protein are increased and improved the formation of the fibrosis.Its mechanisms may be correlated with up-regulation of TGF-β1,TGF-βR Ⅱ and Smda3 expressions and down-regulaton of Smad7 expression by leptin.

Objective To investigate the effect of propofol on nNOS expression after focal cerebral ischemia-reperfusion in rats and the possible mechanism of protective effect of propofol on brain. Method Seventy-eight male Wistar rats, weighting 250 ~ 300 g, were randomly divided into 3 groups:(1)Sham operation group (S group, n=6) was performed with scham operation; (2) Ischemia-reperfusion group (group I-R, n=36) was subjected to 2-hour right middle cerebral artery occlusion and then reperfusion was followed, saline (1 mg/kg) was injected into the right lateral cerebral ventricle using microsyringe before reperfusion;(3) Propefol group (group P, n=36) was injected with propofol (1mg/kg) into the right lateral cerebral ventricle using microsyringe right after ischemia. Group I-R and group P were divided into 3 subgroups according to the reperfusion time: 1 h, 3 h and 6 h. The neurological function of all rats were tested before reperfusion. The cerebral infarction area of the whole brain was calculated with TIC staining (n=6). The pathological change of brain was observed from HE staining (n=6) and the nNOS protein expression was obtained by immuno- histochemical method (n=6). Results Compared with I-R group, the neurological function was better in group P(P

Objective To investigate the effects of dexmedctomidine pretreatment and postconditioning on renal ischemia-reperfusion (I/R) injury in rats.Methods Thirty-two male Wistar rats,aged 3-4 months,weighing 220-300 g,were randomly divided into 4 groups ( n =8 each):sham operation group ( group S),I/R group,dexmedetomidine pretreatment group (group Pre) and dexmedetomidine postconditioning group (group Post).The rats were anesthetized with phenobarbital sodium 65 mg/kg.Renal I/R was produced by occlusion of both renal pedicles for 60 min followed by 48 h reperfusion.Dexmedetomidine 50 μg/kg was given intraperitoneally at 30 min before ischemia and at the beginning of reperfusion in Pre and Post groups respectively.The concentrations of serum creatinine and blood urea were determined at 0,24 and 48 h of reperfusion (T1-3).The renal tissues were obtained at the end of reperfusion for microscopic examination and detection of apoptosis by TUNEL assay.Acute kidney tubular necrosis was scored and apoptosis index (AI) was calculated.Results Compared with group S,the concentration of serum creatinine and blood urea at T2.3,and acute kidney tubular necrosis score and AI were significantly increased in I/R,Pre and Post groups ( P ＜ 0.05).Compared with I/R group,the concentration of serum creatinine and blood urea at T2.3,acute kidney tubular necrosis score and AI were significantly decreased in Pre and Post groups ( P ＜ 0.05).Conclusion Both dexmedetomidine pretreatment and postconditioning can attenuate renal I/R injury through inhibition of cell apoptosis in rats.

Objective To evaluate the effects of rapamycin combined with rosiglitazone on lung injury in septic rats.Methods One hundred and twenty healthy male Wistar rats were randomly divided into 5 groups (n =6 each):sham operation group (group S); cecum ligation and punture (CLP) group; rapamycin group (group RPM) ; rosiglitazone group (group RGZ) ; rapamycin plus rosiglitazone group (group RPM + RGZ).The rats were anesthetized with intraperitoneal 10% chloral hydrate 100 mg/kg.Sepsis was induced by CLP in groups CLP,RPM,RGZ and RPM + RGZ.At 30 min before CLP,rapamycin 0.4 mg/kg was injected subcutaneously in RPM group,rosiglitazone 0.3 mg/kg was injected via the femoral vein in RGZ group,and rapamycin 0.4 mg/kg was injected subcutaneously and rosiglitazone 0.3 mg/kg was injected via the femoral vein in group RPM + RGZ.While the equal volume of normal saline was given instead in CLP group.Six rats were sacrificed at 2,6,24 and 48 h after CLP in each group,and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under microscope.The pathological changes of lungs were scored.The myeloperoxidase (MPO) activity and signal transducer and activator of transcription 3 (STAT3)-DNA binding activity in lung tissues were measured.Results Compared with group S,the pathological scores,MPO activity and STAT3-DNA binding activity were significantly increased in groups CLP,RPM,RGZ,RPM + RGZ (P ＜ 0.05).The pathological scores,MPO activity and STAT3-DNA binding activity were significantly lower in groups RPM,RGZ and RPM +RGZ than in group CLP,and in group RPM + RGZ than in groups RPM and RGZ (P ＜ 0.05).Conclusion Rapamycin combined with rosiglitazone offers additional benefit to attenuating lung injury induced by sepsis over rapamycin or rosiglitazone alone,and inhibition of activation of STAT3 pathway is involved in the mechanism.

Objective To explore the predictive capability of different methods for difficult la-ryngoscopy and analyze its optimal cutoff value.Methods Three hundred consecutive patients (aged 18-65 years,weighing 42-88 kg,ASA physical status Ⅰ or Ⅱ)scheduled to undergo general anesthe-sia and surgery were invited to participate.Difficult airway assessments were performed by thyromen-tal height (TMH),thyromental distance (TMD),sternomental distance (SMD),modified Mallam-pati test (MMT)and ratio of height and TMD (RHTMD)before anesthetic induction.Cormack-Le-hane (C-L)grade of laryngoscopy view was assessed after induction.Sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV)and accuracy of these tests were calculated. Receiver operator characteristic (ROC)curve of TMH was performed to determine the optimal cutoff value of TMH.Results There were 22 patients diagnosed as difficult airway.Sensitivity,specificity, PPV,NPV and accuracy of TMH were higher than those of TMD,SMD and MMT tests.Sensitivity of RHTMD was lower than that of TMH test,and specificity,PPV,NPV and accuracy of RHTMD were similar to that of TMH.The optimal cutoff value of TMH was 4.9 cm through ROC curve. Conclusion The optimal cutoff value of TMH detecting difficult laryngoscopy was 4.9 cm.Similar to RHTMD,TMH appears to be more effective for prediction of difficult laryngoscopy than TMD, SMD and MMT.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

In order to clarify the metabolism pathways of scandoside methyl ester, the analysis of metabolites profiling in four kinds of liver microsomes was performed by using an ultra-performance liquid chromatography/ electrospray-tandem mass spectrometry (UPLC-ESI-MS). The data obtained from the 0 h-incubation and the 2 h-incubation were compared and analyzed. After incubation, 5 metabolites of scandoside methyl ester were found in rat, Beagles, rhesus monkey and human liver microsome. The results showed that scandoside methyl ester's major metabolic pathway in the liver microsomes is hydrolysis, oxidation and reduction reactions, and there are certain kinds differences between species. The study provides a research base for further research about iridoid compounds in vivo metabolic pathways.
Animals ; Chromatography, High Pressure Liquid ; Dogs ; Esters ; metabolism ; Humans ; Iridoids ; metabolism ; Macaca mulatta ; Microsomes, Liver ; metabolism ; Rats ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo explore the clinical effects of total vertebral column resection combined with anterior mesh cage support in treating severe congenital kyphoscoliosis.

METHODSFrom April 2008 to April 2012,21 patients with severe congenital kyphoscoliosis were treated with total vertebral column resection and internal fixation through posterior approach combined with anterior mesh cage support. There were 8 males and 13 females with an average age of 19.4 years old (ranged from 10 to 35). And 6 cases were thoracic segments deformity,13 cases were thoracolumbar segments and 2 cases were lumbar segments, of them, 2 cases were accompanied with Chairs deformity, 6 cases with diastematomyelia, 4 cases with syringomyelia,and 1 case with neurofibromatosis. According to the Frankel grade system, 3 cases were grade C, 5 cases grade D and 13 cases grade E. Blood loss, operative time, and perioperative complications were recorded. Coronal and sagittal Cobb angle, apical vertebral offset distance, sagittal offset, the relative height of shoulders, razor back deformities were measured and analyzed before and after operation.

RESULTSThe average operative time was 5.2 h (3.5 to 6.5 h) and blood loss was 2,500 ml (1,400 to 4,900 ml). The 2nd day after operation, apical vertebral offset distance, sagittal offset, the relative height of shoulders, razor back deformities had obviously improved than preoperative (P < 0.05). There was no significant difference in above items between postoperative on the 2nd day and final follow-up (P > 0.05). The corrective rate of kyphosis and scoliosis were (60.97 +/- 6.30)% and (62.24 +/- 5.82)%, respectively. On the first day after surgery,2 cases of Frankel grade E aggravated to grade D, and obtained recovery at 2 week after conservative treatment. And 1 case palinesthesia later,grade D aggravated to grade C and obtained recovery after revision surgery in time. One case complicated with permanent blindness of left eye, 1 case occurred injury of pleura and 2 cases had cerebrospinal fluid leak during operation. All patients were followed up from 9 to 31 months with an av- erage of 18.6 months. At final follow-up,all patients obtained bone union, Frankel grade D in 4 cases and grade E in 17 cases, no correction loss and internal fixation loosening was found.

CONCLUSIONTotal vertebral column resection combined with anterior mesh cage support can effectively correct kyphosis and scoliosis in severe congenital kyphoscoliosis and can avoid injury of spine cord by spinal crispation, but intraoperative position and neurologic complications should still be considered.

Adolescent ; Adult ; Child ; Female ; Humans ; Kyphosis ; complications ; congenital ; diagnostic imaging ; surgery ; Male ; Retrospective Studies ; Scoliosis ; complications ; congenital ; diagnostic imaging ; surgery ; Spine ; surgery ; Tomography, X-Ray Computed ; Young Adult