OBJECTIVE To study the pharmacokinetic characteristics of ciprofol in pregnant and fetal rats， and provide reference for the application of ciprofol in cesarean section. METHODS Eight pregnant rats were selected. A single dose of 2.4 mg/kg of ciprofol was administered via the tail vein. One fetal rat was selected at 2， 4， 8， 12， 16， 25， 35， 45， 60， and 90 minutes respectively after ciprofol administration. Subsequently， whole blood samples were collected simultaneously from both the pregnant rats and fetal rats. HPLC-MS/MS method was used to determine the concentration of ciprofol in the bodies of pregnant and fetal rats. The ratios of fetal-to-maternal blood concentrations （F/M ratios） at each time point were calculated， and the F/M-time curves were plotted. Subsequently， non-compartmental pharmacokinetic parameters were computed using DAS 2.0 software. RESULTS Compared with pregnant rats， cmax， AUC0-90 min and AUC0-∞ of ciprofol in fetal rats were decreased significantly， while MRT was increased significantly （P＜0.05）. The F/M curve of ciprofol initially increased and then decreased， and between 0.16- 0.84， reaching a maximum value of 0.84 at 45 minutes. CONCLUSIONS Ciprofol can penetrate the placental barrier， and there are significant differences in pharmacokinetic parameters between pregnant and fetal rats. Moreover， the exposure level of ciprofol in fetal rats is much lower than that in pregnant rats. Therefore， ciprofol shows promise as an ideal anesthetic agent for cesarean section delivery.

OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules （NEPA） on the pharmacokinetics of Paclitaxel for injection （albumin bound） （i. e. albumin-bound paclitaxel） under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group （n＝16）. Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling， intestinal microbiota diversity was analyzed， and the mRNA expressions of cytochrome P450 3A1 （CYP3A1） and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above （n＝16）. The normal group was subdivided into the TP chemotherapy group （TP-1 group） and the TP chemotherapy+NEPA group （TP+NEPA-1 group）； the model group was subdivided into the TP chemotherapy group （TP-2 group） and the TP chemotherapy+NEPA group （TP+NEPA-2 group） （n＝8）. Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension （25.8 mg/kg， calculated by netupitant）. One hour later， all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard， plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group， the model group showed significantly decreased Chao1 and Shannon indexes （P＜0.05）， significant alterations in microbiota composition and relative abundance， and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues （P＜0.05）. Compared with the TP-1 group， the AUC0－t， AUC0－∞， MRT0－t of paclitaxel in the TP-2 group， the cmax， AUC0－t， AUC0－∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged； CL of paclitaxel in the TP-2 group， Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened （P＜0.05）. Compared with the TP-2 group， cmax of paclitaxel in the TP+NEPA-2 group was significantly increased， and Vd and MRT0－t were significantly decreased or shortened （P＜0.05）. CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11， leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However， under conditions of intestinal microbiota disorder， concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.

Objective To explore the immune mechanism of Tibetan medicine Twelve Flavors Yishou San in intervening with acute lung injury.Methods Construct a lipopolysaccharide(LPS)-induced acute lung injury rat model and treated it with Twelve Flavors Yishou San.The intervention effect of Twelve Flavors Yishou San on LPS induced acute lung injury was determined through lung pathological sections and blood gas analysis.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression of pro-inflammatory cytokine tumor necrosis factor-α(TNF-α)and anti-inflammatory cytokine interleukin(IL)-10 in rat's bronchoalveolar lavage fluid.Flow cytometry was used to detect changes in immune cells in rat's bronchoalveolar lavage fluid,lungs,spleen and peripheral blood.Results LPS successfully induced an acute lung injury model in rats,and Twelve Flavors Yishou San could alleviate the exudation of inflammatory cells,elevated oxygen partial pressure in LPS induced acute lung injury to varying degrees.The ELISA results of rat bronchoalveolar lavage fluid showed that compared with normal control group,the TNF-α level in the bronchoalveolar lavage fluid of rats with acute lung injury was increased and the IL-10 level was decreased,while the Twelve Flavors Yishou San could alleviate this effect.The results of flow cytometry showed that Twelve Flavors Yishou San could significantly reduce neutrophil infiltration in rat bronchoalveolar lavage fluid,but had no significant effect on macrophages and adaptive immune response.Conclusion Twelve Flavors Yishou San can alleviate LPS induced acute lung injury by inhibiting neutrophil infiltration,providing an important experimental basis for fully understanding the therapeutic mechanism of Twelve Flavors Yishou San.

The WUSCHEL related-homeobox (WOX) family is one of the plant-specific transcription factor families, playing important roles in plant growth and development. In this study, 51 WOX gene family members were identified from the genome data of Brassica juncea by searching and screening with HUMMER, Smart and other software. Their protein molecular weight, amino acids numbers, and isoelectric point were analyzed by using Expasy online software. Furthermore, bioinformatics software was used to systematically analyze the evolutionary relationship, conservative region, and gene structure of the WOX gene family. The mustard WOX gene family was divided into three subfamilies: ancient clade, intermediate clade, and WUS clade/modern clade. Structural analysis showed that the type, organization form and gene structure of the conservative domain of WOX transcription factor family members in the same subfamily were highly consistent, while there was a certain diversity among different subfamilies. 51 WOX genes are distributed unevenly on 18 chromosomes of mustard. Most of the promoters of these genes contain cis acting elements related to light, hormone and abiotic stress. Using transcriptome data and real-time fluorescence quantitative PCR (qRT-PCR) analysis, it was found that the expression of mustard WOX gene was spatio-temporal specific, among which BjuWOX25, BjuWOX33, and BjuWOX49 might play an important role in the development of silique, and BjuWOX10, BjuWOX32, and BjuWOX11, BjuWOX23 respectively might play an important role in the response to drought and high temperature stresses. The above results may facilitate the functional study of mustard WOX gene family.
Mustard Plant/genetics* ; Multigene Family/genetics* ; Transcription Factors/metabolism* ; Plants/genetics* ; Promoter Regions, Genetic ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

【Objective】 To learn the production efficient of platelet components among prefecture-level blood stations in China, to provide supporting data for those blood stations to optimize the production mode of platelet components and continuously improve production efficiency and supply capacity. 【Methods】 The data from 2017 to 2020 was obtained from 24 prefecture-level blood stations who were the members of the practice comparison network for blood institutes in China. The collection units of apheresis platelets, the number of dual-collections of apheresis platelets and plasma, the average apheresis units of one platelet apheresis procedure, the discarded rate of apheresis platelets, the amount of expired apheresis platelets and the amount of apheresis platelets issued were collected. For concentrated platelets, the prepared amount of platelet concentrates and the amount of expired platelet concentrates were collected; both the quantity of qualified and issued concentrated platelets were submitted for statistical analysis.The total output and efficiency of platelet components were calculated based on the collected data. 【Results】 The average annual growth rate of apheresis platelets collection in 24 prefecture-level blood stations was 12.23%, accounting for 99.80% of the total platelet output; the average collection unit of one platelets apheresis procedure was 1.75; from 2019 to 2020, only 5 blood stations performed dual-collection of platelet and plasma during one apheresis procedure; the discarded rate of apheresis platelets was 0.28%, of which 0.007% was due to expiration. A total of 1 621.2 therapeutic units of concentrated platelets were prepared, and 13.03% of them was discarded due to the expiration. The production efficiency of platelet components was 97.56%, of which the production efficiency of apheresis platelets was 97.61% and the production efficiency of concentrated platelets was 74.43%. 【Conclusion】 There are large regional differences in the supply capacity of platelet components in prefecture-level blood stations. Apheresis platelets are the main resource of platelet components product, and the collection capacity is increasing over the years with the characteristics of high production efficiency and low expiration scrapping rate. However, the preparation of concentrated platelets are still limited with relatively low production and high expiration discarded rate.

Toxoplasma gondii, an intracellular protozoan parasite that infects one-third of the world’s population, has been reported to hijack host cell apoptotic machinery and promote either an anti- or proapoptotic program depending on the parasite virulence and load and the host cell type. However, little is known about the regulation of human FHs 74 small intestinal epithelial cell viability in response to T. gondii infection. Here we show that T. gondii RH strain tachyzoite infection or ESP treatment of FHs 74 Int cells induced apoptosis, mitochondrial dysfunction and ER stress in host cells. Pretreatment with 4-PBA inhibited the expression or activation of key molecules involved in ER stress. In addition, both T. gondii and ESP challenge-induced mitochondrial dysfunction and cell death were dramatically suppressed in 4-PBA pretreated cells. Our study indicates that T. gondii infection induced ER stress in FHs 74 Int cells, which induced mitochondrial dysfunction followed by apoptosis. This may constitute a potential molecular mechanism responsible for the foodborne parasitic disease caused by T. gondii.

AIM To investigate the effects of safflower yellow on myocardial injury in patients with severe sepsis.METHODS Using prospective research methods,ninety-two patients with severe sepsis treated in our hospital from Jan.2013 to Mar.2016 were divided equally into two groups:control group (routine treatment) and observation group (routine treatment + safflower yellow).In addition,6 and 72 hours after the treatment,heart-type fatty acid binding protein (H-FABP),creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) of patients were detected,and the changes of left ventricular ejection fraction (LVEF) and sequential organ failure assessment (SOFA) scores were observed;length of ICU stay,cumulative incidence of major adverse cardiac events (MACE) and 28-day survival also were recorded at the same time.RESULTS In admission,there were no differences in the levels of H-FABP,CK,CK-MB and LVEF,SOFA scores between the two groups.After 6 hours treatment,the levels of H-FABP,CK,CK-MB and SOFA score in the observation group were lower than those in the control group;the two groups had higher levels of H-FABP,CK and CK-MB than those before the treatment,SOFA score was lower than that before the treatment;After 72 hours treatment,H-FABP,CK,CK-MB and SOFA score were lower than those after 6 hours treatment;SOFA score in the observation group was lower than that in the control group;there were no differences in H-FABP,CK and CK-MB between the two groups.The observation group had a lower cumulative incidence of MACE than the control group.There was no statistical difference in LVEF and length of ICU stay after the treatment between the two groups.The observation group had a higher 28-day survival than the control group,the difference was statistically significant (76.08％,35/46 vs 54.35％,25/46;x2 =4.529,P =0.033).The level of serum H-FABP in severe sepsis patients was negatively correlated with LVEF (r =-0.270,P =0.009).CONCLUSION Therapeutic effects of safflower yellow on myocardial injury in patients with severe sepsis is superior to routine treatment with the improvement of the prognosis of patients to a certain extent.

Objective The aim of this study was to investigate the relationship between serum C-reactive protein (CRP) and muscle strength, physical performance in the elderly. Methods A cross-sectional study was conducted in Hangu district of Tianjin from April to June in 2013. Totally 1 131 subjects aged 60 years or older completed the survey. Every subject filled out a standard questionnaire and underwent grip strength test, timed up and go test (TUGT). Serum CRP concentrations were determined using chemiluminescent immunoassay kits. Multivariate analysis was performed to determine the relationship between CRP and muscle strength, physical performance. Results After adjustment for potential confounding factors including age, BMI, smoking status, drinking status, hypertension, diabetes, cardiovascular disease, anemia, cancer and physical activity, the multiple linear regression analysis suggested that CRP levels were inversely related to handgrip strength (β'=-0.11, P<0.01), and the logistic regression analysis showed that compared with subjects in the lowest quintile, the odds ratios and 95%confidence interval of higher quintile of CRP were 1.09 (0.50, 2.39) and 2.70 (1.34, 5.66) (Ptrend<0.05) in males. However, the relationship between CRP and muscle strength, physical performance was not statistically significant in females. Conclusions In males, higher serum CRP levels were independently correlated with lower muscle strength and poor physical performance in older adults. These results suggested that inflammation-signaling pathways may play an important role in the progression of sarcopenia.

Objective Neutrophil/lymphocyte ratio (NLR) is a simple and reliable inflammation biomarker but few studies have assessed the relationship between NLR and hypertension in Chinese population. In order to evaluate how NLR is related to the incidence of hypertension, we designed a large scale prospective cohort study in an adult population. Method Participants were recruited from Tianjin Medical University's General Hospital?Health Management Centre. Hypertension?free subjects (men, 13 638;women,15 212) were followed up for a median of 2.7 years. Adjusted Cox proportional hazards regression models were used to assess relationships between the quintiles of NLR and the incidence of hypertension. Result During the follow-up period, 1 348 subjects in men and 476 subjects in women developed hypertension. The hazard ratios of hypertension incidence were evaluated in increasing NLR quintiles both in men and women. In the final multivariate models, the hazard ratios (95% confidence interval) for hypertension across NLR quintiles were 1.00 (Reference), 1.05 (0.87, 1.26), 1.02 (0.85, 1.22), 1.07 (0.90, 1.29) and 1.22 (1.03, 1.45) (P for trend=0.01), in men;1.00 (Reference), 1.11 (0.82, 1.49), 0.79 (0.58, 1.08), 1.13 (0.85, 1.52) and 1.25 (0.94, 1.66) (P for trend=0.07), in women, respectively. Conclusion This study showed that the elevated NLR levels were significantly related to an increased risk of developing hypertension in men, but not in women.

Objective To assess the therapeutic effect of bone marrow‐derived mesenchymal stem cells (BMSCs) on osteoporotic fracture healing .Methods Bone marrow of the rat bilateral femur and tibia bone tissue were collected ,and BMSCs were isolated by the whole bone marrow adherence method .Sixty female 11‐week‐old SD rats were ovariectomized (OVX) to induce osteoporosis followed by bilateral fracture generation .Twenty rats were left without giving any further treatment (OVX controls) ,20 received injection of saline (OVX+placebo control) and 20 were given injection of BMSCs (OVX+BMSCs) .X‐ray scan was performed at 3‐day ,4‐week and 8‐week post‐fracture ,respectively .Results Flow cytometry analysis revealed that the isolated BMSCs express sur‐face antigens similar to those reported previously .X‐ray results showed that compared with OVX and OVX+placebo groups ,BM‐SCs treatment markedly accelerated fracture healing of in osteoporotic rats .Conclusion Transplantation of BMSCs can effectively improve the healing of primary osteoporotic fracture .