ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time， quasi-molecular ion peaks， secondary fragmentation ions， and literature reports， and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract， the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds， including 21 phenolic acids， 23 diterpenes， 6 flavonoids， 7 organic acids， 3 volatile oils and 13 others， were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma， the major metabolic pathways included reduction， hydration， hydroxylation， demethylation， methylation， sulfation and others， these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones， which may be the material basis of the efficacy. This study can provide reference for pharmacological research， quality control， and clinical application of Danshenyin.

Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?

As a new clinical trial mode,decentralized & digitalized clinical trial(DCT)is based on digital health equipment and uses internet and artificial intelligence technologies to complete the screening,registration,randomization,intervention,evaluation and follow-up of subjects,which is helpful to improve efficiency and reduce trial costs.The DCT mode has been applied to evaluate the treatment and management effects of cardiovascular diseases such as atrial fibrilla-tion,heart failure,coronary heart disease,and hypertension,showing broad development prospects and application space.This article will provide a brief introduction to representative DCT in the global cardiovascular disease field,and look for-ward to the application prospects of this model,providing reference and guidance for accelerating the development of cardio-vascular DCT in China.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Objective:To analyze the phenotype and genotype of two propositi with inherited hypodysfibrinogenaemia caused by compound heterozygous mutations, and investigate the molecular mechanism.Metheds:Two propositi and their family members(7 person in 3 generations and 10 person in 3 generations,respectively) were investigated. The activity of plasma fibrinogen (Fg:C) and thrombin time (TT) were analyzed by coagulation method, the antigen of plasma fibrinogen (Fg:Ag) was detected by immunoturbidimetry. All of the exons and flanking sequences of FGA,FGB,FGG of two propositi were amplified by PCR, followed by direct sequencing. The ClustalX-2, 1-win software was used to analyze the conservatism of mutated gene locus. PROVEAN and Mutation Taster were applied to analyze the pathogenicity of mutated amino acid. The changes of the protein spatial structure and intermolecular interaction were analyzed by Pymol.Results:Fg:C and Fg:Ag of proposita A and B were both significantly decreased (0.74 and 0.78 g/L, 0.96 and 0.94 g/L, respectively). Gene analysis revealed that proposita A and B both carried a heterozygous mutation c.2185G>A(p.AαGlu710Lys) in exon 6 of FGA. Furthermore, proposita A also carried a heterozygous mutation c.701G>T(p.γTrp208Leu) in exon 7 of FGG, and proposita B carried a heterozygous mutation c.1015A>C(p.γSer313Arg) in exon 8 of FGG. Phylogenetic analysis suggested that p.AαGlu710,p.γTrp208 and p.γSer313 were highly conserved among homologous species. All variants were predicted to be deleterious by two online bioinformatic softwares. The protein model analysis indicated that protein spatial structure and intermolecular hydrogen bonds were changed by these variants, which destroyed the stability of Fg.Conclusion:The compound heterozygous mutations of p.AαGlu710Lys and p.γTrp208Leu,p.AαGlu710Lys and p.γSer313Arg might account for the hypodysfibrinogenemia in two propositi.

Objective To validate whether the expression of human cluster of differentiation 55 (hCD55) protein in porcine islet cells could inhibit the activation of complement components in human serum. Methods Four adult pigs with WT (wild type), GTKO [α-1, 3-galactosyltransferase (GGTA1) knockout], GTKO/hCD55 and hCD55 genotypes were selected. Islet cells were isolated from WT, GTKO and GTKO/hCD55 pigs, and the purity and insulin secretion function were detected. The expression of hCD55 at the DNA, RNA and protein levels was analyzed by agarose gel electrophoresis, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry, respectively. Complement-dependent cytotoxicity assay and complement deposition assay were performed under the incubation conditions with fresh human serum. Results The purity of isolated porcine islet cells from three genotype pigs was > 75%, and the glycemic index was > 1. The expression of hCD55 messenger RNA(mRNA) and protein in GTKO/hCD55 porcine islet cells decreased the deposition of human complement component C3c and membrane-attacking complex C5b-9, and reduced the cytotoxicity. Conclusions The expression of hCD55 protein in porcine islet cells could inhibit the activation of human complement and reduce complement-mediated killing effect, indicating that hCD55 protein could exert complement protection effect on porcine islet cells. These findings provide theoretical basis for the application of hCD55 in islet xenotransplantation.

Objective To evaluate the changes in expression of cold-inducible RNA-binding protein (CIRP) in hippocampus during brain injury in a rat model of cardiac arrest-cardiopulmonary resuscitation.Methods Seventv-two clean-grade healthy male Sprague-Dawley rats,weighing 280-350 g,aged 8-10 weeks,were divided into 2 groups using a random number table:sham operation group (S group,n=18) and ischemia-reperfusion group (I/R group,n=54).Tracheal intubation was performed and artery and veins were punctured in group S.Ventricular fibrillation was induced by transoesophageal cardiac pacing to establish the model of cardiac arrest in group I/R.Rats were sacrificed at 12,24 and 48 h after resuscitation and the hippocampus was harvested for determination of CIRP,tumor necrosis factor-alpha (TNF-α) and interleukin-lbeta (IL-1β) protein and mRNA expression (by quantitative polymerase chain reaction or Western blot) and for determination of pathological changes of hippocampi (with a light microscope).Results Compared with group S,the expression of CIRP mRNA in hippocampus was up-regulated at 24 and 48 h after resuscitation,the expression of TNF-α mRNA was up-regulated at 12,24 and 48 h after resuscitation,the expression of IL-1β mRNA was up-regulated at 12 and 24 h after resuscitation,and the expression of CIRP,TNF-α and IL-1β was up-regulated at 12,24 and 48 h after resuscitation in group I/R (P＜0.05).Pathological changes in hippocampal CA1 region were found in group I/R.Conclusion The expression of CIRP in hippocampus is up-regulated,which promotes central inflammatory responses during brain injury in a rat model of cardiac arrest-cardiopulmonary resuscitation.

Objective The purpose of this study was to assess the safety of carbon dioxide pneumoperitoneum on patients during robotic rectectomy.Methods 50 patients [American Society of Anesthesiologists (ASA) physical status Ⅱ,18 and 65 years of age] underwent rectal cancer surgery were selected in our study.According to whether or not robotic assisted surgery was performed,they were divided into a robotic surgery group (group RS) and a laparoscopic surgery group (group LS) by surgical approach,25 patients in each group.All participants were given the same anesthesia protocol.Arterial blood samples 1 ml was obtained from the left radial artery for blood gas analysis to measure the partial pressure of arterial carbon dioxide (PaCO2) and and calculate the arterial-to-end-tidal carbon dioxide pressure difference (Pa-ETCO2) just 10 min after endotracheal intubation (T0),at 30 min(T1),1 h(T2),2 h(T3) after pneumoperitoneum and 30 minutes after release (T4).Meanwhile,the airway peak pressure was monitored.Blood samples (4 ml) extracted at T0,T3 and T4 were centrifuged and measured the serum levels of interleukin (IL)-6 and IL-10 by enzyme linked immunosorbent assay (ELISA).The time to resuscitation,extubation time,intraoperative medication and perioperative adverse events were all recorded.Results Compared with group LS,PaCO2 in the RS group was increased significantly at T1,T2 and T3 after pneumoperitonum and the IL-6 was lower at T4 (P ＜ 0.05).There were no statistically significant differences in Pa-ETCO2,airway peak pressure,IL-10,time to resuscitation,extubation time and the incidence of adverse events between the two groups (P ＞ 0.05).Conclusions It is safe for normal adult patients performed by intravenous anesthesia during robotic-assisted rectal surgery and the inflammatory response is small,which is beneficial to the patient's postoperative recovery.

Objective To explore the effects of microwave irradiation on the proliferation of keloid-derived fibroblasts so as to analyze the expression of collagen-1 and the activation of the signaling pathway involved.Methods Cells from a human keloid scar were cultured in vitro and randomly divided into a control group withont any intervention,a 10 mW/cm2 microwave irradiation (10-MI) group and a 20 mW/cm2 microwave irradiation (20-MI) group.Aliquots of the latter 2 groups were irradiated at their corresponding intensities for 5 min,15 min and 30 min.The growth of fibroblasts was evaluated using MTT assay.The expression of collagen-1 and changes in the phosphorylation of protein JNK were detected using western blotting.Results Compared with the control group,no significant differences in the average growth of the keloid-derived fibroblasts were observed in the 10-MI group,but significant differences were observed in the 20-MI group and among the three sub-groups irradiated for different durations.The expression of type 1 collagen was significantly down-regulated after irradiation in a time-dependent manner.After microwave radiation at 20 mW/cm2,JNK was significantly activated compared to the control group at the different time points.Conclusions Microwave irradiation at 20 mW/cm2 can significantly inhibit the proliferation of keloid-derived fibroblasts and the down-regulalion is correlated with the irradiation's duration.It can also significantly inhibit collagen-1 expression and relieve scar formation through activating the JNK signal pathway.

Objective To observe the effect of continuous incision infusion different concentra-tion of ropivacaine for postoperative analgesia after radical mastectomy.Methods One hundred pa-tients under radical mastectomy,aged 40-70 years,ASA Ⅰ or Ⅱ,were randomly divided into four groups (n =25 each):0.2% (group R1),0.3% (group R2),0.4% (group R3)ropivacaine incision continued infiltration group and patient-controlled intravenous analgesia (group PCIA)as control group.VAS pain scores,sedation Ramsay score and side effects were recorded at each time point in rest and turning over 90°,2 h (T1 ),4 h (T2 ),8 h (T3 ),12 h (T4 ),24 h (T5 ),48 h (T6 )after the operation.Results VAS scores in group R1 at T1-T6 in rest and turn over 90°were significantly high-er than that of group PCIA (P <0.05).There were no significant differences among the group PCIA, group R2 and group R3.Sedation score in PCIA group was significantly higher than that in the other three groups (P <0.05),and the adverse reactions,such as nausea and vomiting,in group PCIA (2 cases)were more serious than that in the other groups (0 cases ).There were no significant differences among the other groups.Conclusion Ropivacaine plays an effective role in infiltration an-algesia when its concentration reaches 0.3% subcutaneous after radical mastectomy.