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.

Professor LI Zhidao puts forward the application of "group acupoints" in his clinical practice by imitating the mutual reinforcement and mutual assistance of Chinese herbal medicine. It is based on the theory as "where is the acupoint located, what are the indications of this acupoint"; and consists with the specific actions of ancient needling techniques at acupoints. The distribution of "group acupoints" is in line with the "located by the region division of the head and trunk, and by the meridians on the four extremities", which is recorded in Zhenjiu Jiayi Jing (the Systematic Classic of Acupuncture and Moxibustion). It shows "the importance of the relationship between acupoints and zangfu", and "the emphasis on the distribution of nerves and muscles" respectively. In clinical practice, controlling needling sensation is the essence of this technique at "group acupoints", the integration of acupoints and needling technique is the basic requirement, and the step-by-step needling manipulation is critical for obtaining the therapeutic effect. "Group acupoints" combined with specific needling technique advance the application efficiency and the effect of acupoints.
Acupuncture Points ; Acupuncture Therapy/methods* ; Humans ; China ; History, 20th Century ; Meridians ; Medicine in Literature ; Acupuncture/history*

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

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.

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 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 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 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 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.