Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Diagnostic value of lung ultrasound in diagnosing postoperative atelectasis, pleural effusion and pneumothorax in adult patients: a systematic review and meta-analysis / 中华麻醉学杂志

Objective:To systematically evaluate the diagnostic value of lung ultrasound (LUS) in diagnosing postoperative atelectasis, pleural effusion and pneumothorax in adult patients.Methods:PubMed, Embase, Cochrane Library, Web of Science, Wanfang Database, China Science and Technology Journal Database and China National Knowledge Infrastructure were searched for studies comparing the accuracy of LUS Chest radiograph (CXR) or computed tomography (CT) in the diagnosis of postoperative atelectasis, pleural effusion and pneumothorax, and the parameters were the sensitivity and specificity of LUS in diagnosing postoperative atelectasis, pleural effusion and pneumothorax, and the area under the receiver operating characteristic curve (AUC). Analysis was performed using MetaDiSc 1.4, Review Manager 5.4, and STATA 16.0 softewares. CXR and CT were used as standard imaging examination methods, and the combined sensitivity, specificity and AUC of LUS were calculated. Meta regression analysis was conducted on the types of surgeries, standard imaging examination methods (CXR, CT), CXR (CT)/LUS examination intervals (>3 h, ≤3 h), and time points of postoperative LUS examination.Results:Fifteen studies involving 1 585 patients were finally enrolled in the present study. The combined sensitivity of LUS in diagnosing postoperative atelectasis, pleural effusion and pneumothorax was 0.91 (95% confidence interval [ CI] 0.88-0.93), 0.75 (95% CI 0.71-0.78) and 0.53 (95% CI 0.48-0.58), respectively, and the combined specificity was 0.96 (95% CI 0.95-0.97), 0.82 (95% CI 0.81-0.84) and 0.94 (95% CI 0.93-0.95), respectively, and AUC was 0.936 8 ( SE=0.044 2), 0.839 7 ( SE=0.076 7) and 0.914 7 ( SE=0.030 9), respectively. Meta-regression analysis showed that the type of surgery was a source of heterogeneity affecting the diagnosis of pneumothorax by LUS ( P=0.001), and the standard imaging examination method was the source of heterogeneity affecting the diagnosis of pleural effusion by LUS ( P=0.023). Conclusions:Although LUS has a weak ability in detecting non-clinically related pneumothorax (≤3 cm) and a low overall sensitivity in diagnosing postoperative pneumothorax, the specificity is high in adult patients.

Systematic comparison of two kinds of Bufonis Venenum derived from different Bufo gargarizans subspecies based on metabolomics and antitumor activity / 中国中药杂志

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.

Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels / 中国中药杂志

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics / 中国中药杂志

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

Associations between various lipid components and premature myocardial infarction: a cross-sectional study / 中华心血管病杂志

Objective: Hyperlipidemia is closely related to premature acute myocardial infarction (AMI). The present study was performed to explore the correlation between various blood lipid components and the risk of premature AMI. Methods: This is a cross-sectional retrospective study. Consecutive patients with acute ST-segment elevation myocardial infarction (STEMI), who completed coronary angiography from October 1, 2020 to September 30, 2022 in our hospital, were enrolled and divided into premature AMI group (male<55 years old, female<65 years old) and late-onset AMI group. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, lipoprotein (a) (Lp (a)), apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA-1), non-HDL-C/HDL-C and ApoB/ApoA-1 were analyzed. The correlation between the above blood lipid indexes and premature AMI was analyzed and compared by logistic regression, restricted cubic spline and receiver operating characteristic curve (ROC). Results: A total of 1 626 patients with STEMI were enrolled in this study, including 409 patients with premature AMI and 1 217 patients with late-onset AMI. Logistic regression analysis showed that the risk of premature AMI increased significantly with the increase of TG, non-HDL-C/HDL-C, non-HDL-C, ApoB/ApoA-1, TC and ApoB quintiles; while LDL-C, ApoA-1 and Lp (a) had no significant correlation with premature AMI. The restricted cubic spline graph showed that except Lp (a), LDL-C, ApoA-1 and ApoB/ApoA-1, other blood lipid indicators were significantly correlated with premature AMI. The ROC curve showed that TG and non-HDL-C/HDL-C had better predictive value for premature AMI. Inconsistency analysis found that the incidence and risk of premature AMI were the highest in patients with high TG and high non-HDL-C/HDL-C. Conclusion: TG, non-HDL-C/HDL-C and other blood lipid indexes are significantly increased in patients with premature AMI, among which TG is the parameter, most closely related to premature AMI, and future studies are needed to explore the impact of controlling TG on incidence of premature AMI.

Component profile analysis of Sanhan Huashi Formula based on UHPLC-LTQ-Orbitrap-MS, GC-MS, and UHPLC-QQQ-MS/MS / 中国中药杂志

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.

Study on biomarkers of acteoside in treating puromycin aminonucleoside nephropathy in young rats based on non-targeted urine metabolomics technology / 中国中药杂志

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.

Investigation on the pharmacological mechanisms of Shirebi granules in treating gouty arthritis with damp-heat syndrome based on crosstalk of Wnt/β-catenin signaling / 药学学报

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Perioperative mechanical ventilation strategy for COVID-19 patients: Recommendation / 中国胸心血管外科临床杂志

@#Since December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has gradually spread all over the world. With the implementation of class B infectious disease management policy for coronavirus disease 2019 (COVID-19), China has experienced a pandemic. For patients receiving a time-sensitive or emergency surgery, SARS-CoV-2 infection may increase the risk of postoperative pulmonary complications. An appropriate perioperative mechanical ventilation strategy, such as lung protective ventilation strategy, is particularly important for preventing postoperative pulmonary complications in patients undergoing general anesthesia. In addition, how to protect medical personnel from being infected is also the focus we need to pay attention to. This article will discuss the perioperative mechanical ventilation strategy for COVID-19 patients and the protection of medical personnel, in order to provide reference for the development of guidelines.

Membrane dual-targeting probes: A promising strategy for fluorescence-guided prostate cancer surgery and lymph node metastases detection

Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

LncRNA UNC5B-AS1 promotes proliferation and epithelial-mesenchymal transition of cervical cancer cells by regulating Toll-like receptor signaling pathway / 中国药理学通报

Aim To investigate the effects of long non-coding RNA(lncRNA)UNC5B-AS1 on the proliferation and epithelial mesenchymal transformation(EMT)of cervical cancer. Methods GEO and TCGA databases were used to download data sets and differential expression analysis was performed. qRT-PCR was used to verify the differential expression of lncRNA UNC5B-AS1 in normal and cancerous cervical tissues.The interference and overexpression of lncRNA UNC5B-AS1 were transfected into cervical cancer cell lines, and plate cloning, CCK-8 and EdU experiments were used to detect the effect of lncRNA UNC5B-AS1 on the pro-liferation of cervical cancer cells.Transwell assay was used to detect its effect on migration and invasion of cervical cancer cells.The expression levels of EMT-related genes E-Cadherin, N-Cadherin and Vimentin were detected by Western blot. Transcriptome sequencing was used to obtain the signal pathway regulated by lncRNA UNC5B-AS1, and to verify the expression level of related genes. Results RNA microarray and bioinformatics analysis showed that the expression level of lncRNA UNC5B-AS1 in cervical cancer was significantly higher than that in normal cervical tissue, and correlated with the overall survival time of patients.Compared with the negative control group, knockdown lncRNA UNC5B-AS1 could reduce the proliferation, migration and invasion of cervical cancer cells, while overexpression could promote the proliferation, migration and invasion of cervical cancer cells. Western blot showed that lncRNA UNC5B-AS1 could regulate EMT of cervical cancer cells. Transcriptome sequencing showed that lncRNA UNC5B-AS1 could regulate Toll like receptor(TLR)signaling pathway. qRT-PCR and Western blot results showed that the expression levels of TLR-related genes IL-6 and TICAM2 in the knockdown and overexpression lncRNA UNC5B-AS1 group were significantly changed(P<0.05). Conclusions LncRNA UNC5B-AS1 is highly expressed in cervical cancer. Overexpression of lncRNA UNC5B-AS1 may enhance TLR signaling pathway activity, thereby promoting proliferation and EMT of cervical cancer cells.

Meta-analysis of the effect of hollow nail and bone plate on Lisfranc injury / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy of screw and bone plate internal fixation in the treatment of Lisfranc injury.@*METHODS@#The databases of Wanfang, CNKI, Pubmed, EMBASE, VIP, BIOSIS and other databases were retrieved by computer, and the clinical trial literature from January 1, 2000 to August 1, 2021 was retrieved, the methodological quality of the included studies was strictly evaluated and the data were extracted, and the obtained data were meta-analyzed by Revman 5.4 software.@*RESULTS@#Nine randomized controlled trial literature and 10 retrospective cohort studies were included, of which 416 patients in the experimental group were treated with screw internal fixation, and 435 patients in the control group were treated with bone plate internal fixation. Meta-analysis showed that the surgical time of the bone plate internal fixation group was longer than that of the screw internal fixation group [MD=-14.40, 95%CI(-17.21, -11.60), P<0.000 01], the postoperative X-ray anatomical reduction of the bone plate internal fixation group [MD=0.47, 95%CI(0.25, 0.86), P=0.01], the excellent and good rate of postoperative American orthopedic foot and ankle society(AOFAS) foot function score[MD=0.25, 95%CI(0.15, 0.42), P<0.000 01], postoperative AOFAS foot function score [MD=-5.51, 95%CI(-10.10, -0.92), P=0.02] of the bone plate fixation group was better than those of the screw internal fixation group. Two kinds of operation method had no statistical different for postoperative fracture healing time[MD=1.91, 95%CI(-1.36, 5.18), P=0.25], postoperative visual analgue scale(VAS)[MD=0.38, 95%CI(0.09, 0.86), P=0.11], postoperative complications [MD=1.32, 95%CI(0.73, 2.40), P=0.36], the postoperative infection [MD=0.84, 95%CI(0.48, 1.46), P=0.53], the postoperative fracture internal fixation loosening [MD=1.25, 95% CI(0.61, 2.53), P=0.54], the postoperative incidence of traumatic arthritis [MD=1.80, 95%CI(0.83, 3.91), P=0.14].@*CONCLUSION@#Bone plate fixation has better short-term and medium-term results and lower reoperation rate in the treatment of Lisfranc injury, so it is recommended to use bone plate fixation in the treatment of Lisfranc injury.

Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS / 中国中药杂志

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

Association between anesthesia regimen and postoperative infection in patients undergoing cardiac surgery: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective     To evaluate the association between anesthesia regimen (volatile or intravenous anesthetics) and postoperative infection in adult cardiac patients undergoing cardiac surgery. Methods    The clinical data of 496 elective adults undergoing cardiac surgery under cardiopulmonary bypass from June 2019 to June 2020 in West China Hospital of Sichuan University were retrospectively analyzed, including 251 females and 245 males with an average age of 54.1±11.4 years. American Society of Anesthesiologists grade was Ⅰ-Ⅲ. There were 243 patients in a volatile group with sevoflurane or desflurane, and 253 patients in an intravenous anesthesia group with propofol. The primary outcome was the incidence of infection within 30 days after cardiac surgery, including pulmonary infection, surgical site infection, sepsis, and urinary tract infection. The secondary outcomes were duration of mechanical ventilation, incidence of reintubation, ICU stay, postoperative length of hospital stay and total hospitalization cost. Results     A total of 155 (31.3%) patients developed postoperative infection within 30 days, with an incidence of 32.9% in the volatile group and 29.6% in the intravenous anesthesia group. There was no statistical difference in the incidence of infection (RR=1.111, 95%CI 0.855 to 1.442, P=0.431) or the secondary outcomes (P>0.05) between the two groups. Conclusion     The anesthesia regimen (volatile or intravenous anesthetics) has no association with the risk of occurrence of postoperative infection in adult  patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Analysis of Q-markers of Arisaema Cum Bile Acting on Stroke Based on UPLC-QTOF-MS/MS and TCMIP v2.0 / 中国实验方剂学杂志

ObjectiveTo predict the possible quality markers （Q-markers） of Arisaema Cum Bile in the prevention and treatment of stroke based on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spetrometry （UPLC-QTOF-MS/MS） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0. MethodUPLC-QTOF-MS/MS was employed with the mobile phase of 0.1% formic acid aqueous solution （A）-0.1% formic acid acetonitrile solution （B） for gradient elution （0-3 min， 0.2%-5%B； 3-5 min， 5%-8%B； 5-8 min， 8%-10%B； 8-14 min， 10%-25%B； 14-18 min， 25%-50%B； 18-20 min， 50%-70%B； 20-21 min， 70%-98%B； 21-23 min， 98%B； 23-24 min， 98%-0.2%B； 24-26 min， 0.2%B）， the flow rate of 0.5 mL·min-1 and electrospray ionization （ESI）. High quality MS/MS data were scanned in positive and negative ion modes with scanning range of m/z 50-1 500. A local database of the chemical constituents in Arisaema Cum Bile was established by UNIFI 1.8. Then the chemical constituents in Arisaema Cum Bile were characterized by matching with the local database and comparing with the reference substances and literature information. TCMIP v2.0 was used to obtain the targets corresponding to the identified components of Arisaema Cum Bile and stroke， and the "disease-formula" correlation analysis was carried out to screen the core targets by topological eigenvalues. DAVID 6.8 was used for enrichment analysis of Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway of core targets. According to the "five principles" of Q-markers and combined with literature reports， the Q-markers of Arisaema Cum Bile in the prevention and treatment of stroke were predicted， and the core components acting on these target genes were obtained. Cytoscape 3.8.0 was employed to draw the network diagram of "medicinal materials-active ingredients-target genes-pathways". Finally， AutoDock Vina 1.2.2 was used to calculate and verify the molecular docking between the candidate components and the key targets. ResultA total of 76 chemical components was identified in positive and negative ion modes， 85 core targets were collected for Arisaema Cum Bile in the prevention and treatment of stroke. A total of 31 stroke-related pathways， 23 target genes and 9 main active components of Arisaema Cum Bile acting on these genes were screened， and then we determined 4 possible Q-markers for Arisaema Cum Bile in the prevention and treatment of stroke according to the "five principles". ConclusionThe possible Q-markers of Arisaema Cum Bile for stroke are gallic acid， apigenin-6，8-di-C-glucoside， apigenin and cholic acid， and the target of these four components may be estrogen receptor alpha （ESR1）.

Application of Three Blood Stasis Models in Zebrafish in Evaluation of Anti-thrombosis and Anti-myocardial Hypoxia Activities of Notoginseng Radix et Rhizoma / 中国实验方剂学杂志

ObjectiveTo establish blood stasis models in zebrafish using three inducers and select the optimal model for evaluating the activity of Notoginseng Radix et Rhizoma in promoting blood circulation. MethodArachidonic acid （AA）， ponatinib， and isoprenaline （ISO） were used to induce blood stasis models in zebrafish. A normal group， a model group， a positive drug group， and Notoginseng Radix et Rhizoma water extract freeze-dried powder groups at different concentrations were set up. The staining intensity of cardiac erythrocytes and the fluorescence intensity of cardiac apoptotic cells were calculated， the anti-thrombotic effect and anti-myocardial hypoxia activity of Notoginseng Radix et Rhizoma were evaluated. The activities of water extract and 70% methanol extract of Notoginseng Radix et Rhizoma were compared based on the preferred AA- and ISO-induced blood stasis models in zebrafish and the difference in the chemical composition was analyzed by UHPLC LTQ-Orbitrap MS/MS. ResultAfter induction by AA and ponatinib， the staining intensity of cardiac erythrocytes was reduced （P<0.01）， and the fluorescence intensity of cardiac apoptotic cells increased after the induction by ISO （P<0.01）. The freeze-dried powder of the water extract of Notoginseng Radix et Rhizoma could antagonize the thrombosis in the AA-induced model （P<0.01） and the myocardial apoptosis in the ISO-induced model （P<0.05）， while no significant improvement in the thrombosis was observed in the ponatinib-induced model. The freeze-dried powder of 70% methanol extract of Notoginseng Radix et Rhizoma could inhibit myocardial apoptosis in the ISO-induced blood stasis model （P<0.01）， and the effect was stronger than that of the freeze-dried powder of Notoginseng Radix et Rhizoma water extract. The difference in chemical composition lay in some saponins （such as ginsenoside Re）， amino acids， and acetylenic alcohols. ConclusionAA， ponatinib， and ISO all can serve as inducers for the blood stasis model in zebrafish. AA- and ISO-induced models can be used to evaluate the activity of freeze-dried powder of Notoginseng Radix et Rhizoma water extract in promoting blood circulation. The chemical compositions of the freeze-dried powders of Notoginseng Radix et Rhizoma extracted with water and 70% methanol are quite different. For the ISO-induced blood stasis model， the freeze-dried powder of Notoginseng Radix et Rhizoma extracted with 70% methanol has a stronger ability against myocardial hypoxia. Saponins and acetylenic alcohols may be closely related to the effects of promoting blood circulation and resolving blood stasis.

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.