Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.
Humans ; Oleanolic Acid ; Endothelial Cells ; Esters ; Cinnamates ; Triterpenes/chemistry* ; Molecular Structure

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

OBJECTIVE: To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats. METHODS: A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures. RESULTS: Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion. CONCLUSION The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Male ; Rats ; Animals ; Prostate/diagnostic imaging* ; Paraffin ; Indocyanine Green ; Rats, Sprague-Dawley ; Fluorescent Dyes

Objective: To explore the expression characteristics and role of Krüppel-like factor 4 (KLF4) in macrophage inflammatory response and its effects on inflammatory response and organ injury in septic mice, so as to lay a theoretical foundation for targeted treatment of burns and trauma sepsis. Methods: The method of experimental research was used. Mouse RAW264.7 macrophages and primary peritoneal macrophages (PMs) isolated from 10 male C57BL/6J mice aged 6-8 weeks were used for the experiments. RAW264.7 macrophages and PMs were treated with endotoxin/lipopolysaccharide (LPS) for 0 (without treatment), 1, 2, 4, 6, 8, 12, and 24 h, respectively, to establish macrophage inflammatory response model. The mRNA expression of interleukin 1β (IL-1β), IL-6, CC chemokine ligand 2 (CCL2) and tumor necrosis factor-α (TNF-α) were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR), and the LPS treatment time was determined for some of the subsequent experiments. RAW264.7 macrophages were treated with LPS for 0 and 8 h, the localization and protein expression of KLF4 were detected by immunofluorescence method, transcriptome sequencing of the cells was performed using the high-throughput sequencing technology platform, and the differently expressed genes (DEGs) between the two time points treated cells were screened by DESeq2 software. RAW264.7 macrophages and PMs were treated with LPS for 0, 1, 2, 4, 6, 8, 12, and 24 h, respectively, and the mRNA and protein expressions of KLF4 were detected by real-time fluorescence quantitative RT-PCR and Western blotting, respectively. RAW264.7 macrophages were divided into negative control (NC) group and KLF4-overexpression group according to the random number table, which were treated with LPS for 0 and 8 h respectively after transfection of corresponding plasmid. The mRNA expressions of KLF4, IL-1β, IL-6, CCL2, and TNF-α were detected by real-time fluorescence quantitative RT-PCR, while the protein expression of KLF4 was detected by Western blotting. The number of samples in aforementioned experiments was all 3. Forty male C57BL/6J mice aged 6-8 weeks were divided into KLF4-overexpression group and NC group (with 20 mice in each group) according to the random number table, and the sepsis model of cecal ligation perforation was established after the corresponding transfection injection was injected respectively. Twelve mice were selected from each of the two groups according to the random number table, and the survival status within 72 hours after modeling was observed. Eight hours after modeling, the remaining 8 mice in each of the two groups were selected, the eyeball blood samples were collected to detect the levels of IL-1β and IL-6 in serum by enzyme-linked immunosorbent assay, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum by dry chemical method. Subsequently, the heart, lung, and liver tissue was collected, and the injury was observed after hematoxylin-eosin staining. Data were statistically analyzed with independent sample t test, Cochran & Cox approximate t test, one-way analysis of variance, Dunnett test, Brown-Forsythe and Welch one-way analysis of variance, Dunnett T3 test, log-rank (Mantel-Cox) test. Results: Compared with that of LPS treatment for 0 h, the mRNA expressions of IL-1β in RAW264.7 macrophages treated with LPS for 6 h and 8 h, the mRNA expressions of IL-6 in RAW264.7 macrophages treated with LPS for 4-12 h, the mRNA expressions of CCL2 in RAW264.7 macrophages treated with LPS for 8 h and 12 h, and the mRNA expressions of TNF-α in RAW264.7 macrophages treated with LPS for 4-8 h were significantly up-regulated (P<0.05 or P<0.01), while the mRNA expressions of IL-1β and CCL2 in PMs treated with LPS for 4-8 h, the mRNA expressions of IL-6 in PMs treated with LPS for 2-24 h, and the mRNA expressions of TNF-α in PMs treated with LPS for 2-12 h were significantly up-regulated (P<0.05 or P<0.01). Eight hours was selected as the LPS treatment time for some of the subsequent experiments. KLF4 mainly located in the nucleus of RAW264.7 macrophages. Compared with those of LPS treatment for 0 h, the protein expression of KLF4 in RAW264.7 macrophages treated with LPS for 8 h was obviously decreased, and there were 1 470 statistically differentially expressed DEGs in RAW264.7 macrophages treated with LPS for 8 h, including KLF4 with significantly down-regulated transcriptional expression (false discovery rate<0.05, log₂ (fold change)=-2.47). Compared with those of LPS treatment for 0 h, the mRNA expressions of KLF4 in RAW264.7 macrophages treated with LPS for 6-24 h, the protein expressions of KLF4 in RAW264.7 macrophages and PMs treated with LPS for 1-24 h, and the mRNA expressions of KLF4 in PM treated with LPS for 4-24 h were significantly decreased (P<0.05 or P<0.01). Compared with those in NC group, the mRNA (with t' values of 17.03 and 8.61, respectively, P<0.05 or P<0.01) and protein expressions of KLF4 in RAW264.7 macrophages treated with LPS for 0 h and 8 h in KLF4-overexpression group were significantly increased, the mRNA expressions of IL-6 and CCL2 increased significantly in RAW264.7 macrophages treated with LPS for 0 h (with t values of 6.29 and 3.40, respectively, P<0.05 or P<0.01), while the mRNA expressions of IL-1β, IL-6, CCL2, and TNF-α decreased significantly in RAW264.7 macrophages treated with LPS for 8 h (with t values of 10.52, 9.60, 4.58, and 8.58, respectively, P<0.01). The survival proportion of mice within 72 h after modeling in KLF4-overexpression group was significantly higher than that in NC group (χ²=4.01, P<0.05). Eight hours after modeling, the serum levels of IL-1β, IL-6 and ALT, AST of mice in KLF4-overexpression group were (161±63), (476±161) pg/mL and (144±24), (264±93) U/L, respectively, which were significantly lower than (257±58), (654±129) pg/mL and (196±27), (407±84) U/L (with t values of 3.16, 2.44 and 4.04, 3.24, respectively, P<0.05 or P<0.01) in NC group. Eight hours after modeling, compared with those in NC group, the disorder of tissue structure of heart, lung, and liver, inflammatory exudation, and pathological changes of organ parenchyma cells in KLF4-overexpression group were obviously alleviated. Conclusions: The expression of KLF4 is significantly down-regulated in LPS-induced macrophage inflammatory response, which significantly inhibits the macrophage inflammatory response. KLF4 significantly enhances the survival rate of septic mice and alleviates inflammatory response and sepsis-related organ injury.
Male ; Mice ; Animals ; Mice, Inbred C57BL ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha ; Kruppel-Like Factor 4 ; Interleukin-6 ; Wound Infection ; Sepsis

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Breast Neoplasms/pathology* ; Drug Resistance ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Treatment Outcome

OBJECTIVE: To establish a method for the determination of formic acid in urine by automatic headspace-gas chromatography-mass spectrometry. METHODS: The urine sample was added with 3 mL 15.00%(V/V) sulfuric acid ethanol and heated in an automatic headspace sampler. The formic acid and ethanol underwent an esterification reaction to produce ethyl formate which was separated by gas chromatographic column and detected by mass spectrometer. The quantification was based on external standard method. RESULTS: The linear range of the method was 2.93-97.60 mg/L, with the regression equation correlation coefficient of 0.999 5. The detection limit was 0.65 mg/L and the minimum quantitative limit was 2.17 mg/L, with the recoveries of 95.61%-106.47%. The within-run relative standard deviation(RSD) ranged from 2.52% to 8.05% and the between-run RSD ranged from 6.58% to 8.42%. CONCLUSION: The method has simple pretreatment, good specificity, high precision and has little interference. It is suitable for large scale rapid determination of formic acid in urine in occupational contact population, patients with acute methanol poisoning and general population.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

BACKGROUND: Chemotherapy is the most important method for cancer treatment. However, chemotherapy induced nausea and vomiting (CINV) has a profound effect on patients. In recent years, there have been new antiemetic drugs, such as aprepitant. We review the curative effect of aprepitant with tropisetron and dexamethasone for prevention of nausea and vomiting in patients receiving Cisplatin chemotherapy. METHODS: Observation is divided into three stages. Whole study phase (0-120 h after chemotherapy administration), acute phases (0-24 h), and delayed phase (24 h-120 h). The primary endpoints were complete response (CR) and complete prevention (CP) during the three different study phase. RESULTS: In the whole study phase, 86.02% of patients achieved CR; in acute phases and delayed phases were 89.25%, 87.1%, respectively. CP were 46.22%, 83.87%, 45.16%, respectively. Anti-CINV effect was significantly associated with age distribution (P=0.008). CONCLUSIONS Aprepitant with tropisetron and dexamethasone prevented effectively CNIV for patients receiving Cisplatin chemotherapy. This combination could improve the quality of life and the compliance of patient with chemotherapy.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; Aprepitant ; Cisplatin ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Morpholines ; pharmacology ; Nausea ; chemically induced ; prevention & control ; Quality of Life ; Vomiting ; chemically induced ; prevention & control

The present study was designed to evaluate the cardioprotective effect of latifolin on pituitrin(Pit) or isoproterenol(ISO)-induced myocardial injury in rats, and further investigate its underlying mechanisms. Rats were administrated sublingually with pituitrin or subcutaneously with isoproterenol to induce acute myocardial ischemia in rats, and lead II electrocardiograph was recorded. In rats with isoproterenol, ELISA assay or colorimetric method was used to detect the content or activity of myocardial injury markers in serum, and the SOD activity and MDA content in myocardium were detected by colorimetric assay; histopathological examination was conducted by HE staining; the frozen section of myocardial tissues was used for DCFH-DA fluorescent staining to detect the content of ROS in myocardium; Western blot was used to detect the protein expression levels of Nrf2, Keap1, HO-1 and NQO1 in myocardium. Results showed that latifolin significantly inhibited ST-segment changes induced by pituitrin or isoproterenol, and increased heart rate. Further mechanism study showed that latifolin reduced cardiac troponin I(cTnI) level, aspartate transaminase(AST) and lactate dehydrogenase(LDH) activities in serum, increased myocardial superoxide dismutase(SOD) activity and reduced myocardial malondialdehyde(MDA) level, and protected myocardium with less necrosis, infiltration of inflammatory cells and fracture of myocardial fibers. Furthermore, latifolin obviously reduced ROS level in myocardium, inhibited the expression of Kelch-like ECH-associated protein-1(Keap1), increased the nuclear translocation of nuclear factor erythroid 2 related factor 2(Nrf2), and promoted the expression of Heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1) in myocardial tissues. Our data suggest that latifolin has a potent protective effect against pituitrin or isoproterenol-induced myocardial injury, which may be related to inhibition of oxidative stress by activating Nrf2 signaling pathway.