ABSTRACT
As a kind of immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are an important component of the immune microenvironment. MDSCs play a significant role in promoting tumor immune escape. In addition, non-immunological functions such as promoting angiogenesis can also promote tumor development with the deepening of research. MDSCs can promote tumor angiogenesis directly through vascular endothelial growth factor signaling pathway, or promote tumor growth and angiogenesis by secreting cytokines such as matrix metalloprotein-9, basic fibroblast growth factor, angiogenic peptide Bv8, platelet derived growth factor, exosomes, or interacting with other cells. Exploring the expansion, activation, recruitment and angiogenesis mechanism of MDSCs will provide new ideas for regulating the individualized diagnosis and treatment based on targeted MDSCs.
ABSTRACT
Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances.Here,we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry(UPLC-MS/MS).This enabled simultaneous quantification of 1136 acyl-carnitines(C0-C26)within 10-min with good sensitivity(limit of detection＜0.7 fmol),linearity(cor-relation coefficient＞0.992),accuracy(relative error＜20％),precision(coefficient of variation(CV),CV＜15％),stability(CV＜15％),and inter-technician consistency(CV＜20％,n=6).We also established a quantitative structure-retention relationship(goodness of fit＞0.998)for predicting retention time(tR)of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters(tR,ion-pairs,and collision energy).Furthermore,we quantified 514 acylcarnitines in human plasma and urine,mouse kidney,liver,heart,lung,and muscle.This provides a rapid method for quantifying acyl-carnitines in multiple biological matrices.
ABSTRACT
Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.
ABSTRACT
MET exon14 (METex14) skipping mutation is an independent driver gene in non-small cell lung cancer (NSCLC) . About 3%-4% of NSCLC patients carry METex14 skipping mutation. These patients have poor prognoses and poor responses to traditional chemotherapy and immunotherapy. Highly selective MET inhibitors such as capmatinib, tepotinib, savolitinib have shown good efficacy and safety data in clinical trials, which bring new treatment options for patients with METex14 skipping mutations.
ABSTRACT
Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR1, Rg1, and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
Subject(s)
Ginsenosides , Saponins , Chemometrics , Panax notoginseng , Cardiovascular Diseases , Chromatography, Liquid , Tandem Mass SpectrometryABSTRACT
Antibody-drug conjugates (ADCs) have overcome the limitations of traditional chemotherapy and targeted therapy with unique advantage of antibody targeting, and made breakthrough achievements in the treatment of lung cancer. At present, the researches of ADCs in non-small cell lung cancer mainly involve HER2, HER3, TROP2, MET, CEACAM5. Many ADCs have passed rigorous clinical trials, and have shown good safety and efficacy, which provides theoretical basis for individualized treatment of lung cancer.
ABSTRACT
ObjectiveAn analytical method was developed for the qualitative screening of 52 illegally adulterated weight-losing compounds in foods by ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. MethodsThe samples were extracted by methanol. Waters CORTECS T3 column （100 mm×2.1 mm， 2.7 μm） was used with acetonitrile -0.1% formic acid aqueous solution as mobile phases by gradient elution. The compounds were detected by electrospray ionization mass spectrometry and Q-TOF-MS detector in positive and negative ion mode. A standard spectrum library was established by reference standards， and the qualitative analysis was finished by the comparison of the retention time， parent ion and fragment ion accurate molecular mass of each compound in the sample and the library. ResultsThe method was specific without interference of blank matrix， and repeatable in sextuplicate. The detection limits of 52 compounds in 5 matrix were 1‒100 mg‧kg-1. The method was successfully applied to the analysis of actual samples，and 16 compounds were checked out in 246 samples. ConclusionThe method is accurate， specific and sensitive， which can be used to combat the illegal adulteration behavior effectively.
ABSTRACT
Objective To investigate the inhibitory effect of Xiaoaiping injection (XAP) combined with paclitaxel (PTX) on human ovarian cancer SK-OV-3 cells .Methods In vitro anti-proliferation activity study of XAP combined with PTX on hu-man ovarian cancer SK-OV-3 cells was performed using optical microscope and MTT assay .Human ovarian cancer SK-OV-3 cells were treated with PTX ,XAP ,PTX combined XAP or vehicle control .Each group of cells was treated with drugs for 24 h or 48 h .SK-OV-3 cell morphology was observed with optical microscope .MTT assay was used to detect the A value and cell vi-ability was calculated .In vivo effect of XAP combined with PTX on the growth of SK-OV-3 cells was determined in nude mice . In our study ,thirty-six mice were randomly divided into six groups :G1 (NS) ,G2 (PTX ,10 mg/kg) ,G3 (XAP ,20 ml/kg) , G4 (XAP ,50 ml/kg) ,G5 (PTX 10 mg/kg+XAP 20 ml/kg) and G6 (PTX 10 mg/kg+XAP 50 ml/kg) .Animals were trea-ted for 18 days .Body weight ,tumor volume and tumor inhibition rate were recorded and calculated .The results were analyzed by the SPSS 19 .0 software .Results In vitro study showed that SK-OV-3 cell viability decreased significantly in PTX com-bined XAP group compared to PTX group or XAP group ,in a time and dose-dependent manner .In vivo study showed that the combination of PTX and XAP resulted in decreased tumor weight significantly compared to the control or the PTX alone . Conclusion The combination of XAP and paclitaxel exhibited a synergistic effect both in vitro and in vivo in nude mouse tumor xenograft model .
ABSTRACT
Objective To evaluate the efficacy of dual stent placements for the treatment of occlusion/stenosis of subclavian artery associated with stenosis of adjacent vertebral artery initial site. Methods The clinical data of 9 patients with occlusion/stenosis of subclavian artery associated with stenosis of adjacent vertebral artery initial site were retrospectively analyzed. Stent implantations in the affected subclavian artery and vertebral artery were separately performed; the patients were followed up for 3-12 months after the treatment. The therapeutic efficacy was evaluated with the clinical symptoms and Doppler ultrasonic examination. Results Successful implantation of two stents was accomplished in all 9 patients, with the technical success rate of 100%. After the treatment, the blood flow in both the subclavian and vertebral arteries was unobstructed. Following-up examination showed that the subjective symptoms were obviously improved in all 9 patients, and no serious procedure-related complications occurred. Doppler ultrasound examination showed that no in-stent restenosis or stent displacement was observed. Conclusion For the treatment of occlusion/stenosis of subclavian artery associated with stenosis of adjacent vertebral artery initial site, dual stent placement technique is a safe and feasible means with satisfactory effect in improving vertebro-basilar arterial insufficiency.
ABSTRACT
Objective To evaluate whether the size,number or location of fibroids affect therapeutic efficacy of uterine artery embolization (UAE).Methods 84 patients with symptomatic uterine fibroids who had received uterine fibroid embolization with the use of polyvinyl alcohol(PVA)or gelfoam sponge particles(GSP).According to the lesion's size,number or location,all patients were divided into different groups and following -up as outpatients. Patient's symptomatic improvement and imaging following -up was assessed after UAE.Results A technically suc-cessful embolization was done in all patients.Postoperative 12 -month following -up was performed in 77 cases.No major life -threatening complications were found and the clinical symptoms were improved after UAE.In the different groups,the uterine size and the leiomyoma size after UAE were markedly decreased(t =5.842,P <0.05).Further comparison showed that the mean reduction in fibroids volume after UAE was not significant between the two groups, so was the mean reduction in uterine volume.Solitary leiomyoma group showed no significant difference in volume reduction rate of fibroids and uterine after UAE as compared with multiple leiomyoma group.Changes were not signifi-cantly in Submucosal uterine fibroids,Subserosal uterine fibroids,Intramural uterine fibroids.Conclusion UAE is an effective treatment for uterine fibroids.In this study,the size,number,and location of fibroids did not affect therapeutic efficacy or the complication rate of UAE.
ABSTRACT
Objective To explore the imaging features of external iliac artery-related postpartum hemorrhage, and to discuss its interventional therapy measures. Methods The clinical data and imaging findings of one patient with external iliac artery-related postpartum hemorrhage was retrospectively analyzed. The patient received interventional therapy at the intervention department of Shanxi provincial people ’s hospital. The relevant academic papers published in medical literature were reviewed. The common features of this condition were summarized, and the imaging features and the interventional therapy measures were discussed. Results A total of 4 patients, including authors’ case, with external iliac artery- related postpartum hemorrhage were reported in China. Of the 4 case , right external iliac artery-related postpartum hemorrhage was seen in 2 and bilateral external iliac artery-related postpartum hemorrhage was seen in other two. Embolization therapy of three abnormal branches of deep circumflex iliac artery that participated in the uterine blood supply was carried out. Immediately after the embolization the bleeding stopped. Conclusion For the treatment of postpartum hemorrhage, uterine arterial embolization should be followed by abdominal aorta angiography so as to check the external iliac artery. When recurrent bleeding occurs after uterine arterial embolization, the possibility that the abnormal branches of external iliac artery participates in the uterine blood supply should be considered. In performing the embolization of abnormal branches of external iliac artery, the catheter should be inserted to the distal end of the target vessel. Under DSA monitoring the embolic agent should be slowly injected into the targeted artery and the patient should be kept under close observation for blood reflux. Usually, the embolization of abnormal branches of external iliac artery will not cause ischemic symptoms of the pelvis and distal limbs.
ABSTRACT
OBJECTIVE:To study the stability of amoxicillin sodium and clavulanate potassium for injection in sodium chloride injection solution so as to offer a scientific basis for rational use of drug in clinical practice.METHODS:The external appearance and pH values of the mixed solution were observed,and the contents of Amoxicillin sodium and Clavulanate potas?sium were determined by HPLC method at5℃,25℃and37℃within3hours.RESULTS:The stability was related to the temperature and sunlight.CONCLUSION:The mixed solution is instable and should not be put in storage for long time.
ABSTRACT
Objective To evaluate the clinical value of the preoperative intra-arterial embolization of the nasopharyngeal angiofibromas. Methods The treatment group of 7 male patients with the nasopharyngeal angiofibromas were undergone angiographic evaluation and embolization of tumor-feeding vessels before surgery. All patients were embolized with gelfoam particles and PVA. The control group of 7 patients received surgical treatment without preoperative embolization. We compared the volumes of intraoperative bleeding and the blood transfusions during oprations between the two groups. Results All patients achieved symptomatic remission,with no complications. Comparing with the control group,the amount of intraoperative bleeding and the blood transfusions during operations were much less in the treatment group submitted to endovascular embolirzation.Marked edema in the peripheral region of tumor of the treatment group made the tumor easy to be dissociated. Conclusion The intraoperative bleeding can be reduced significantly by preoperative embolization of supplying arteries to the nasopharyngeal angiofibromas,therefore it should be used routinely as an adjunct to surgery. (J Intervent Radiol,2006,15: 345-347)