Mesenchymal stem cells have emerged as a promising cell therapy for anti-tumor research due to their homing properties,low immunogenicity,anti-angiogenic activity,anti-inflammatory properties,and paracrine effects.Paclitaxel has been clinically used for over thirty years in the treatment of various tumors such as ovarian cancer,lung cancer,and breast cancer.However,the broad-spectrum anti-tumor properties of paclitaxel are not possessed by the aforementioned cell therapies.Moreover,its adverse reactions,including peripheral neuropathy,bone marrow suppression,and gastrointestinal reactions,have long plagued cancer patients.In recent years,many studies have focused on combining cell therapy with chemotherapy to achieve better treatment outcomes,giving rise to a new drug delivery system that utilizes mesenchymal stem cells as carriers for delivering chemotherapeutic drugs.This review summarizes the research progress in MSC-based drug delivery systems for paclitaxel.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

Humans ; Bicuspid ; Dental Pulp Cavity ; Root Canal Therapy ; Tooth Root ; Mandible

In order to effectively solve the over-processing problem of Platycladi Cacumen Carbonisata, which was commonly used as a hemostatic drug in clinical application, we used the quantitative analysis method of multi-components by single marker(QAMS) in this study, with quercetin as internal reference to simultaneously determine the content of six flavonoids which can be used to control the internal quality of Platycladi Cacumen Carbonisata. Based on the comparison of QAMS and external standard method(ESM) results, the limit standards of contents were established as follows: isoquercitroside ≥0.002 0%, quercitroside ≥0.050%, quercetin ≥0.030%, kaempferol and amentoflavone both ≥0.010%, hinokiflavone ≥0.050%. Based on the color detection of Platycladi Cacumen and Platycladi Cacumen Carbonisata with different processing degrees, the law of influence of different processing degrees on the color of Platycladi Cacumen Carbonisata was found. A new external quality standard of Platycladi Cacumen Carbonisata was established by fitting curve of color recognition for the external quality control, based on which the standard ranges of ΔL~*, Δb~* and ΔE were-50.00--44.00, 6.00-11.00 and 45.00-50.00 respectively. Effective combination of established internal and external quality control standards by this study can be used to evaluate the processing degree and quality of Platycladi Cacumen Carbonisata more comprehensively and objectively, which can guarantee its clinical efficacy. At the same time, this study also provides reference and basis for further improving the quality control standard of Platycladi Cacumen Carbonisata.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Flavonoids ; Hemostatics ; Quality Control

To build up an identification method on cardiac glycosides in Taxillus chinensis and its Nerium indicum host, and evaluate the influence on medicine quality from host to T. chinensis, ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass-mass spectrometry(UPLC-Q-TOF-MS/MS)was applied. The samples of T. chinensis(harvested from N. indicum)and its N. indicum host were collected in field. The samples of T. chinensis(harvested from Morus alba)and its M. alba host was taken as control substance. All samples were extracted by ultrasonic extraction in 70% ethanol. Chromatographic separation was performed on an ACQUITY UPLC HSS T3 C_(18)(2.1 mm×100 mm,1.8 μm)column at 40 ℃. Gradient elution was applied, and the mobile phase was consisted of 0.1% formic acid water and acetonitrile. The 0.5 μL of sample solution was injected and the flow rate of the mobile phase was kept at 0.6 mL·min~(-1) in each run. It was done to identify cardiac glycosides and explore the chemical composition correlation in T. chinensis and its N. indicum host by analyzing positive and negative ion mode mass spectrometry data, elemental composition, cardiac glycoside reference substance and searching related literatures. A total of 29 cardiac glycosides were identified, 28 of it belonged to N. indicum host, 5 belonged to T. chinensis(harvested from N. indicum host), none of cardiac glycoside was identified in T. chinensis(harvested from M. alba host). The result could provide a reference in evaluating the influence in T. chinensis medicine quality from host. It was rapid, accurate, and comprehensive to identify cardiac glycosides in T. chinensis and its N. indicum host by UPLC-Q-TOF-MS/MS.
Cardiac Glycosides ; analysis ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Loranthaceae ; chemistry ; Nerium ; chemistry ; Phytochemicals ; analysis ; Tandem Mass Spectrometry

Objective: To establish a method for identifying cardiac glycosides in Scurrula parasitica and its Nerium indicum host by UPLC-Q-TOF-MS/MS. With safflower parasitoids with sweet-scented osmanthus trees as the host and their host osmanthus tree samples used for control, the chemical constituents of the cardiac glycosides were identified by comparison between the cardiac glycoside reference substances and literatures, so as to analyze the correlation between the safflower parasitoid and its host oleander glycoside components,and evaluate the host' s impact on the quality of Taxilli Herba. Method: Samples of S. parasitica (parasitic on N. indicum and Osmanthus fragrans),N. indicum and O. fragrans were collected. Samples of S. parasitica and its O. fragrans host were taken for control. All of the samples were extracted through ultrasonic extraction with 70%ethanol. ACQUITY UPLC HSS T3 C₁₈(2.1 mm×100 mm,1.8 μm) column was adopted with mobile phase A comprising 0.1%formic acid water and mobile phase B comprising acetonitrile for gradient elution. The sample size was 0.5 μL. The flow rate was 0.6 mL·min^-1. The column temperature was maintained at 40℃. MassLynx V4.1 software was used to analyze the data. Identification and correlation of chemical constitute of cardiac glycosides in S. parasitica and its N. indicum host were performed through analysis on cardiac glycosides reference substances,relevant literatures,elemental composition of compounds and positive and negative ion mode mass spectrometry data. Result: A total of 26 compounds of cardiac glycoside were identified,including 25 compounds of cardiac glycoside from N. indicum host,and 5 compounds of cardiac glycoside from S. parasitic(parasitic on N. indicum). none of cardiac glycosides were found in S. parasitica (parasitic on O. fragrans ) and its O. fragrans host. Conclusion: It was rapid,accurate and comprehensive to identify cardiac glycosides in S. parasitica (parasitic on N. indicum) and its N. indicum host by UPLC-Q-TOF-MS/MS. S. parasitica itself does not contain cardiac glycosides,its host may impact the quality of S. parasitica by delivering cardiac glycosides, a kind of its characteristic compound.

OBJECTIVE: To study the association between superior mesenteric artery hemodynamic indexes and scores of lower gastrointestinal symptoms rating scales(LGSRS) in patients with type 2 diabetic mellitus. METHODS: Totally 142 inpatients with type 2 diabetes with average age of 58.76±12.32 yrs were enrolled, who were treated from August 2016 to March 2018. The history, gender, age,course and BMI were recorded, and fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), 2-hour postprandial blood glucose(PBG), total cholesterol(TC), triglyceride(TG), urine ACR and LGSRS were determined. Ultrasonic scanning of mesenteric artery was performed for hemodynamic indexes, including artery inner diameter(ID), peak systolic velocity(PSV), end-diastolic velocity(EDV), and resistance index(RI)at starting part,first level branch, and second level branch from root of the superior mesenteric artery(SMA).Patients were divided into 2 groups according to their LGSRS, 74 patients with LGSRS≥6 were in positive group, and 68 patients with LGSRS<6 were in control group. RESULTS: 1. There were no significant differences between the 2 groups in gender, BMI, HbA1C, FBG, PBG,TC or TG(P>0.05), but the age and DD were significantly higher in positive group than in control group(P<0.05). 2. There were three patients(4.41%) who had atheroma or plaques in SMA in control group, while five patients in positive group(6.76%)(P>0.05). 3. There were no significant difference between positive group and control group in ID at starting part and first level branch of SMA, while ID at second level branch was significantly increased in positive group compared with control group [(3.83±0.85)mm vs.(3.53±0.90)mm, P<0.05)].4. RI at first(0.816±0.059 vs 0.842±0.063,P<0.05) and second level branch(0.813±0.076 vs 0.845±0.073, P<0.05) and PSV at first level branch[(110.89±46.89)cm/s vs(95.72±36.59)cm/s,P<0.05] were significantly high in positive group; there were no difference in other hemodynamic indexes between the groups. 5.Adjusted by age,DD,glycemic and lipidemic profile,Logistic regression showed that ID at first(RR=2.092,95%CI 1.080-4.050,P=0.029) and second level branch(RR=0.491,95%CI 0.252-0.955,P=0.36) and EDV at second level branch(RR=0.897,95%CI 0.824-0.976,P=0.012) were independent factors influencing LGSRS(P<0.05). CONCLUSION: Ultrosonic hemodynamic abnormalities in the superior mesenteric artery might be important factor in development of lower gastrointestinal tract symptoms in patients with type 2 diabetes.

AIM To observe the effects of Taxilli Herba from six different hosts (Morus alba L.,Salix babylonica L.,Camellia oleifera Abel.,Castanea mollissima B1.,Liquidambar formosana Hance and Nerium indicum Mill.) on lowering blood pressure of spontaneously hypertensive rats (SHR).METHODS SHR were randomly divided into 14 groups,captopril positive group (20 mg/kg),model group,and Taxilli Herba groups of 6 different hosts,and each Taxilli Herba group was further divided into high-dose group (5.9 g/kg) and low-dose group (1.48 g/kg);WKY,in addition,was the blank control.And the 20-day consective correspondence medication was applied to the groups,each with eight rats.The caudal arterial systolic blood pressure (SBP) was measured by tail-cuff method before the administration,and on the 10th day and 20th day of the administration.Anaesthesia was performed at the blood collection 12 h after the last administration;and thus final serum contents of nitric oxide (NO) and changes of superoxide dismutase (SOD) activity,plasmatic contents of angiotensin Ⅱ (Ang Ⅱ) and endothelin-1 (ET-1) were determined.RESULTS From the data before and after administration,an SBP drop among all SHR groups was observed on the 10th day of administration,among which the blood pressure lowering effect by high-dose Taxilli Herba from Morus alba L.was very obvious (P ＜ 0.01);remarkable SBP decrease on the 20th day of administration induced by Taxilli Herba from Salix babylonica L,Liquidambarformosana Hance and Camellia oleifera Abel,and high-dose Taxilli Herba from Morus alba L,low-dose Taxilli Herba from Castanea mollissima B1 were detected (P ＜ 0.01).No significant SBP variation was available between the model group and Taxilli Herba groups after10-day administration;all the Taxilli Herba groups exhibited obvious effect in lowering SBP except Taxilli Herba from Nerium indicum Mill,low-dose Taxilli Herba from Morus alba L.and high-dose Taxilli Herba from Castanea mollissimaBl.after 20-day administration,compared to the model group (P ＜ 0.05).Highdose Taxilli Herba from Morus alba L.and Salix babylonica L significantly decreased plasmatic Ang Ⅱ and ET-1 contents of SHR groups in comparison with the model group (P ＜0.01).High-dose Taxilli Herba from Morus alba L.,Salix babylonica L.and Liquidambarformosana Hance significantly increased serum NO release and superoxide dismutase (SOD) activity (P ＜ 0.01).CONCLUSION Taxilli Herba from the five different hosts,except Nerium indicum Mill,can lower blood pressure,and there exists an effect difference due to the host variation.

Objective To study the content difference of avicularin,quercitrin and quercetin in Herba Taxilli from different host plants. Methods The contents of avicularin,quercitrin and quercetin in Herba Taxilli were determined by RP-HPLC and the samples were prepared by ultrasonic extraction with methanol. The analytical column was UltImate XB-C18(250 mm×4.6 mm,5μm), the mobile phase was acetonitrile-methanol-0.1%phosphate with gradient elution,at a flow rate of 1.0 ml/min. The column tempera-ture was set at 25℃,the detection wavelength was 254 nm for avicularin and quercitrin,and 365 nm for quercetin. Results The lin-ear range of the above three ingrediets were 0.0992-1.9840(r=0.9999),0.2254-4.4580(r=0.9999)and 0.1258-2.5160μg(r=0.9997) and the average recovery rates(n=5)were 98.39%,97.08%and 98.159%,respectively. Their contents from different host plants were 0.0000-0.0398,0.3977-0.7639 and 0.0068-0.0231 mg/g in branches and 0.0167-0.1704,1.8626-11.0041,and 0.0185-0.1841 mg/g in leaves. Conclusion The method is accurate,simple and reproducible,and can be used for the quality control of Herba Taxilli.

BACKGROUNDPyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear.

METHODSC57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.

RESULTSThe expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS.

CONCLUSIONSThis study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.

Acute Lung Injury ; chemically induced ; prevention & control ; Amino Acid Chloromethyl Ketones ; pharmacology ; Animals ; Lipopolysaccharides ; toxicity ; Macrophages, Alveolar ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides ; pharmacology ; Pyroptosis ; drug effects