To observe the intervention effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration (RAS-RH) on the NOD-like receptor thermal protein domain associated protein 3/cysteinyl aspartate specific proteinase-1/gasdermin D (NLRP3/Caspase-1/GSDMD) signaling pathway and radiation-induced heart disease (RIHD).

A model was constructed using a single whole-body X-ray irradiation at a dose of 8 Gy. SPF-grade male Wistar rats were randomly divided into the normal group, the model group (X-ray 8 Gy), the experimental-L group (X-ray 8 Gy+25 mg·kg^-1·d^-1 RAS-RH by gavage) and the experimental-H group (X-ray 8 Gy+50 mg·kg^-1·d^-1 RAS-RH by gavage), with ten rats in each group. 2 h after the last administration, cardiac function was evaluated using echocardiography; serum levels of inflammatory factors, including interleukin-18 (IL-18), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent; relative protein expression levels of NLRP3, Caspase-1, GSDMD, IL-18 and IL-1β in myocardial tissue were detected using Western blotting.

The left ventricular ejection fraction (LVEF) in experimental-L group, experimental-H group, normal group and model group were (66.61±1.04)%, (71.89±0.69)%, (81.45±1.34)% and (47.62±1.67)%; the serum levels of IL-18 were (171.21±3.92), (145.60±3.37), (125.51±2.94) and (201.80±4.05) ng·mL^-1; the IL-1β levels were (43.03±0.68), (41.12±1.01), (36.12±0.98) and (51.19±0.85) ng·mL^-1; the TNF-α levels were (484.96±3.35), (441.24±3.94), (381.32±4.16) and (566.51±4.98) ng·mL^-1; the relative expression levels of NLRP3 protein in myocardial tissue were 0.54±0.02, 0.34±0.02, 0.20±0.02 and 0.75±0.03; the relative expression levels of Caspase-1 protein were 0.52±0.02, 0.44±0.02, 0.36±0.02 and 0.65±0.03; the relative expression levels of GSDMD-NT protein were 0.53±0.02, 0.42±0.01, 0.33±0.02 and 0.73±0.03; the relative expression levels of IL-18 protein were 0.50±0.02, 0.42±0.01, 0.13±0.01 and 0.63±0.02; the relative expression levels of IL-1β protein were 0.59±0.02, 0.42±0.02, 0.27±0.02 and 0.79±0.03, respectively. The indicators in the model group were significantly different compared to the normal group, and the indicators in the experimental-L and experimental-H groups were significantly different from the model group, with statistical significance (all P<0.05).

RAS-RH may improve RIHD by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.

To observe the clinical efficacy of medroxyprogesterone acetate and dinogestrel in the treatment of endometriosis (EMs) respectively.

EMs patients were divided into control group and treatment group according to cohort methods. Control group was given oral treatment with medroxyprogesterone acetate tablets, 10 mg each time, tid. Treatment group was given oral treatment with dinorgestrel tablets, 2 mg each time, qd. Patients in both groups continued to take the drug for 6 menstrual cycles. The levels of clinical efficacy, basal follicle-stimulating hormone (bF-SH), basal estradiol (bE₂), anral follicle count (AFC) and anti-mullerian hormone (AMH) before and after treatment were compared between the two groups.

In this trial, 38 cases were enrolled in the control group and 42 cases in the treatment group. After treatment, the total effective rates of the treatment group and the control group were 90.48% (38 cases / 42 cases) and 71.05% (27 cases / 38 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the levels of bF-SH in the treatment group and control group were (11.25±3.02) and (13.41±3.56) IU·L^-1, respectively; the bE₂ levels were (2.14±0.63) and (2.58±0.87) pmol·L^-1, respectively; the AFC levels were 7.80±1.69 and 6.97±1.63, respectively; the AMH levels were (1.12±0.14) and (1.03±0.21) ng·mL^-1, respectively; the above indexes were statistically significant (P<0.01,P<0.001). The adverse drug reactions of the treatment group mainly included abnormal vaginal bleeding, hot flashes and increased body weight, while the adverse drug reactions of the control group mainly included bleeding and hot flashes. The incidence of total adverse drug reactions in the treatment group and the control group was 11.90% (5 cases/42 cases) and 7.89% (3 cases/38 cases), respectively, and the difference was not statistically significant (P>0.05).

Dienogest tablets has a good effect in the treatment of EMs patients, which can effectively relieve pain symptoms, inhibit estrogen expression, improve uterine artery blood flow, and reduce the level of inflammation in the body, with low adverse drug reactions.

To investigate the effects and mechanism of Polygonum orientale flower (POR) extract on exercise arrhythmia (EA) in rats after exhaustive exercise.

The EA rat model was induced by 8 weeks of exhaustive weight-bearing swimming exercise and was randomly divided into model group and experimental -L, -M, -H groups, with 12 rats per group. Twelve normal rats were selected as the normal group. On the modeling day, normal and model groups were given pure water by intragastric administration. Experimental -L, -M, -H groups were given 50, 100 and 200 mg·kg^-1 POR extract solution by intragastric administration, respectively. Five groups were administrated with once a day for 8 weeks. The latent time and duration of arrhythmia in rats were detected by electrocardiograph. The contents of adenosine triphosphate (ATP), the activities of Na⁺/K⁺ATP and the contents of superoxide dismutase (SOD) in myocardial tissue were measured by corresponding kit. The transcriptional levels of calmodulin (CaM) and calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) in rat myocardium were measured by real-time fluorescence quantitative polymerase chain reaction.

The latent time of arrhythmia in experimental -M, -H groups and model group were (9.77±1.48), (10.61±1.61) and (7.44±2.12) min; the duration were (33.25±6.39), (20.01±3.89) and (71.44±13.68) min. The ATP contents in experimental -M, -H groups, model group and normal group were (26.45±2.96), (29.44±1.89), (10.38±1.22) and (34.50±4.24) ng·g prot^-1; the Na⁺/K⁺ ATP activities were (17.27±0.92), (19.57±1.33), (5.14±0.80) and (20.00±2.11) U·g prot^-1; SOD contents were (89.22±9.07), (86.29±7.22), (73.62±7.36) and (89.43±8.85) U·mg prot^-1; the relative expression levels of CaM mRNA in myocardial tissue were 1.28±0.08, 1.06±0.08, 2.34±0.30 and 1.00±0.10; the relative expression levels of CaMK Ⅱ mRNA in myocardial tissue were 1.46±0.09, 1.15±0.09, 2.80±0.19 and 1.00±0.11, respectively. Compared with model group, the differences of above indexes in experimental -M, -H groups were statistically significant (all P<0.05).

POR extract can effectively treat the rats with EA, and the mechanism is related to the increase of ATP contents, Na⁺/K⁺ ATP and antioxidant activities, and inhibition of Ca²⁺/CaM/CaMK Ⅱ signaling pathway.

To investigate the effect of ulinastatin on epithelial-mesenchymal transition (EMT) of bladder cancer T24 cells.

Bladder cancer T24 cells were randomly divided into blank, control, experimental, combined groups. The cells in the blank group were cultured normally; and the cells in the control group were treated with RPMI-1640 medium containing 0.75 μmol·L^-1 KYA1797K; the cells in the experimental group were treated with RPMI-1640 medium containing 5.00 μmol·L^-1 ulinastatin and the cells in the combined group were treated with RPMI-1640 medium containing 5.00 μmol·L^-1 ulinastatin and 0.75 μmol·L^-1 KYA1797K. The treatment time was 48 hours. The cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. Transwell assay was used to detect the invasion and migration ability of cells. The protein expression levels of epithelial-mesenchymal transition related proteins, wingless-type MMTV integration site family 3α (Wnt3α) and β-catenin were detected by Western blotting.

The survival rates of the blank group, control group, experimental group and combined group were (100.00±0.00)%, (73.28±6.37)%, (76.98±5.82)% and (40.36±3.21)%, respectively; the numbers of invasive cells were 66.83±8.18, 33.33±3.27, 38.67±4.32 and 11.33±1.21, respectively; the migration number were 79.33±6.38, 53.00±6.26, 52.33±3.14 and 28.33±5.28, respectively; the relative expression levels of E-cadherin protein were 0.23±0.08, 0.51±0.02, 0.58±0.05 and 0.82±0.03, respectively; the relative expression levels of Vimentin protein were 0.78±0.03, 0.55±0.02, 0.58±0.06 and 0.27±0.06, respectively; the relative expression levels of N-cadherin were 0.83±0.08, 0.59±0.02, 0.62±0.02 and 0.31±0.09, respectively; the relative expression levels of Wnt3α protein were 0.85±0.09, 0.28±0.13, 0.29±0.05 and 0.12±0.01, respectively; the relative expression levels of β-catenin were 0.81±0.05, 0.25±0.07, 0.22±0.03 and 0.08±0.02, respectively. The above indexes in the control group and experimental group were significantly different from those in the blank group and combined group (all P<0.05).

Ulinastatin can inhibit the epithelial-mesenchymal transition of bladder cancer T24 cells, and its mechanism may be related to the inhibition of Wnt signaling pathway.

To investigate the effects of microRNA-425-5p (miR-425-5p) targeting fibroblast growth factor 9 (FGF9) on the proliferation, glucose metabolism and olaparib resistance of ovarian cancer cells.

Human ovarian cancer cell line SKOV3 were divided into control group (normal culture), NC inhibitor group (transfected empty vector miR-NC), miR-425-5p inhibitor group (transfected miR-425-5p inhibitor), si-NC group (transfected si-NC on the basis of miR-425-5p inhibitor group), si-FGF9 group (transfected si-FGF9 on the basis of miR-425-5p inhibitor group). Quantitative real time polymerase chain reaction was used to detect the expression levels of miR-425-5p and FGF9 in cells. The cell proliferation rate was detected by 5-ethynyl-2′-deoxyuridine (EdU) assay. Lactic acid production and glucose absorption were measured by lactic acid metabolism and glucose detection kit. The survival rate of cells in each group was detected by cell counting kit-8 assay. Western blot was used to detect signal transducer and activator of transcription 3/sirtuin 3 (STAT3/SITR3) signaling pathway related protein expression levels in each group.

The proliferation rate were (84.11±14.76)%, (36.12±6.95)%, (34.32±6.62)% and (77.37±12.83)% in the NC inhibitor group, miR-425-5p inhibitor group, si-NC group and si-FGF9 group, respectively; the relative lactic acid production were 1.02±0.13, 0.71±0.09, 0.74±0.09 and 0.89±0.10, respectively; the relative glucose absorption values were 0.99±0.14, 0.68±0.08, 0.70±0.09 and 0.91±0.11, respectively; the survival rates under 40 μmol·L^-1 olaparib were (59.86±9.55)%, (41.08±7.72)%, (40.25±7.02)% and (55.71±7.68)%, respectively; the relative expression levels of STAT3 protein were 1.01±0.17, 0.68±0.10, 0.66±0.09 and 0.88±0.12, respectively; the relative expression levels of SITR3 protein were 0.98±0.17, 1.84±0.28,1.85±0.29 and 1.23±0.20, respectively. The above indexes of miR-425-5p inhibitor group were compared with those of NC inhibitor group, and those of si-FGF9 group were compared with those of si-NC inhibitor group, and the differences were statistically significant (P<0.01, P<0.001).

Silting miR-425-5p can inhibit the proliferation and glucose metabolism of ovarian cancer cells, and reduce the resistance of cells to olaparib, which may be achieved by up-regulating FGF9 level and inhibiting STAT3/SIRT3 signaling pathway.

To evaluate the efficacy and safety of Morinda officinalis oligoes (MOs) capsules in the 24-week maintenance phase treatment of mild and moderate depression.

This study was the maintenance phase part of phase Ⅳ clinical trial for MOs capsules. Patients who was diagnosed as mild or moderate depressive episode were included into this study. Participants who were finished MOs capsules’ 8-week acute phase and 24-week continuation phase would go on to take MOs capsules for 24 weeks. During the acute phase, patients would take the start treatment dosage MOs capsules 300 mg qd for 2 weeks. On the final of week two, if HAMD-17 reduce rate <30%, patients would take an increased dosage treatment about MOs capsules 600 mg qd, and if HAMD-17 reduce rate ≥30%, patients would continue the start treatment dosage. The dosage remained unchanged during the first 16 weeks in maintenance phase, and from week 17 to week 24 the dosage would be cut to the half. The changes from baseline to endpoint of Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Clinical Global Impression-Severity (CGI-S) and Arizona Sexual Experience Scale (ASEX) were evaluated, and recovery rate, relapse rate, relapse time were reported. The incidence of adverse events was reported.

The scores of HAMA at baseline and after treatment were (3.64±2.51) and (2.84±2.60) points, the difference was statistical significant (P<0.05). The scores of HAMD-17 at baseline and after treatment were (4.00±2.13) and (3.90±4.09) points, CGI-S were (1.02±0.51) and (0.90±0.79) points, scores of ASEX were (16.15±5.65) and (15.95±5.70) points, the differences were not statistical significant (P>0.05). After 24-week’s treatment, the recovery rate was 84.21% (96 cases/114 cases), the relapse rate was 6.14% (7 cases/114 cases), the relapse time was (82.14±39.66) d. The incidence of treatment-related adverse events was 33.05% (39 cases/118 cases).

MOs capsules can be used for the maintenance treatment of mild or moderate depression, and were well tolerated and safe.

To establish liquid chromatography-mass spectrometry (LC-MS/MS) quantitative method for determining the blood concentration of Upatinib in human plasma.

Upatinib 15N-d2 was used as the internal standard, and acetonitrile was used for protein precipitation pretreatment. Separate using a Waters BEH C₁₈ (2.4 mm×50.0 mm, 1.7 μm) chromatographic column; acetonitrile (containing 0.1% formic acid) and 0.1% formic acid aqueous solution were used as mobile phases, with gradient elution at a flow rate of 0.3 mL·min^-1 and column temperature of 40 ℃. The ion pair used for quantitative analysis was m/z 388.90→255.90 (Upatinib) and m/z 384.10→256.20 (Upatinib-15N-d2, internal standard) respectively by using an electrospray ion source and positive ion multi reaction monitoring mode scanning. The specificity, standard curve, quantitative cutoff, precision, recovery rate, dilution reliability, matrix effect and stability of the method were examined.

There is no mutual interference between endogenous components, internal standards and Upatinib in plasma. The linear relationship between the mass concentration of 0.75-60.00 ng·mL^-1 Upatinib and peak area is good (r=0.998 6), the standard curve equation was y=8.24×10^-2x+0.61×10^-2, with a lower limit of quantification of 0.75 ng·mL^-1. The intra-day and inter-day batch precision coefficients of variation of the quality control samples are both ≤5.3%. The accuracy of the sample concentration after 5-fold dilution is 1.1%, and the coefficient of variation is 4.6%. The matrix effect factors of low and high-quality plasma quality control samples are 1.1 and 1.0, respectively. The stability of whole blood samples and plasma samples meets the requirements of biological sample analysis.

The method used is simple, rapid, highly accurate, and sensitive, and is suitable for determining the concentration of Upatinib in human plasma. It can be used for pharmacokinetic and bioequivalence studies of Upatinib in healthy individuals.

To investigate the effect of circRNA_0044556 on the resistance of triple-negative breast cancer (TNBC) to paclitaxel (PTX) and the mechanism of drug resistance.

PTX resistant TNBC cells (MDA-MB-231/PTX) were obtained by exposing the human TNBC cell (MDA-MB-231) to increasing concentrations of PTX. MDA-MB-231 and MDA-MB-231/PTX cells in logarithmic growth phase were treated with circRNA_0044556 short hairpin RNA (sh-circRNA_0044556) and negative control (sh-NC), respectively. The groups were finally divided into MDA-MB-231-NC, MDA-MB-231-circRNA_0044556, MDA-MB-231/PTX-NC and MDA-MB-231/PTX-circRNA_0044556 groups. The expression level of circRNA_0044556 in cells was determined by real-time quantitative polymerase chain reaction (RT-qPCR); methyl thiazolyl tetrazolium assay and colony formation assay were used to observe cell proliferation; flow cytometry was used to observe cell apoptosisand; Western blot was used to observe the expression of cell proliferation and apoptosis-related proteins.

The relative expression levels of circRNA_0044556 in MDA-MB-231/PTX, MDA-MB-231 and MCF-10A cells were 6.08±0.59, 3.36±0.11 and 1.00±0.02, respectively, and the differences were statistically significant (all P<0.001). Proliferation rates of MDA-MB-231-NC and MDA-MB-231-circRNA_0044556 groups were (100.00±0.84)% and (54.38±1.20)%; the apoptosis rates were (2.41±0.34)% and (21.65±0.29)%, respectively, and the differences were statistically significant (all P<0.001). The proliferation rates of MDA-MB-231/PTX-NC and MDA-MB-231/PTX-circRNA_0044556 groups were (112.29±1.19)% and (61.33±1.24)%; the apoptosis rates were (2.08±0.07)% and (14.38±0.16)%, respectively, the differences were all statistically significant (all P<0.001). The relative protein expression level of Ki-67 in MDA-MB-231-NC and MDA-MB-231-circRNA_0044556 groups were 1.00±0.02 and 0.67±0.02; the relative protein expression of Bcl-2-associated X protein (Bax) were 1.00±0.02 and 1.46±0.03; and the differences were statistically significant (all P<0.05). The relative relative protein expression levels of Ki-67 in MDA-MB-231/PTX-NC group and MDA-MB-231/PTX-circRNA_0044556 group were 1.00±0.03 and 0.81±0.01, respectively; the relative expression levels of Bax protein were 1.00±0.02 and 1.55±0.02, respectively; the relative expression levels of Bcl-2 protein were 1.00±0.03 and 0.79±0.01, respectively. The above indexes in MDA-MB-231/PTX-NC group were significantly different from those in MDA-MB-231/PTX-circRNA_0044556 group (all P<0.05).

Knocking down the expression of circRNA_0044556 can inhibit the malignant progression and PTX resistance of TNBC cells.