To observe the clinical efficacy and safety of escitalopram oxalate tablets combined with levodopa and benserazide hydrochloride tablets in the treatment of patients with Parkinson’s disease.

The patients with Parkinson’s disease were randomly divided into control group and treatment group. The control group received levodopa and benserazide hydrochloride tablets 125 mg per time, tid, orally. On the basis of control group, the treatment group received escitalopram oxalate tablets 10 mg per time, qd, orally. Two groups were treated for 3 months. The clinical efficacy, Montreal cognitive assessment (MoCA) scores, Hamilton depression rating scale (HAMD) scores, unified Parkinson’s disease rating scale (UPDRS) scores, the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and nerve growth factor (NGF), and safety were compared between two groups.

Treatment group was enrolled 116 cases, 4 cases dropped out, and 112 cases were finally included in the statistical analysis. Control group was enrolled 116 cases, 2 cases dropped out, and 114 cases were finally included in the statistical analysis. After treatment, the total effective rates of treatment and control group were 82.14% (92 cases / 112 cases) and 65.79% (75 cases / 114 cases), with significant difference (P<0.05). After treatment, the MoCA scores of treatment and control groups were (24.89±2.87) and (19.58±2.62) points, the HAMD scores were (10.45±1.06) and (15.84±1.49) points, the UPDRS scores were (40.06±5.28) and (47.78±5.52) points, the IL-6 levels were (4.12±0.63) and (6.71±1.13) mg·L^-1, the TNF-α levels were (8.71±1.64) and (11.14±2.05) mg·L^-1, the NGF levels were (41.56±5.20) and (30.47±4.14) ng·mL^-1, respectively. The differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of treatment group were somnolence and nausea/vomiting, while those in control group were nausea/vomiting and constipation. The total incidences of adverse drug reactions in treatment and control groups were 15.18% and 12.28%, without statistically significant difference (P>0.05).

Escitalopram oxalate tablets combined with levodopa and benserazide hydrochloride tablets significantly improves clinical efficacy in the treatment of patients with Parkinson’s disease, which can significantly ameliorate the inflammatory responses and neurotrophic factor levels, without increasing the incidence of adverse drug reactions.

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 analyze the effect of insulin degludec/insulin aspart injection combined with metformin extended-release tablets on insulin resistance in patients with type 2 diabetes mellitus (T2DM).

T2DM patients were divided into control group and treatment group using a cohort method. The control group received oral metformin extended-release tablets (0.5 g, tid) and subcutaneous injections of insulin glargine injection (10 U, qd), while the treatment group received oral metformin extended-release tablets (0.5 g, tid) and subcutaneous injections of insulin degludec/insulin aspart injection (0.1-0.2 U·kg^-1·d^-1, evenly divided before breakfast and dinner). Both groups were treated for 12 weeks. The efficacy, blood glucose control [fasting blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin A1c(HbA1c)], insulin function [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment-β (HOMA-β)]were compared, and safety was evaluated.

A total of 49 cases were enrolled in the treatment group and 51 cases in the control group. The overall effective rates in the treatment and control groups were 93.88% (46 cases/49 cases) and 80.39% (41 cases/51 cases), respectively, showing a statistically significant difference (P<0.05). After treatment, the fasting blood glucose levels in the treatment and control groups were (5.83±0.79) and (6.53±0.81) mmol·L^-1; the 2-hour postprandial blood glucose levels were (7.73±0.86) and (8.41±0.97) mmol·L^-1; HbA1c levels were (6.34±0.88)% and (6.80±0.92)%; FINS levels were (6.02±1.13) and (7.13±1.04) mU·L^-1; HOMA-IR values were 1.56±0.20 and 2.07±0.23; HOMA-β values were 51.67±3.18 and 47.06±3.31, respectively, with all differences being statistically significant (all P<0.05). The adverse drug reactions in the treatment group mainly included hypoglycemia, nausea, dizziness, and diarrhea, while the adverse drug reactions in the control group mainly included hypoglycemia and nausea. The incidence of adverse drug reactions was 10.20% (5 cases/49 cases) in the treatment group and 11.76% (6 cases /51 cases) in the control group, with no statistically significant difference (P<0.05).

The combination of insulin degludec/insulin aspart injection and metformin extended-release tablets can improve insulin resistance and regulate blood glucose levels in T2DM patients, with good safety profiles.

To compare the clinical efficacy and safety of sodium bicarbonate ringer’s injection and 0.9% NaCl as resuscitation fluid in the treatment of patients with diabetic ketoacidosis (DKA).

Patients with DKA were randomly divided into treatment group and control group. After enrollment, the treatment group was immediately given sodium bicarbonate ringer’s , and the control group was given 0.9% NaCl for fluid resuscitation. Other treatment protocols for DKA were the same in two groups. The incidence of hyperchloremia in 96 hour the change value of chloride in 96 hours (with the maximum value minus the baseline value), the total volume of fluid administered over 24 hours, the volume of urine produced over 24 hours, and the incidence of acute kidney injury(AKI) were compared between the two groups. Additionally, the incidence of hypokalemia in the two groups during the 96-hour observation period was recorded, and the safety of the intervention was evaluated.

The study cohort comprised 20 cases in the treatment group, of whom two were dislodged, finally 18 cases were included in the statistical analysis. In the control group, 20 cases were enrolled, with one case being dislodged, leaving 19 cases included in the statistical analysis. The incidence of 96 hour hyperchloraemia in the treatment group and the control group was 27.78% (5 cases/18 cases) and 73.68% (14 cases/19 cases), respectively. Furthermore, the change values of chloride in 96 hour were 11.05(9.30, 13.13) and 19.10(14.10, 29.10) mmol·L^-1, respectively. Notably, the differences between the two groups were statistically significant(all P<0.05). The total fluid volume was 3 410.00 and 3 600.00 mL, the 24 hour urine output was 2 075.00 and 2 950.00 mL, and the incidence of AKI was 0% (0 cases/18 cases) and 5.26% (1 cases/19 cases) in the treatment group and the control group, respectively. No statistically significant differences were observed in any of the statistical comparisons(all P>0.05). However, the incidence of hypokalaemia in the treatment group(22.22%) was lower than that in the control group(57.89%), and this difference was statistically significant (P<0.05).

The administration of sodium bicarbonate ringer’s injection for the resuscitation of patients with diabetic ketoacidosis has been demonstrated to reduce the incidence of hyperchloremia at 96 hours, and have good safety.

To investigate the effects of baicalein on apoptosis and immune escape of laryngeal carcinoma cells and its mechanism.

Human laryngeal carcinoma TU686 cells were randomly divided into control group(routine culture), baicalein group (50 μmol·L^-1 baicalein), Vector group (transfected with Vector+50 μmol·L^-1 baicalein) and CD47 group [transfected with differentiation cluster 47(CD47) +50 μmol·L^-1 baicalein]. Cell proliferation and apoptosis were detected by 5-acetylidene-2′-deoxyuridine (Edu) method and Annexin V-FITC/PI double staining method. The expression of proliferative and apoptotic proteins were detected by Western blot. Human peripheral lymphocytes were co-cultured with cells in each group to detect the killing rate of TU686 cells. The phagocytosis rate of TU686 cells was observed.

The Edu positive cell rates in control group, baicalein group, Vector group and CD47 group were (36.24±2.74)%, (13.33±1.93)%, (14.22±1.48)% and (27.80±2.74) %, respectively; the apoptosis rates were (3.94±0.40)%, (28.40±1.76)%, (26.60±1.41)% and (12.33±0.84)%, respectively; the relative expressions of CD47 protein were 1.00±0.11, 0.42±0.07, 0.44±0.06 and 1.21±0.12, respectively; the relative expression levels of CyclinD1 protein were 0.86±0.08, 0.37±0.05, 0.36±0.04 and 0.74±0.08, respectively; the relative expression levels of cleaved cysteine aspartate proteinase-7(Cl-Caspase-7) protein were 0.35±0.04, 0.99±0.12, 1.00±0.11 and 0.50±0.06, respectively; the killing rates of human peripheral lymphocytes to TU686 cells (1∶1 ratio) were (10.61±1.19)%, (32.02±2.27)%, (31.86±2.06)% and (14.39±1.07)%, respectively; the phagocytosis rates were (6.35±0.71)%, (11.99±1.64)%, (12.03±0.76)% and (7.06±0.57)%, respectively. The above indicators, baicalein group compared with the control group, Vector group compared with CD47 group, the differences were statistically significant (P<0.05, P<0.01, P<0.001).

Baicalein may induce the apoptosis of laryngeal carcinoma cells and inhibit the immune escape of laryngeal carcinoma cells by inhibiting the expression of CD47, thus slowing down the progression of laryngeal carcinoma.

Study on the long non-coding RNA (lncRNA) LINC00922 regulating secreted frizzled related protein 1 (SFRP1) to inhibit the malignant progression of human oral mucosal fibroblasts (hOMF) induced by arecoline.

Cells were divided into blank control (NC) group (hOMF cells were not treated in any way), model group (60 mg·L^-1 arecoline treatment), oe-LINC02147 group (60 mg·L^-1 arecoline treatment, transfected with overexpression of LINC02147 vector), si-SFRP1 group (60 mg·L^-1 arecoline treatment, transfected with overexpression of LINC02147 vector, transfected with SFRP1 inhibitor vector). Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of SFRP1 mRNA in each group of cells; immunofluorescence was used to detect the positive expression of alpha-smooth muscle actin (α-SMA) and vimentin in each group of cells; 5-ethynyl-2′-deoxyuridine was used to detect the proliferation rate of each group of cells; dichlorodihydrofluorescein diacetate fluorescence probe method was used to detect the content of reactive oxygen species (ROS) in each group of cells.

The relative expression levels of SERP1 mRNA in model group and oe-LINC02147 group were 1.00±0.08 and 3.75±0.59, respectively; the cell proliferation rates of NC group, model group, oe-LINC02147 group and si-SFRP1 group were (43.61±6.97)%, (12.98±4.27)%, (38.66±5.12)% and (15.73±5.42)%, respectively; ROS content were (9.42±1.73)%, (36.58±6.16)%, (12.89±2.08)% and (33.45±5.76)%, respectively; α-SMA positive expression were 1.00±0.13, 5.02±1.46, 2.36±0.48 and 4.37±0.97, respectively; the positive expressions of vimentin were 1.00±0.15, 4.63±1.51, 1.98±0.85 and 3.92±1.36, respectively. The above indexes in the model group were compared with the NC group, the above indexes in the oe-LINC02147 group were compared with the model group, and the above indexes in the si-SFRP1 group were compared with the oe-LINC02147 group, and the differences were statistically significant (all P<0.001).

LINC02147 may inhibit the malignant progression of arecoline-induced human oral mucosa fibroblasts by regulating SFRP1.

To investigate the role of miRNA-633 in targeting the regulation of bone morphogenetic protein (BMP) and Smad protein pathways in promoting the proliferation and differentiation of dental pulp stem cells into dentin.

Human dental pulp stem cells were randomly divided into control, ov-miRNA-633, NC, anti-miRNA-633 and cotransfection groups. The ov-miRNA-633 and control groups were transfected with miRNA-633 overexpression vector and corresponding control blank vector, respectively. The anti-miRNA-633 and NC groups were transfected with miRNA-633 knockout vector and corresponding control blank vector, respectively. The cotransfection group was transfected with miRNA-633 overexpression vector + shRNA-N-Cadherin. Cell proliferation was detected by CCK-8 method. The expression levels of N-Cadherin were detected by real-time polymerase chain reaction. The expression levels of phosphorylated Smad 1/5/8 (p-Smad 1/5/8) were detected by Western blotting.

The optical density values on the 7^th day of the control, ov-miRNA-633, NC, anti-miRNA-633 and cotransfection groups were 1.65±0.05, 1.79±0.08, 1.55±0.05, 1.19±0.08 and 1.76±0.07; the relative expression levels of N-Cadherin mRNA were 1.09±0.03, 0.63±0.03, 1.06±0.04, 1.31±0.09 and 0.46±0.06; the relative expression levels of p-Smad 1/5/8 protein were 0.79±0.05, 1.28±0.08, 0.80±0.09, 0.62±0.06 and 1.09±0.18, respectively. The differences of above indexes were statistically significant between the ov miRNA-633 group and the control group (P<0.05, P<0.01). And the differences of above indexes were statistically significant between the cotransfection group and the anti miRNA-633 group (all P<0.05).

miRNA-633 could promote the proliferation and differentiation of dental pulp stem cells into dentin by inhibiting N-cadherin expression, activating the BMPs/Smad pathway.

To investigate the efficacy of the hypoxia-inducible factor-1α (HIF-1α) inhibitor PX-478 in improving radiation-induced apoptosis in cardiomyocytes and to elucidate its molecular mechanisms.

H9c2 cells were divided into blank group, model group, experimental-L group and experimental-H group. The experimental-L, -H groups were cultured with PX-478 at concentrations of 5 and 10 mol·L^-1, respectively, while the other groups were cultured in normal medium. After 24 h of culture, all groups except the blank group were irradiated with 6 Gy X-rays to establish a model of radiation-induced cardiac injury and were subsequently cultured for another 24 h. Cell viability was assessed using the cell counting kit-8 assay; relative protein expression levels were determined by Western blotting; and apoptosis was detected using Annexin V/PI flow cytometry.

The relative expression levels of HIF-1α protein in the blank group, model group, experimental-L group and experimental-H group were 0.89±0.01, 1.05±0.01, 0.64±0.02 and 0.52±0.02; the relative expression levels of aquaporin-1 (AQP1) protein were 0.79±0.02, 0.94±0.02, 0.74±0.01 and 0.59±0.01; AQP4 protein levels were 0.89±0.01, 1.03±0.01, 0.68±0.01 and 0.50±0.01; B-cell lymphoma-2 (Bcl-2) protein levels were 0.78±0.02, 0.58±0.02, 1.00±0.03 and 0.82±0.03; Bcl-2-associated X protein (Bax) levels were 0.66±0.01, 0.96±0.01, 0.77±0.01 and 0.27±0.03; Caspase-3 levels were 0.83±0.01, 1.10±0.01, 0.71±0.02 and 0.30±0.01; the apoptosis rates were (4.05±0.60)%, (17.82±0.63)%, (9.35±0.41)% and (9.07±0.57)%, respectively. The above indicators in the blank, experimental-L, experimental-H groups showed statistically significant differences compared to the model group (all P<0.05).

PX-478 can improve radiation-induced cardiomyocyte edema and reduce apoptosis by inhibiting the abnormal activation of the HIF-1α/AQPs axis in H9c2 cells after irradiation, thereby regulating fluid metabolism.

To investigate the antitumor activity and mechanism of a pyrazole [1,5-a]pyrimidine derivative (BPPA) on human tongue squamous cell carcinoma Cal33 cells.

Cal33 cells were divided into blank group (normal culture), experimental-L, -M, -H groups (1, 2.5 and 5 μmol·L^-1BPPA) and combined group [2.5 μmol·L^-1BPPA and 5 mmol·L^-1 N-acety-L-cysteine (NAC)]. Cell viability was determined by thiazole blue assay. Cell apoptosis was measured using flow cytometry, while apoptosis-related protein expression levels were determined by Western blot analysis. Changes in reactive oxygen species and mitochondrial membrane potential were evaluated using immunofluorescence assay.

The survival rates of Cal33 cells in blank, experimental-L,-M,-H and combined groups were (99.56±0.91)%, (58.31±2.31)%, (47.93±1.67)%, (29.35±4.11)% and (70.27±1.21)%, respectively; cell apoptotic rates were (8.07±1.01)%, (44.04±0.94)%, (49.85±1.75)%, (66.79±0.83)% and (24.33±1.04)%, respectively; the relative fluorescence intensities of reactive oxygen species (ROS) were 1.23±0.21, 3.37±0.35, 15.53±1.46, 20.28±1.24 and 5.59±0.52, respectively; the mitochondrial membrane potential red fluorescence/green fluorescence values were 4.69±0.11, 4.24±0.12, 0.86±0.16, 0.46±0.05 and 2.99±0.11, respectively. Compared with blank group, the above indexes in the experimental-L, -M, -H groups were statistically significant (P<0.01, P<0.001). Compared with experimental-M group, the above indexes in combined group were statistically significant (P<0.01, P<0.001). The relative levels of pro-apoptotic B-cell lymphoma-2 (Bcl-2)-Associated X protein (Bax) in blank, experimental-L,-M,-H groups were 1.00±0.02, 1.94±0.03, 3.73±0.06 and 4.64±0.08, respectively; the relative levels of anti-apoptotic protein Bcl-2 were 1.00±0.02, 0.75±0.04, 0.62±0.02 and 0.46±0.03, respectively. Compared with blank group, the above indexes in the experimental-L, -M, -H groups were statistically significant (P<0.01, P<0.001).

BPPA exhibits anti-head and neck cancer activity by ROS mediating the decrease in mitochondrial membrane potential, thereby inducing apoptosis.

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.

Probing whether salivary acid-binding immunoglobulin-like agglutinin-15 (Siglec-15) promotes hepatocellular carcinoma proliferation and migration by regulating the signal transducer and activator of transcription 1/3 (STAT1/STAT3) pathway.

SMMC-7721 and BEL-7402 cells were divided into empty vector groups: S-NC and B-NC groups (NC siRNA was transfected into SMMC-7721 and BEL-7402 cell, respectively), Siglec-15 knockdown expression group: S-si-Siglec-15-3 and B-si-Siglec-15-3 groups (Siglec-15-3 siRNA was transfected into SMMC-7721 and BEL-7402 cell, respectively). The proliferation ability of the cells were detected by methyl thiazolyl tetrazolium (MTT); the longitudinal and lateral migration ability of the cells were detected by Transwell and scratch assay; the expression of STAT3, phosphorylation of STAT3 (p-STAT3), STAT1, phosphorylation of STAT1 (p-STAT1), Siglec-15 was detected by Western blot.

Cell viability values at 24 h in the S-NC group, S-si-Siglec-15-3 group, B-NC group and B-si-Siglec-15-3 group were 0.93±0.01, 0.87±0.03, 0.96±0.03 and 0.83±0.02, respectively; the vertical migration rates of cells were 100.00%, 36.40%, 100.00% and 52.20%, respectively; the healing rate of cell scratches at 24 h were (0.76±0.02)%, (0.53±0.02)%, (0.44±0.02)% and (0.36±0.03)%, respectively; STAT3 protein expression levels were 1.11±0.05, 0.66±0.05, 1.07±0.14 and 0.49±0.04, respectively; p-STAT3 protein expression levels were 1.07±0.04, 0.16±0.06, 0.78±0.05 and 0.32±0.03, respectively; STAT1 protein expression levels were 1.32±0.04, 0.71±0.04, 0.91±0.03 and 0.61±0.04, respectively; p-STAT1 protein expression levels were 0.99±0.04, 0.29±0.05, 0.67±0.04 and 0.20±0.06, respectively; Siglec-15 protein expression levels were 1.51±0.04, 0.93±0.05, 0.73±0.02 and 0.12±0.01, respectively. The differences between the S-si-Siglec-15-3 group and the S-NC group, between the B-si-Siglec-15-3 group and the B-NC group were statistically significant in all comparisons (P<0.05, P<0.01, P<0.001).

Siglec-15 promotes the proliferation and migration ability of hepatocellular carcinoma cells through the STAT1/STAT3 pathway.

To investigate the effect of venetoclax (Vene) on cell proliferation and apoptosis in acute myeloid leukemia (AML) by regulating the microRNA-410-3p (miR-410-3p)/high mobility group protein B1 (HMGB1) axis.

THP1 cells were randomly divided into control group (normal culture), experimental group (100 nmol·L^-1 Vene treatment), inh-NC group (experimental group + transfection of inh-miR-410-3p negative control), inh-miR-410-3p group (experimental group + transfection of inh-miR-410-3p), inh-NC combined with sh-NC group (inh-NC group + transfection of sh-HMGB1 negative control), inh-miR-410-3p combined with sh-NC group (inh-miR-410-3p group + transfection of sh-HMGB1 negative control), sh-HMGB1 group (inh-miR-410-3p group + transfection of sh-HMGB1). The relative expression levels of miR-410-3p and HMGB1 mRNA were detected by real-time quantitative polymerase chain reaction; immunofluorescence assay was used to detect the positive expression of HMGB1; 5-ethynyl-2′-deoxyuridine (EdU) was used to detect cell proliferation; Western blot was used to detect the relative expression levels of B lymphocytoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax).

The relative expression levels of miR-410-3p in the control group, experimental group, inh-NC group, inh-miR-410-3p group, inh-NC combined with sh-NC group, inh-miR-410-3p combined with sh-NC group and sh-HMGB1 group were 1.00±0.15, 3.76±0.31, 3.64±0.33, 1.69±0.20, 1.00±0.17, 0.42±0.06, 0.89±0.07, respectively; the relative expression levels of HMGB1 mRNA were 1.00±0.13, 0.62±0.07, 0.65±0.06, 0.93±0.11, 1.00±0.15, 1.93±0.21, 1.14±0.16, respectively. The relative fluorescence levels of HMGB1 in the control group, experimental group, inh-NC group and inh-miR-410-3p group were 1.00±0.16, 0.55±0.07, 0.58±0.08, 0.82±0.14, respectively. The cell proliferation rates of inh-NC combined with sh-NC group, inh-miR-410-3p combined with sh-NC group and sh-HMGB1 group were (11.46±1.95)%, (37.82±5.31)%, (16.14±3.05)%, respectively; the relative expression levels of Bcl-2 protein were 1.00±0.14, 4.17±0.39, 1.33±0.18, respectively; the relative expression levels of Bax protein were 1.00±0.16, 0.32±0.08, 0.91±0.13, respectively. The differences of above indexes were statistically significant between control group and the experimental group, between inh-NC group and the inh-miR-410-3p group, between inh-NC combined with sh-NC group and inh-miR-410-3p combined with sh-NC group, between inh-miR-410-3p combined with sh-NC group and the the sh-HMGB1 group (all P<0.001).

Vene can inhibit the proliferation of AML cells and induce apoptosis of AML cells by regulating the miR-410-3p/HMGB1 axis.

To investigate the mechanism of action of harmine (HM) in anti-Echinococcus granulosus (E.g) based on non-targeted metabolomics.

The aseptically cultured fine-grained E.g was divided into blank group (KB group, conventional culture), solvent group (DMSO group, DMSO 2 μL) and administration group (HM group, 20 mmoL·L^-1 HM solution 2 μL). Survival rate was observed by eosin staining after 48 h of intervention and the ultrastructural changes were observed by scanning electron microscopy, respectively. Meanwhile, non-targeted metabolomics analysis was performed based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) technology on each group of E.g to screen the differential metabolites and explore the effect of harmine on the metabolic profile of E.g.

Eosin staining and scanning electron microscopy results showed that harmine had a significant inhibitory effect on E.g in vitro. Metabolomics results showed that there were a total of 15 metabolites with significant differences between the harmine and blank groups (all P<0.05). Enrichment of the differential metabolites by Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that harmine mainly affected the metabolic pathways of amino acid metabolism, fatty acid metabolism and nucleotide metabolism in E.g.

Harmine had a significant inhibitory effect on E.g, the mechanism of which may be related to the regulation of amino acid metabolism, fatty acid metabolism and nucleotide metabolism pathways, which can provide a new way of thinking for the development of the subsequent anti-cystic echinococlosis drug targets.

To investigate the effect and mechanism of loganin on retinopathy in diabetic retinopathy (DR) rats.

DR rats were established by injection of streptozotocin and high glucose and high fat. They were randomly grouped into model group (0.9% NaCl), experimental -L group, experimental-H group (50, 100 mg·kg^-1 loganin), combined group [100 mg·kg^-1 loganin+10 mg·kg^-1 lysophosphatidic acid (LPA)] and 10 normal rats were taken as control group (0.9% NaCl). After the intervention, retinal histomorphology, the levels of inflammatory factors and oxidative stress, apoptosis of ganglion cells, and the expression of Ras homologous gene family member A (RhoA) and Rho associated coiled coil-forming kinase (ROCK) proteins in retinal tissue were measured in turn.

The number of retinal ganglion cells in experimental -L, -H groups, combined group, model group and control group were 19.75±1.90, 24.32±2.15, 17.80±1.94, 15.44±1.65 and 28.30±2.02; the levels of interleukin-6 were (85.67±8.61), (68.88±6.91), (98.52±9.88), (108.24±10.83) and (62.08±6.22) ng·L^-1; the levels of tumor necrosis factor -α were (150.24±15.11), (110.38±11.06), (186.94±18.77), (200.05±20.08) and (105.34±10.55) ng·L^-1; the levels of malondialdehyde were (7.52±0.78), (4.76±0.48), (9.52±0.96), (10.85±1.09) and (4.58±0.46) μmol·mg^-1; the superoxide dismutase activities were (62.05±6.21), (78.22±7.83), (52.11±5.23), (50.21±5.04) and (79.61±7.98) U·mg^-1; the apoptosis rates of ganglion cells were (12.71±1.06)%, (6.98±0.93)%, (14.69±1.30)%, (19.50±1.42)% and (2.15±0.38)%; the relative expression levels of RhoA protein were 0.81±0.09, 0.42±0.05, 1.08±0.11, 1.16±0.12 and 0.38±0.04; the relative expression levels of ROCK protein were 1.28±0.13, 0.77±0.08, 1.72±0.18, 1.85±0.19 and 0.63±0.07, respectively. Compared with the model group, the above indexes of the control group, experimental -H group and combination group had statistical significance (all P<0.05).

Loganin may improve retinopathy in DR rats by inhibiting the activation of RhoA/ROCK pathway, inhibiting inflammation and oxidative stress response.

To explore effect and mechanism of microRNA 142a-3p (miR-142a-3p) on adriamycin-induced nephropathy (AN).

BALB/c mice were randomly divided into normal group and model group. The model group was injected with 10.5 mg·kg^-1 doxorubicin at a time through the tail vein, and the normal group was injected with equal volume 0.9% NaCl by the same method. After 28 days of feeding, both sides of the kidney tissues were taken for experiment. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-142a-3p in the renal tissues. The expression levels of autophagy related protein 16-like protein 1 (Atg16l1) and inflammatory NOD-like receptor heat protein domain associated protein 3 (NLRP3), interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the renal tissues were detected by Western blotting. Human embryonic kidney 293T cells were divided into Atg16l1-WT+NC transfection group (transfected pmirGLO-Atg16l1-WT and NC mimics) and Atg16l1-WT+miRNA-142a-3p group (transfected pmirGLO-Atg16l1-WT and miR-142a-3p mimics). Dual luciferase assay was used to detect the targeted regulation of miR-142a-3p on Atg16l1.

The expression levels of miR-142a-3p in kidney tissues of normal group and model group were 1.20±0.27 and 2.02±0.14; the expression levels of Atg16l1 were 0.81±0.13 and 0.57±0.12, NLRP3 were 0.49±0.11 and 0.82±0.14; IL-1β were 0.55±0.11 and 0.84±0.08; IL-18 levels were 0.41±0.15 and 0.74±0.09, respectively, and the above indexes in the model group were significantly different from those in the normal group (all P<0.05). The relative luciferase activity in Atg16l1-WT+NC transfection group and Atg16l1-WT+miRNA-142a-3p transfection group were 1.26±0.07 and 0.92±0.10, respectively, with statistical significance (all P<0.05).

MiR-142a-3p down-regulates the expression of target protein Atg16l1 in renal tissue of adriamycin nephropathy mice, which activates NLRP3 pathway of inflammatory bodies and promotes the progressive development of adriamycin-induced nephropathy.

To explore the therapeutic effects and mechanisms of Dunhuang Xiexin decoction on mice with ulcerative colitis (UC).

Mice were randomly divided into blank group (0.9% NaCl), model group (0.9% NaCl) and experimental-L, -M, -H groups (2.93, 5.85, 11.70 g·kg^-1 Dunhuang Xiexin decoction water extracts) with 10 cases per group for 7 days. Meanwhile, apart from the blank group, the other four groups of mice were allowed adlibitum access to drinking water containing 3% sodium dextran sulfate for 7 consecutive days to establish the UC model. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in mouse serum were determined by enzyme-linked immunosorbent assay. The expression levels of occludin, zonula occludens-1 (ZO-1) and phospho nuclear factor kappa B p65 (p-NF-κB p65) in colonic tissues was detected by Western blot.

The serum TNF-α levels in the experimental- M, - H groups, model group and blank group were (397.57±33.05), (389.41±22.57), (472.19±18.70) and (355.92±31.86) pg·mL^-1; the IL-1β levels were (73.06±18.38), (62.60±9.80), (98.94±27.50) and (55.26±18.14) ng·mL^-1; the IL-6 levels were (153.23±32.96), (148.12±23.53), (239.35±50.99) and (131.36±27.58) pg·mL^-1; the relative expressions levels of occludin protein in colon tissues were 0.80±0.13, 1.03±0.24, 0.57±0.15 and 1.10±0.03; the relative expressions levels of ZO-1 protein were 0.90±0.21, 1.09±0.10, 0.73±0.16 and 1.29±0.03; the relative expressions levels of p-NF-κB p65 protein were 0.75±0.12, 0.53±0.08, 1.15±0.19 and 0.43±0.21, respectively. There were significant differences between the experimental- H group and the model group (P<0.05).

Dunhuang Xiexin decoction may improve ulcerative colitis in mice by repairing the intestinal barrier and inhibiting the NF-κB signaling pathway to reduce the release of inflammatory factors.

To observe the effect of Tetrahydropalmatine on the epidermal growth factor receptor / phosphatidylinositol 3-kinase/protein kinase B (EGFR/PI3K/AKT) signaling pathway in endometriosis dysmenorrhoea SD rats.

The endometriosis dysmenorrhoea model was replicated by auto-transplantation in 60 female SD rats of SPF grade. After successful modelling, the rats were randomly divided into model group, control group and experimental -L, -M, -H groups according to body mass, with 12 rats in each group; and another 12 normal rats were taken as the blank group. The blank and model groups were given 10 mL·kg^-1 0.9% NaCl by gavage, and the control group was given 0.25 mg·kg^-1 progesterone suspension by gavage. The experimental-L, experimental-M, experimental-H groups were given 10, 20 and 40 mg·kg^-1 Tetrahydropalmatine suspension by gavage, respectively. Six groups of rats were administered once daily for 4 weeks. After the last administration, 2 U of oxytocin was given to induce contractions, and the rats were observed for torsional responses. The serum levels of tumor necrosis factor -α (TNF-α), epidermal growth factor (EGF), and EGFR were measured by enzyme-linked immunosorbent assay in each group of rats, and the expression levels of EGFR, PI3K and AKT proteins in ectopic endometrial tissues were detected by Western blotting.

The number of twists in the experimental -M, -H groups and control group, model group, blank group were 9.25±1.42, 8.33±1.88, 11.17±2.41, 28.67±2.15 and 0; the inhibition rates were 67.74%, 70.95%, 61.05%, 0 and 0; serum TNF-α levels were (281.96±13.06), (278.75±10.39), (282.12±14.47), (303.59±9.09) and (274.26±15.33) ng·L^-1; serum EGF levels were (313.82±13.23), (308.26±10.90), (311.39±19.52), (336.04±17.60) and (301.67±27.17) pg·mL^-1; serum EGFR levels were (315.71±7.56), (311.43±11.04), (313.75±7.26), (333.56±14.22) and (307.86±17.94) ng·L^-1; the relative expression levels of EGFR protein were 1.60±0.39, 1.26±0.30, 1.40±0.40, 2.08±0.41 and 1.00±0.22; the relative expression levels of PI3K protein were 1.60±0.42, 1.21±0.18, 1.27±0.24, 2.01±0.41 and 1.00±0.19; the relative expression levels of AKT protein were 1.27±0.18, 1.11±0.10, 1.27±0.16, 1.64±0.28 and 1.00±0.07, respectively. Statistically significant differences were found between the above indicators in the experimental -M, -H groups compared to the model group (P<0.01, P<0.05).

Tetrahydropalmatine may play a therapeutic role in endometriosis dysmenorrhoea by interfering with the EGFR/PI3K/AKT signaling pathway.

To evaluate the pharmacokinetic characteristics and safety of delafloxacin, a new fluoroquinolone drug, in Chinese healthy subjects, and to evaluate the expected microbiological efficacy of delafloxacin in treating infections caused by Staphylococcus aureus and Streptococcus pneumoniae through pharmacokinetic/pharmacodynamic analysis.

This trial consists of two parts. The first part is a randomized, double-blind, placebo-controlled, single-dose/multiple-dose administration trial with a dose range of 150-450 mg. The second part is a randomized, open-label, double-period, self-crossover trial comparing the pharmacokinetic similarities between a 300 mg intravenous infusion of the test drug and the reference drug. Combined with the in vitro pharmacodynamic data of delafloxacin against Staphylococcus aureus and Streptococcus pneumoniae clinically isolated in China, the Monte Carlo simulation method was used to analyze the probability of target attainment and cumulative fraction of response of the 300 mg q12 h intravenous infusion over 60 min and to evaluate the expected microbiological efficacy.

After administering 150, 300 and 450 mg of delafloxacin to Chinese healthy subjects in single doses, the C_max, AUC_0-t and AUC_0-∞ increase proportionally with the dose. The apparent volume of distribution ranged from 45.79 to 144.38 L. The elimination half-life of each dose group ranged from 2.99 to 11.87 h. The cumulative urinary excretion rates of (47.69±8.11)% and (73.71±9.32)% were observed for single doses of 300 and 450 mg, respectively, suggesting that the primary route of excretion was renal. The 90% confidence interval of C_max, AUC_0-t and AUC_0-∞ of test drug over reference drug after single-dose intravenous infusion are all within 80.00%-125.00%. After reaching steady state with multiple-dose administration in the 300 mg group, the plasma exposure level was similar to that of the single-dose administration group.

Single-dose intravenous infusion of 150-450 mg delafloxacin in healthy subjects showed linear pharmacokinetic characteristics, and there was no accumulation after 300 mg q12 h administration. Adverse effects were mild, indicating good safety, and good microbiological efficacy.

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 explore the effect of honey-processed Hedysari Radix on the metabolism of short-chain fatty acids (SCFAs) in the cecum of rats with spleen qi deficiency.

A total of 48 SPF male SD rats were randomly divided into blank group, model group, control group and experimental group, with 8 rats in each group. The blank group was fed normally, drank water and ate freely for 15 days, and the other groups used the three-factor composite modeling method of bitter cold diarrhea, overwork and hunger and satiety to construct a spleen qi deficiency model rats for 15 days. After the successful replication of the model, the rats in the control group were given 62.5 mg·kg^-1 bifidobacterium Lactobacillus triple viable tablets suspension, the experimental group was given 12.6 g·kg^-1 honey-processed Hedysari Radix decoction, and the blank group was given the same dose of distilled water, and the model group continued to model for 15 days. Gas chromatography-mass spectrometry (GC-MS) was used to determine the contents of SCFAs in the cecal contents of rats in each group.

The contents of acetic acid, isobutyric acid, butyric acid, isovaleric acid and caproic acid in the cecal contents of rats in the blank group were (3 706.24±401.84), (99.34±39.11), (2 567.95±529.44), (86.50±54.11) and (393.14±103.33) μg·g^-1, respectively. Compared with the blank group, the contents of acetic acid, isobutyric acid, butyric acid, isovaleric acid and caproic acid in the cecum contents of spleen-qi deficiency rats in the model group were significantly reduced, which were (3 049.48±590.62), (67.27±12.99), (2 058.00±417.46), (43.10±11.12) and (27.98±14.40) μg·g^-1, respectively (P<0.05, P<0.01). Compared with the model group, the contents of isovaleric acid and caproic acid in the cecum contents of rats in the experimental group were significantly increased, which were (90.59±26.03) and (60.05±19.89) μg·g^-1, respectively (all P<0.01).

Honey-processed Hedysari Radix can play a role in strengthening the spleen and replenishing qi by improving the metabolism level of cecal contents, regulating the metabolism levels of SCFAs in cecal contents, protecting the intestinal mucosal barrier, and reducing intestinal inflammation.