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 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 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.

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 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.