To evaluate the efficacy, safety, and economy of trastuzumab emtansine (T-DM1) in the treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer based on the rapid health technology assessment methodology, and to provide a reference for the rational use of the drug in the clinic.

A systematic search of Chinese and English databases such as PubMed, Embase, the Cochrane Library, CNKI, Wanfang, SinoMed, etc. was performed to screen the literature according to the inclusion and exclusion criteria, extract the data, evaluate the quality of the literature, and qualitatively analyze the results.

T-DM1 had comparable or even superior efficacy in terms of progression-free survival (PFS) and overall survival (OS) compared with conventional anti-HER2 treatment regimens as well as other chemotherapeutic regimens. Some regimens, such as docetaxel+trastuzumab+patuximab, and pyrrolitinib+capecitabine, might be superior to T-DM1 in terms of PFS and OS. Adverse effects of T-DM1 were mainly liver function abnormalities and thrombocytopenia, and overall the safety profile was better, with a lower probability of serious adverse effects. In terms of economy, T-DM1 was more favorable than T-Dxd, and further evaluation was still needed compared with other regimens.

T-DM1 has favorable efficacy and safety, with economics to be further evaluated.

To investigate the effect of ganoderma lucidum polysaccharides (GLPS) on ferroptosis of hippocampal neuronal (HT22) cell lines induced by hydrogen peroxide (H₂O₂) and its mechanism.

The H₂O₂-induced HT22 cell injury model was first established in vitro. HT22 cells were divided into normal group (conventional culture), H₂O₂ group (200 μmol·L^-1 H₂O₂), GLPS group (200 μmol·L^-1 H₂O₂+100 μg·mL^-1 GLPS), H₂O₂+Fin56 group (200 μmol·L^-1 H₂O₂+5 μmol·L^-1 Fin56), H₂O₂+Fin56+GLPS group (200 μmol·L^-1 H₂O₂+5 μmol·L^-1 Fin56+100 μg·mL^-1 GLPS). The oxidative stress markers were detected by enzyme-linked immunosorbent assay (ELISA); the protein expression levels of iron death markers, nuclear factor erythroid2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western blot.

The contents of malondialdehyde (MDA) in normal group, H₂O₂ group, GLPS group, H₂O₂+Fin56 group and H₂O₂+Fin56+GLPS group were (5.56±0.61), (15.53±0.83), (6.51±0.29), (20.92±1.03) and (13.65±0.70) nmol·mL^-1; the contents of superoxide dismutase (SOD) were (37.93±1.37), (22.48±0.59), (37.81±2.56), (16.10±2.28) and (22.21±2.99) μg·mL^-1; Ferritin protein expression levels were 1.52±0.03, 1.22±0.07, 1.42±0.06, 0.64±0.02 and 0.93±0.13; GPX4 protein expression levels were 3.29±0.34, 1.91±0.18, 2.99±0.22, 1.13±0.07 and 2.45±0.05; Nrf2 protein expression levels were 0.90±0.01, 2.24±0.02, 2.97±0.07, 2.45±0.07 and 2.76±0.11; HO-1 protein expression levels were 1.58±0.02, 1.76±0.04, 2.29±0.06, 1.67±0.02 and 2.03±0.06, respectively. H₂O₂ group was compared with normal group and H₂O₂+Fin56 group, GLPS group was compared with H₂O₂ group, H₂O₂+Fin56+GLPS group was compared with H₂O₂+Fin56 group and GLPS group, the differences were statistically significant (P<0.05, P<0.01).

GLPS can improve lipid peroxide accumulation and iron metabolism disorder induced by H₂O₂ in HT22 cells by activating Nrf2/HO-1 pathway, thereby inhibiting the occurrence of ferroptosis.

To investigate the mechanism of action of bezafibrate (BEZ) targeting nuclear factor of activated T cells 5 (NFAT5) through microribonucleic acid (miR)-486-5p on the kidney tissues of mice with diabetic nephropathy.

Db/m mice were used as control group. Db/db mice were used to construct a diabetic nephropathy model, which was divided into 4 groups according to the random number table method: Model group, experimental group (75 mg·kg^-1·d^-1 BEZ), miR-486-5p antagomir group (75 mg·kg^-1·d^-1 BEZ+10 mg·kg^-1 miR-486-5p antagomir), sh-NFAT5 group (75 mg·kg^-1·d^-1 BEZ+10 mg·kg^-1 miR-486-5p antagomir+recombinant adenovirus containing NFAT5 knockdown plasmid). The kit was used to detect the levels of renal function and oxidative stress in mice; and the expression levels of glucose metabolism and renal fibrosis-related proteins in renal tissues of mice in each group were detected by Western blot.

The levels of malondialdehyde (MDA) in the control group, model group, experimental group, miR-486-5p antagomir group, and sh-NFAT5 group were (2.78±0.56), (4.96±0.97), (3.02±0.54), (4.51±0.79) and (3.24±0.58) nmol·mg^-1, respectively; the levels of aldose reductase (AR) were 1.00±0.12, 3.61±0.43, 1.82±0.29, 3.09±0.58 and 2.25±0.47, respectively; the levels of pyruvate dehydrogenase (PDH) were 1.00±0.11, 0.53±0.10, 0.91±0.15, 0.64±0.12 and 0.82±0.14, respectively; the levels of pyruvate dehydrogenase E1 subunit α1 (PDHA1) were 1.00±0.14, 0.36±0.07, 0.83±0.16, 0.51±0.11 and 0.74±0.13, respectively; the levels of pyruvate dehydrogenase kinase (PDK) were 1.00±0.10, 2.59±0.52, 1.34±0.31, 2.11±0.43 and 1.56±0.39, respectively; the levels of transforming growth factor-β1 (TGF-β1) were 1.00±0.11, 3.15±0.52, 1.43±0.38, 2.72±0.43 and 1.89±0.57, respectively; the levels of fibronectin (FN) were 1.00±0.09, 2.84±0.57, 1.46±0.41, 2.59±0.52 and 1.73±0.49, respectively; the levels of collagen type I (Collagen I) were 1.00±0.13, 4.28±0.71, 2.03±0.46, 3.64±0.68 and 2.51±0.53, respectively. The above indicators of the control group were compared with the model group, the above indicators of the model group were compared with the experimental group, the above indicators of the experimental group were compared with the miR-486-5p antagomir group, and the above indicators of the miR-486-5p antagomir group were compared with the sh-NFAT5 group. The differences were statistically significant (P<0.05, P<0.01, P<0.001).

BEZ can effectively protect the kidney tissue of mice with diabetic nephropathy, and the mechanism may be realized through the miR-486-5p/NFAT5 signaling pathway.

To establish a method for the determination of carfilzomib in rat plasma by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and to investigate the pharmacokinetic characteristics of carfilzomib in rat plasma.

The rat plasma samples were processed by a protein precipitation approach using methanol∶acetonitrile (1∶1, v/v). Chromatographic column: Thermo Scientific^TM Hypersil GOLD^TM C₁₈ Column (2.1 mm×50.0 mm, 3 μm); mobile phase: 2 mmol·L^-1 ammonium acetate-0.02% formic acid water (A)-methanol (B) in gradient elution mode; flow rate: 0.45 mL·min^-1; injection volume: 5 μL. Electrospray ionization source in positive ion mode and multiple reaction monitoring were adopted. The specificity, standard curve and lower limit of quantification, residue effect, precision and extraction recovery rate, dilution reliability, matrix effect and stability of this method were examined. After a single intravenous injection of 4 mg·kg^-1 carfilzomib into 6 healthy male SD rats, blood was collected from the inner corner of the eye, and the concentration of carfilzomib in the plasma was detected. The pharmacokinetic parameters were calculated using DAS 3.0.

Carfilzomib exhibited good specificity and linearity within the range of 0.5 to 1 250.0 ng·mL^-1, with a standard curve of y=2.40×10^-2x+6.81×10^-2 (r=0.996 4), the quantitative limit of detection was 0.5 ng·mL^-1, the sample residues were 7.64% and 1.00% of the quantitative limit of detection and the internal standard, respectively, the intra-day and inter-day precision were ≤7.51% and ≤8.16%, respectively, the intra-day and inter-day accuracy were -4.54% to 5.14% and -4.41% to 8.26%, respectively, the extraction recovery were 92.49% to 108.33%, and the methodological evaluation results of sample dilution effect, matrix effect and stability were all in accordance with the requirements for the validation of biological sample analysis methods. The main pharmacokinetic parameters of carfilzomib were: C_max was (1.10×10⁶±5.45×10⁵) ng·L^-1, t_1/2 was (23.10±7.38) min, AUC_0-t was (1.85×10⁷±9.85×10⁶) ng·L^-1·min.

The approach formulated in this study is operationally facile, highly discriminatory, sensitive, precise, dependable, and is appropriate for the determination and analysis of carfilzomib in rat plasma specimens.

To investigate the in vitro inhibitory effects of microRNA-28-5p (miR-28-5p) targeting G antigen 12I antibody (GAGE12I) on the proliferation, migration, and invasion of gastric cancer cells.

SGC-7901 cell were randomly divided into miR-28-5p group (miR-28-5p mimic), miR-NC group (miR-28-5p negative control mimic), shGAGE12I group (GAGE12I knockout) and blank group (GAGE12I not knockout). Cell proliferation, migration, and invasion capabilities were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and invasion chambers. Bioinformatics analysis and luciferase activity assays were conducted to examine the interaction between miR-28-5p and GAGE12I.

The proliferation rates of miR-28-5p and miR-NC groups were (99.90±10.30)% and (48.25±4.15)%; the invasion rates were (145.57±14.52)% and (67.30±6.95)%; the mobility rates were (103.58±10.75)% and (43.18±4.26)%, respectively, the differences were statistically significant (all P<0.05). The proliferation rates of shGAGE12I group and blank group were (99.80±10.20)% and (35.50±3.58)%; the invasion rates were (142.70±13.65)% and (65.30±6.75)%; the mobility rates were (103.55±10.06)% and (48.38±4.52)%, respectively, the differences were statistically significant (all P<0.05). GAGE12I was the target of miR-28-5p.

MiR-28-5p negatively regulates GAGE12I and reduces the proliferation, invasion and migration of gastric cancer cells.

To investigate the effects of sodium aescinate on the differentiation of human umbilical cord mesenchymal stem cells (HUMSC) into neural-like cells and its possible mechanism.

HUMSC cells were randomly divided into blank group, experiment-L group, experiment-M group and experiment-H group. All the cells were cultured with neurobasal medium (NM) medium, cells in experiment-L group, experiment-M group and experiment-H group were treated with 1.00, 2.00 and 4.00 mg·L^-1 sodium aescinate, respectively. The expression levels of neuron-like cells markers and synaptic markers were detected by reverse transcription-polymerase quantitative chain reaction (RT-qPCR) and Western blot.

The relative mRNA expression levels of microtubule-associated protein 2 (MAP-2) in blank group, experiment-L group, experiment-M group and experiment-H group were 1.00±0.14, 1.26±0.08, 1.74±0.16 and 2.30±0.20, respectively; the relative mRNA expression levels of growth associated protein 43(GAP43) were 1.00±0.10, 1.14±0.15, 1.34±0.15 and 1.53±0.11, respectively; the relative expression levels of synaptophysin(SYN) mRNA were 1.00±0.09, 1.15±0.08, 1.32±0.12 and 1.48±0.13, respectively; the expression levels of neurofilament heavy chain(NF-H) protein were 0.41±0.04, 0.50±0.06, 0.71±0.06 and 1.21±0.09, respectively; postsynaptic density protein 95(PSD95) protein expression levels were 0.27±0.04, 0.41±0.06, 0.52±0.04 and 0.68±0.06, respectively; silent information regulator 1(SIRT1) protein expression levels were 0.31±0.04, 0.52±0.06, 0.67±0.06 and 0.80±0.10, respectively. The above indexes in experiment-L group, experiment-M group and experiment-H group were compared with blank group, the differences were all statistical significant (P<0.05, P<0.01); the above indexes compared among experiment-L group, experiment-M group and experiment-H group, the differences were all statistically significant (P<0.05, P<0.01).

Sodium aescinate may induce the differentiation of HUMSC into neural-like cells by regulating SIRT1 in vitro.

To explore the mechanism of tacrolimus mediating the protective effect on chronic glomerulonephritis (CGN) rats through regulating the expression of microRNA-145-5p (miR-145-5p) and modulating the C-X-C motif chemokine ligand 16/Ras homolog family member A/Rho-associated coiled-coil-containing protein kinase (CXCL16/RhoA/ROCK) pathway.

SD rats were randomly divided into the control group (administered an equal volume of 0.9% NaCl), model group (CGN model + equal volume of 0.9% NaCl), experimental group (CGN model + 3 mg·kg^-1·d^-1 tacrolimus) and combined group (experimental group + tail vein injection of 140 nmol·L^-1 miR-145-5p antagomir). Enzyme-linked immunosorbent assay was used to measure 24-hour urinary protein (PRO), blood urea nitrogen (BUN), and serum creatinine (SCr) levels. Real-time quantitative polymerase chain reaction was used to detect the relative expression level of miR-145-5p in rat kidney tissue; Western blotting was used to determine protein expression levels.

The 24-hour PRO levels in the control, model and experimental groups were (7.44±2.16), (85.29±17.35) and (49.81±9.52) mg, respectively; the BUN levels were (5.82±1.03), (9.65±1.78) and (6.97±1.14) mmol·L^-1, respectively; the SCr levels were (46.31±7.69), (93.57±16.94) and (58.72±8.36) μmol·L^-1, respectively. The relative expression levels of miR-145-5p in the control, model, experimental and combined groups were 1.00±0.14, 0.56±0.07, 0.83±0.12 and 0.68±0.09, respectively; the TNF-α levels were (116.42±14.53), (237.56±26.18), (164.79±18.35) and (205.12±21.64) pg·mL^-1, respectively; the IL-1β levels were (15.76±1.84), (52.41±6.27), (21.35±2.92) and (43.63±4.58) pg·mL^-1, respectively; the IL-6 levels were (26.28±3.47), (71.53±8.64), (38.92±5.06) and (59.78±6.21) pg·mL^-1, respectively; the CXCL16 expression levels were 1.00±0.12, 1.62±0.17, 1.23±0.14 and 1.45±0.15, respectively. Statistical analysis revealed significant differences between the model group and the control group, between the experimental group and the model group, and between the combined group and the experimental group for these indicators (P<0.05, P<0.01, P<0.001).

Tacrolimus can upregulate miR-145-5p, activate the CXCL16/RhoA/ROCK pathway, reduce inflammatory factors, and improve kidney damage in CGN rats.

To explore the effects of aloe-emodin on the proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of pathological scar fibroblasts, as well as its regulatory mechanisms.

Proliferative scar fibroblasts (HSFb) were randomly divided into the following groups: HSFb control group (normal culture), HSFb low-dose group (25.00 μg·mL^-1 aloe-emodin), HSFb medium-dose group (50.00 μg·mL^-1 aloe-emodin), HSFb high-dose group (100.00 μg·mL^-1 aloe-emodin), and HSFb-PFT-α group (100.00 μg·mL^-1 aloe-emodin + 20.00 μmol·L^-1 p53-specific inhibitor PFT-α). Keloid fibroblast (KFb) cells were randomly divided into the following groups: KFb control group (normal culture), KFb low-dose group (25.00 μg·mL^-1 aloe-emodin), KFb medium-dose group (50.00 μg·mL^-1 aloe-emodin), KFb high-dose group (100.00 μg·mL^-1 aloe-emodin), and KFb-PFT-α group (100.00 μg·mL^-1 aloe-emodin + 20.00 μmol·L^-1 p53-specific inhibitor PFT-α). Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, Western blotting was performed to detect the expression of p53 and EMT-related proteins, apoptosis was measured using the TUNEL assay.

The cell survival rates of the KFb control group, KFb low-dose group, KFb medium-dose group, and KFb high-dose group were (100.00±5.17)%, (84.13±8.34)%, (73.81±7.62)% and (54.59±3.47)%, respectively; the cell survival rates of the HSFb control group, HSFb low-dose group, HSFb medium-dose group, and HSFb high-dose group were (100.00±6.77)%, (83.50±6.08)%, (71.43±2.70)% and (61.80±4.79)%, respectively. The relative expression levels of p53 protein in the KFb control group, KFb low-dose group, KFb high-dose group, and KFb-PFT-α group were 0.31±0.04, 0.52±0.04, 0.76±0.06 and 0.38±0.05, respectively; the relative expression levels of E-cadherin protein were 0.35±0.04, 0.58±0.08, 0.76±0.13 and 0.41±0.06, respectively; the apoptosis rates were (4.82±0.59)%, (11.72±1.68)%, (20.36±1.93)% and (12.46±1.28)%, respectively; the relative expression levels of p53 protein in the HSFb control group, HSFb low-dose group, HSFb high-dose group, and HSFb-PFT-α group were 0.37±0.03, 0.48±0.05, 0.65±0.07 and 0.46±0.04, respectively; the relative expression levels of E-cadherin protein were 0.26±0.03, 0.46±0.05, 0.63±0.08 and 0.34±0.05, respectively; the apoptosis rates were (4.89±0.28)%, (13.98±0.83)%, (21.51±1.08)% and (12.95±1.10)%, respectively. The differences between the KFb low- and high-dose groups and the KFb control group, the KFb-PFT-α group and the KFb high-dose group, the HSFb low- and high-dose groups and the HSFb control group, and the HSFb-PFT-α group and the HSFb high-dose group were statistically significant (P<0.05, P<0.01, P<0.001).

Aloe-emodin may inhibit the proliferation of pathological fibroblasts, EMT, and induce apoptosis by regulating the p53-related signaling pathway.

To investigate the mechanism of quercetin in promoting muscle regeneration in acute skeletal muscle injury.

Satellite cells were randomly divided into blank group (conventional culture), hydrogen peroxide (H₂O₂) group (100 μmol·L^-1 H₂O₂ treated cells for 24 h), quercetin group (10 μmol·L^-1 quercetin treated cells for 24 h), H₂O₂+quercetin group (100 μmol·L^-1 H₂O₂+10 μmol·L^-1 quercetin treated cells for 24 h). Cell proliferation was detected by cell counting kit-8 (CCK-8) method; protein expression was detected by Western blot assay; mitochondrial reactive oxygen species (ROS) levels and related indicators of mitochondrial respiration were detected by kit.

The 24 h proliferation rates of cells in blank group, quercetin group, H₂O₂ group and H₂O₂+quercetin group were (100.00±4.27)%, (148.79±13.17)%, (81.70±3.19)% and (120.83±8.81)%, respectively; the relative expression levels of superoxide dismutase 1 (SOD1) protein were 0.64±0.09, 0.76±0.09, 0.24±0.03 and 0.43±0.06, respectively; the relative expression levels of myosin heavy chain (MyHC) protein were 0.61±0.05, 0.67±0.06, 0.32±0.03 and 0.47±0.06, respectively; the fluorescence intensities of mitochondrial ROS were (52.56±1.97), (48.46±4.05), (119.53±13.06) and (102.91±8.93) a.u., respectively; the catalase (CAT) levels were (28.66±2.18), (35.62±3.89), (18.13±1.78) and (23.97±2.72) μmol·mg protein^-1, respectively; mitochondrial respiratory chain (MRC) complex Ⅰ levels were (19.77±1.01), (23.28±2.48), (9.87±1.01) and (14.19±0.75) μmol·mg protein^-1, respectively. The above indexes in quercetin group and H₂O₂ group were compared with blank group, the above indexes in H₂O₂+quercetin group were compared with H₂O₂ group, the difference was statistically significant (P<0.05, P<0.01, P<0.001).

Quercetin can promote mitochondrial respiration by clearing mitochondrial ROS levels, improve oxidative damage, and then promote satellite cell proliferation, which can promote muscle regeneration in acute skeletal muscle injury.