Latest ArticlesA common carcinogenic mechanism in non-small cell lung cancer (NSCLC) is a jump mutation in exon 14 of the mesenchymal epithelial transition factor (MET) gene, which is commonly present in NSCLC cases and accelerates cancer progression. Clinical studies have shown that tepotinib, as the first oral tyrosine kinase inhibitor targeting MET, exhibits significant efficacy in advanced NSCLC, with an overall response rate (ORR) of 44.7% and a median progression free survival (PFS) of 8.9 to 12.2 months. Although drug resistance appears within 6 to 12 months after treatment, combined treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) can overcome some of the resistance caused by EGFR mutations and MET expansion. In addition, tepotinib has good safety in different patient populations, with common adverse reactions including peripheral edema, nausea, and diarrhea. Tepotinib significantly prolongs the PFS of patients. In addition, other novel MET-TKI such as carbamatinib and sevotinib have also shown good efficacy in the treatment of MET mutant NSCLC. This article summarizes the pharmacological effects, resistance mechanisms, adverse reactions, and clinical application progress of terbotinib in NSCLC.
To investigate the protective effect of hedysarum polybotrys polysacchcaide (HPS) on intestinal mucosal barrier in rats with splenic deficiency type diabetic gastroparesis.
The rat model of spleen deficiency DGP was prepared by multifactorial combined with low-dose intraperitoneal injection of Stretocin. The rats were randomly divided into blank group (pure water gavage), model group (pure water gavage), positive control group (0.09 g·kg-1 metformin hydrochloride sustained-release tablet) and experimental-H,-M,-L groups (0.20, 0.10, 0.05 g·kg-1 HPS), each group was administered by gavage once a day for 8 W. Measured blood glucose, diamine oxidase (DAO), lipopolysaccharides (LPS), D-lactate contents (D-LA) in serum by enzyme linked immunosorbent assay method; Claudin-1, Occludin, Zonula Occluden-1 (ZO-1) mRNA and protein expressions in lleal tissue were detected by reverse transcription-polymerase chain reaction and Western blot.
The blood glucose in the blank group, model group, positive control group, experimental-H,-M,-L groups were (5.04±0.40), (30.71±1.21), (18.63±6.72) and (19.90±3.30)mmol·L-1; the DAO were (49.56±6.13), (192.19±24.40), (130.63±19.90) and (120.24±17.53) pg·mL-1; the LPS were (41.11±4.56), (99.67±6.63), (64.51±8.59) and (63.07±4.89) ng·L-1; the D-LA were (506.45±52.22), (1 826.49±224.17), (1 166.47±121.78) and (1 344.82±130.65) μg·L-1; the relative expression levels of Claudin-1 mRNA were 1.03±0.32, 0.25±0.12, 0.94±0.40 and 0.71±0.21; the relative expression levels of Occludin mRNA were 1.07±0.48, 0.26±0.06, 1.23±0.42 and 0.99±0.47; the relative expression levels of ZO-1 mRNA were 1.00±0.13, 0.43±0.18, 0.85±0.07 and 0.69±0.08; the relative expression levels of Claudin-1 protein were 1.00±0.00, 0.21±0.19, 0.56±0.31 and 0.87±0.31; the relative expression levels of Occludin protein were 1.01±0.27, 0.38±0.11, 0.88±0.10 and 0.85±0.18; the relative expression levels of ZO-1 protein were 1.00±0.14, 0.43±0.04, 0.77±0.02 and 0.67±0.16. Compared with the the blank group, the above indexes in the model group had statistical significance (P<0.01, P<0.05); compared with the model group, the above indexes in the experimental-H had statistical significance (P<0.01, P<0.05).
HPS can reduce intestinal mucosal injury and maintain the integrity of the intestinal mucosal barrier in spleen deficiency DGP rats.
To investigate the intervention effect and mechanism of β-ecdyssterone on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) based on the regulation of autophagy by the adenosine 5′-monophosphate kinase-activated protein (AMPK)/mammalian target of rapamycin (mTOR).
BMSCs cells were divided into control group (normal culture), low-, middle- and high-dose groups (intervened with 0.01, 0.10 and 1.00 μmol·L-1 ecdysterone). The expression of cell genes was determined by real-time quantitative polymerase chain reaction (qRT-PCR); and the relative expression level of cell proteins was determined by immunofluorescence (IF).
The relative expression levels of alkaline phosphatase (ALP) mRNA in the control group, low-, middle and high-dose groups were 1.01±0.14, 1.22±0.05, 1.28±0.05, 1.59±0.20; the relative protein expression levels of Runt-related transcription factor 2 (RUNX2) mRNA were 1.00±0.07, 1.45±0.07, 2.11±0.32, 4.67±1.45; the relative protein expression levels of phosphorylated AMPK protein were 0.07±0.01, 0.11±0.01, 0.06±0.01, 0.18±0.01; and the relative protein expression levels of Sequestosome 1 (p62/SQSTM1) protein were 1.72±0.02、1.67±0.02、0.94±0.01、0.04±0.01; the relative protein expression levels of p-mTOR protein were 0.66±0.01, 0.40±0.01, 0.42±0.01, 0.04±0.01; and the relative protein expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B) protein were 0.07±0.01, 0.20±0.01, 0.87±0.05, 1.27±0.04, respectively. There were statistically significant differences between the low-, middle-, and high-dose groups and the control group (P<0.05, P<0.001).
β-ecdyssterone can regulate autophagy and promote osteogenic differentiation of BMSCs by activating the AMPK/mTOR pathway.
To observe the efficacy and safety of snake venom hemocoagulase injection combined with tranexamic acid injection and omeprazole sodium injection in the treatment of emergency patients with acute upper gastrointestinal bleeding.
Patients with acute upper gastrointestinal bleeding were divided into control group and treatment group according to the cohort method. Patients in the control group were administered with tranexamic acid injection 500 mg (iv; qd) combined with omeprazole sodium for injection 40 mg (bid); the treatment group was given snake venom hemocoagulase injection 0.5-1.5 kU (once in the morning and once in the evening) on the basis of the control group. All patients were treated for 3 d. The total effective rate, coagulation function [platelet (PLT), activated partial thromboplastin time (APTT), fibrinogen (Fib), plasma prothrombin time (PT)], hemodynamics [plasma viscosity (PV), erythrocyte sedimentation rate (ESR), whole blood high shear viscosity (WBVH) and hematocrit (HCT)], inflammatory stress response [C-reactive protein (CRP), cortisol (Cor) and neutrophil to lymphocyte ratio (NLR)], and adverse drug reactions were compared between two groups.
A total of 120 patients were enrolled in this trial, including 58 in the control group and 62 in the treatment group. After treatment, the effective rates of the control group and the treatment group were 79.31% (46 cases/58 cases) and 95.16% (59 cases / 62 cases), respectively, with statistical difference (P<0.05). After treatment, the PLT levels in the control and treatment groups were (170.18±10.86) and (180.18±9.83)×109·L-1, respectively; APTT values were (47.39±4.52) and (44.68±4.62), respectively; Fib levels were (2.98±0.33) and (3.21±0.28) g·L-1, respectively; PT values were (19.21±3.76) and (17.01±2.62) seconds, respectively; PV levels were (1.98±0.36) and (2.38±0.43) MPa·s, respectively; ESR values were (53.69±4.52)% and (59.89±14.62)%, respectively; WBVH levels were (7.08±0.23) and (7.98±0.28) MPa·s, respectively; HCT levels were (49.21±5.62) and (52.01±8.62) L·L-1, respectively; CRP levels were (8.63±1.36) and (6.38±0.93) mg·L-1, respectively; Cor values were (323.69±14.82) and (315.86±14.62) mmol·L-1, respectively; NLP levels were 4.08±0.43 and 2.98±0.48. All these differences were statistically significant (P<0.05). During the trial, the adverse drug reactions in the control group were mainly stomach distension, dizziness, headache and diarrhea, and the adverse drug reactions in the treatment group were mainly stomach distension, dizziness, headache and diarrhea. The total incidences of adverse drug reactions in the control group and the treatment group were 10.34% (6 cases / 58 cases) and 12.90% (8 cases / 62 cases), respectively, with no statistically significant difference (P>0.05).
Snake venom hemocoagulase injection combined with tranexamic acid injection and omeprazole sodium for injection has significant curative effect on emergency patients with acute upper gastrointestinal bleeding, with low adverse drug reactions.
To analyze the clinical characteristics and distribution of pathogens in adult acute empyema.
Adult patients with acute empyema were divided into the control group (patients with community-acquired empyema) and the treatment group (patients with hospital-acquired empyema) according to cohort method. The general data, clinical manifestations, laboratory examinations, imaging data, antimicrobial drugs use, invasive treatment and outcomes of the two groups were collected and compared.
There were 59 cases in the treatment group and 102 cases in the control group. Compared with the control group, the proportion of lung abscess in the treatment group was lower (1.69% vs 10.78%, P<0.05), the proportion of pneumothorax, positive rates of pus culture and mixed infection were higher (47.46% vs 18.63%, 55.93% vs 24.51%, 27.12% vs 1.96%, all P<0.05). In the control group, 27 strains of pathogens were isolated, predominantly Gram-positive cocci (74.07%), with Streptococcus anginosus group being the most common (44.44%). In the treatment group, 52 strains were isolated, predominantly Gram-negative bacilli (67.31%), with Pseudomonas aeruginosa being the most common (21.15%). Streptococcus anginosus group was sensitive to penicilins and cephalosporins, while the multidrug resistance rate of Gram-negative bacilli was high, with Pseudomonas aeruginosa showing a 69.23% resistance to meropenem. Six patients in total died, all from the treatment group and receiving non-surgical treatment, due to malignant tumors or hospital-acquired pneumonia.
In adult acute empyema, non-parapneumonic empyema is common, and there were significant differences in the pathogenic distribution between community-acquired empyema and hospital-acquired empyema.
To observe the clinical efficacy of ulinastatin injection and thymalfasin for injection in the treatment of sepsis patients and their effects on peripheral blood T lymphocyte subsets.
Sepsis patients were divided into control group and treatment group according to the cohort method. The control group was treated with ulinastatin injection in addition to initial resuscitation, hemoperfusion, and antimicrobial therapy. The treatment regimen was intravenous infusion, 2.0×105 U bid for 4 days, followed by intravenous pump infusion, 1.0×105 U bid for 6 days. The treatment group received thymalfasin for injection on base of the control group’s treatment, subcutaneous injection, 1.6 mg twice a week, for 2 weeks. The clinical efficacy, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score, peripheral blood procalcitonin (PCT), lactate (Lac), D-dimer (D-D), and levels of T lymphocyte subsets were compared between the two groups, as well as 28-day mortality rate and safety were evaluated.
A total of 43 patients were enrolled in the control group and 37 patients in the treatment group. After treatment, the total effective rates in the treatment group and the control group were 94.59% (35 cases/37 cases) and 86.05% (37 cases/43 cases), respectively, with no significant difference statistically (P>0.05). After treatment, the SOFA scores in the treatment group and the control group were (5.46±1.20) and (6.71±1.33) points; the APACHE Ⅱ scores were (16.17±3.49) and (18.63±3.82) points; the peripheral blood PCT levels were (1.51±0.33) and (1.88±0.42) μg·L-1; the Lac levels were (2.73±0.52) and (5.06±1.19) nmol·L-1; the D-D levels were (0.85±0.27) and (1.02±0.33) mg·L-1; the CD3+ levels were (38.98±4.36)% and (34.42±4.14)%; the CD4+ levels were (18.66±2.47)% and (13.17±1.96)%; the CD8+ levels were (12.35±1.42)% and (13.01±1.39)%; and the CD4+/CD8+ ratio were 1.49±0.24 and 1.04±0.22, respectively, all showing statistically significant differences (all P<0.05). The 28-day mortality rates in the treatment group and the control group were 18.92% (7 cases/37 cases) and 23.26% (10 cases/43 cases), respectively, with no significant difference statistically (P>0.05). No drug-related adverse reactions were observed in either group.
The clinical efficacy of thymalfasin for injection in the treatment of sepsis is more ideal than that of ulinastatin alone, as it can better reduce the levels of peripheral PCT, Lac, and D-D, regulate T lymphocyte subsets, demonstrating definite efficacy and safety.
To observe the anesthetic effect of esketamine injection combined with remimazolam injection in radical prostatectomy for prostate cancer.
The patients were divided into the control group and the treatment group according to cohort method. The control group was given anesthesia induction with remimazolam injection at 0.2 mg·kg-1 combined with propofol injection at 1 mg·kg-1. The treatment group was given anesthesia induction with esketamine injection at 0.5 mg·kg-1 combined with remimazolam injection at 0.1 mg·kg-1. Both groups underwent maintenance of anesthesia with propofol injection at 4-8 mg·kg-1·h-1 combined with remifentanil injection at 5-10 μg·kg-1·h-1. The analgesic effect, sedative effect, hemodynamics [before anesthesia (T0), tracheal intubation (T1), 30 min after the beginning of surgery (T2), 2 h after surgery (T3)], stress (T0~T3) and safety were compared between the two groups.
The control group and the treatment group were enrolled in 44 cases and 42 cases, respectively. At 3 h, 6 h, 12 h and 24 h after surgery, the Numerical Rating Scale (NRS) scores of the treatment groups were 2.71±0.46, 2.52±0.43, 2.24±0.32 and 2.25±0.29; the dosage of patient-controlled intravenous analgesia (PCIA) was (52.38±6.67) mL. At 3 h, 6 h, 12 h and 24 h after surgery, NRS scores of the control group were 3.49±0.52, 3.27±0.44, 2.73±0.41 and 2.54±0.39; the dosage of PCIA was (64.79±7.45) mL. For the treatment group, heart rate (HR) were (105.48±3.34), (102.67±3.45) and (100.29±1.93) beat·min-1 from T1, T2, T3; serum cortisol (Cor) levels at T1 and T2 were (257.68±29.18) and (303.75±31.52) nmoL·L-1; serum superoxide dismutase (SOD) levels at T2 and T3 were (425.85±50.45) and (422.96±50.21) U·L-1. For the control group, HR were (95.38±2.26), (91.52±2.68) and (87.15±1.40) beats·min-1 from T1, T2, T3; serum Cor levels at T1 and T2 were (307.36±32.11) and (322.38±33.45) nmoL·L-1; serum SOD levels at T2 and T3 were (401.23±46.21) and (388.24±45.87) U·L-1. The differences were statistically significant (all P<0.05). Adverse drug reactions in the treatment group mainly included emergence agitation, nausea and vomiting. Adverse drug reactions in the control group mainly included diplopia, emergence agitation, nausea and vomiting. The total incidence rates of adverse drug reactions in the treatment group and the control group were 13.64% (6 cases/44 cases) and 16.67% (7 cases /42 cases), without statistically significant difference (P>0.05).
Esketamine injection combined with remimazolam injection can achieve good anesthetic effect on patients undergoing radical prostatectomy for prostate cancer, which can effectively alleviate postoperative pain and physiological stress, and facilitate postoperative early functional recovery, with good safety.
To investigate the inhibitory effect of deoxyelephantopin on non-small cell lung cancer (NSCLC) and its potential mechanism.
Human lung adenocarcinoma H1975 cells were randomly divided into control group (routine culture), experimental-L group (1.0 μmol·L-1 deoxyelephantopin), experimental-M group (2.0 μmol·L-1 deoxyelephantopin), experimental-H group (5.20 μmol·L-1 deoxyelephantopin), Vector group (transfected Vector plasmid +5.20 μmol·L-1 deoxyelephantopin), epidermal growth factor receptor (EGFR) group (transfected with EGFR plasmid+5.20 μmol·L-1 deoxyelephantopin). 5-ethynyl-2′-deoxyuridine(EdU) assay was used to detected cell proliferation; cell apoptosis were detected by TdT mediated dUDP nick end labeling(Tunel)and flow cytometry; Western blot assay was used to detect the proteins expression; and Transwell assay was used to detect cell migration and invasion.
The proliferation rates of cells in the control group and experimental-L, -M, -H groups were (40.64±2.70)%, (29.78±3.28)%, (23.59±1.98)% and (15.72±1.01)%, respectively; the rates of TUNEL-positive cells were (4.63±0.57)%, (10.18±0.88)%, (15.96±0.79)% and (24.73±3.70)%, respectively; the relative expression levels of phosphorylated epidermal growth factor receptor (p-EGFR) protein were 0.87±0.10, 0.60±0.05, 0.49±0.04 and 0.33±0.04, respectively. Comparisons between the experimental-L, -M, -H groups and the control group, as well as comparisons among the experimental-L, -M, -H groups, revealed statistically significant differences (all P<0.05). The relative expression levels of p-EGFR/EGFR protein in the control group, experimental-H group, Vector group, and EGFR group were 0.76±0.10, 0.49±0.07, 0.47±0.05 and 0.71±0.10, respectively; apoptosis rates were (4.11±0.39)%, (26.33±2.29)%, (25.40±1.58)% and (12.68±1.73)%, respectively; the number of migrating cells was 147.78±12.69, 87.11±9.65, 93.89±9.67 and 124.00±14.10, respectively. Statistical analysis showed significant differences in the above indices between the experimental-H group and the control group, as well as between the EGFR group and the Vector group (all P<0.05).
Deoxyelephantopin can degrade EGFR, inhibit related signaling pathways, inhibit proliferation and metastasis of lung cancer cells, and induce apoptosis.
To investigate the mechanism of Dioscorea bulbifera L. against non-small cell lung cancer (NSCLC) by network pharmacology and molecular docking.
The active components and corresponding targets of Dioscorea bulbifera L. were retrieved by the traditional Chinese medicine systems pharmacology database and analysis platform. NSCLC targets were obtained and intersected. Protein-protein interaction (PPI) network analysis was performed using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of intersection targets were performed. Molecular docking techniques were used to predict the binding of core components to key targets.
Fifteen possible active components and 203 targets of active components were screened out. There were 1 653 targets for NSCLC and 120 intersection targets. The key targets were tumor antigen p53 (TP53), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor Jun (JUN), tumor necrosis factor (TNF) and interleukin-6 (IL-6) by PPI network analysis. GO and KEGG enrichment analysis showed that the key targets were mainly in transcription regulator complex, and through response to inorganic substance, played DNA-binding transcription factor binding function, and anti-NSCLC by regulating in cancer pathways. Molecular docking results showed that diosgenin and diosbulbin B were better bound to key targets.
The anti-NSCLC effect of Dioscorea bulbifera L. may be related to the regulation of cancer pathways by the action of diosgenin and diosbulbin B on TP53, AKT1, JUN, TNF and IL-6.
To investigate the effects and mechanism of wogonoside on the malignant biological behavior of pancreatic cancer SW1990 cells.
Human pancreatic cancer cells SW1990 were cultured in vitro and randomly divided into control group (normal culture), miR-NC group (transfected with miR-NC), miR-573 group (transfected with miR-573 mimics), anti-miR-NC group (transfected with miR-NC + 20 μmol·L-1 wogonoside), anti-miR-573 group (transfected with anti-miR-573 + 20 μmol·L-1 wogonoside) and experimental -L, -M, -H groups (given 5, 10 and 20 μmol·L-1 wogonoside, respectively). The ability of cell proliferation, migration and invasion were detected by methyl thiazolyl tetrazolium assay, plate cloning assay, scratch assay and Transwell assay, respectively; the expression level of microRNA (miR-573) was detected by real-time fluorescence quantitative polymerase chain reaction; Western blot were used to detect the expression levels of E-cadherin and N-cadherin protein.
The inhibition rates of experimental-H group, control group, miR-NC group, miR-573 group, anti-miR-NC group and anti-miR-573 group were (65.37±5.17)%, 0, (6.13±0.58)%, (51.94±4.99)%, (67.74±4.38)% and (28.23±2.47)%, respectively; the scratch healing rates were (27.33±2.52)%, (73.47±6.56)%, (74.27±6.86)%, (36.42±3.14)%, (25.91±2.53)% and (61.49±5.11)%, respectively; the number of invading cells were 58.05±5.46, 124.21±10.25, 126.77±11.89, 64.74±5.63, 56.65±4.79 and 103.94±10.68, respectively; the relative expression levels of miR-573 were 3.11±0.26, 1.00±0.00, 1.00±0.00, 3.96±0.37, 1.00±0.00 and 0.35±0.03, respectively; the relative expression levels of E-cadherin protein were 0.56±0.04, 0.16±0.02, 0.15±0.02, 0.50±0.04, 0.58±0.04 and 0.28±0.03, respectively; the relative expression levels of N-cadherin protein were 0.24±0.02, 0.66±0.04, 0.68±0.05, 0.31±0.03, 0.23±0.02 and 0.55±0.05, respectively. The differences of above indexes were statistically significant between the experimental -H group and the control group, between the miR-573 group and the miR-NC group, and between the anti-miR-573 group and the anti-miR-NC group (all P<0.05).
Wogonoside can decrease the proliferation, migration and invasion of pancreatic cancer cells by up-regulating the expression of miR-573, decreasing the expression of N-cadherin and increasing the expression of E-cadherin.