Latest ArticlesTo observe the analgesic effects and safety of flurbiprofen axetil injection combined with dezocine injection in postoperative patient-controlled intravenous analgesia (PCIA) for patients with intertrochanteric femoral fractures (IFF).
IFF patients were divided into control group and treatment group based on cohort method. The control group was given 0.5 mg·kg-1 dezocine injection diluted with 100 mL of 0.9% NaCl and then injected with analgesic pump. The treatment group was given 1.0 mg·kg-1 flurbiprofen axetil injection + 0.3 mg·kg-1 dezocine injection diluted with 100 mL of 0.9% NaCl and then injected with analgesic pump Postoperative visual analog scale (VAS), Ramsay sedation score (RSS), mini-mental state examination (MMSE), hemodynamic parameters (heart rate, mean arterial pressure), and safety evaluations were compared between the two groups.
A total of 67 patients were enrolled in the control group; and 53 patients were enrolled in the treatment group. Postoperative VAS scores at 2, 12 and 24 h were (1.95±0.39), (2.52±0.31) and (2.21±0.40) points in the treatment group, and (2.47±0.44), (3.17±0.34) and (2.76±0.37) points in the control group. RSS scores at the same time were (3.15±0.33), (3.39±0.35) and (3.72±0.46) points for the treatment group, and (2.79±0.54), (3.16±0.43) and (3.28±0.68) points for the control group. MMSE scores at 1, 3, and 7 days postoperatively were (25.08±2.40), (26.80±2.01) and (27.64±2.59) points in the treatment group, and (22.36±2.24), (24.53±2.25) and (25.37±1.84) points in the control group. Thirty minutes after surgery, the heart rate was (86.61±4.80) beat·min-1 in the treatment group and (82.74±4.17) beat·min-1 in the control group, while the mean arterial pressure was (74.28±4.49) mmHg and (71.76±3.42) mmHg, respectively. These indicators in the treatment group showed statistically significant differences compared to the control group (all P<0.05). The main adverse drug reactions in the treatment group were dizziness, fatigue, drowsiness, and nausea/vomiting, while the control group also had respiratory depression in addition to dizziness, fatigue, drowsiness, and nausea/vomiting. The total incidence of adverse drug reactions was 7.55% (4 cases/53 cases) in the treatment group and 20.90% (14 cases/67 cases) in the control group, with statistically significant difference (P<0.05).
Flurbiprofen axetil injection combined with dezocine injection for postoperative PCIA in IFF patients provides superior analgesic and sedative effects compared to dezocine monotherapy, enhances cognitive function, stabilizes hemodynamics, and has good safety.
To investigate the effect of arctigenin on bronchial epithelial cell injury caused by Pseudomonas aeruginosa (PA) infection and its mechanism.
BEAS-2B cells were randomly divided into control group (conventional culture), PA group (1.50×108 CFU·mL-1 PA infection), PA+ low dose group (PA combined with 10.00 mmol·L-1 burdock aglycone), PA+ high-dose group (PA combined with 20.00 mmol·L-1 burdock aglycone). The expression of inflammatory factors and glutathione (GSH) was detected by kit assay, glutathione peroxidase 4 (GPX4) protein was detected by Western blot assay, and lipid peroxidation levels were detected by immunofluorescence assay.
The IL-6 contents of control group, PA group, PA+ low dose group and PA+ high dose group were (20.43±2.82), (106.28±8.07), (76.66±5.73) and (50.57±3.98) pg·mL-1, respectively; the GSH contents were (25.95±1.46), (10.59±0.60), (13.98±0.74) and (21.52±2.36) ng·mL-1, respectively; GPX4 protein expression levels were 0.76±0.06, 0.33±0.05, 0.46±0.05 and 0.62±0.06, respectively; the lipid peroxidation levels were (100.00±4.29)%, (470.91±36.33)%, (331.16±27.04)% and (160.16±18.65)%, respectively. The above indexes in PA group compared with control group, PA+ low dose group and PA+ high dose group were compared with PA group, and the differences were all statistically significant (all P<0.01).
Arctigenin can reduce the inflammation of PA-infected BEAS-2B cells by inhibiting GPX4-related ferroptosis pathway.
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 observe the clinical efficacy and safety of different doses of atorvastatin calcium tablets combined with trimetazidine hydrochloride tablets in the treatment of patients with chronic heart failure (CHF).
CHF patients were randomly assigned to low-dose group, high-dose group and control group using a digital randomization method. The control group received conventional heart failure treatment in addition to trimetazidine hydrochloride tablets (20 mg per dose, tid). The low-dose group received conventional atorvastatin calcium tablets (20 mg per dose, qd) on basis of the treatment given to the control group. The high-dose group received higher dose of atorvastatin calcium tablets (40 mg per dose, qd) in addition to the treatment for the control group. All treatment continued for 3 months. The clinical efficacy, heart function indicators, three-dimensional myocardial fibrosis parameters, myocardial cell apoptosis-related factors and safety were compared among the three groups.
A total of 8 cases were dropped during the trial, and 30 cases were included in the low-dose group, 24 cases in the high-dose group, and 26 cases in the control group. After treatment, the efficacy rates were 76.67% (23 cases/30 cases) for the low-dose group, 91.67% (22 cases/24 cases) for the high-dose group, and 61.54% (16 cases/26 cases) for the control group. The difference between the high-dose group and the control group was statistically significant (P<0.05). After treatment, the left ventricular ejection fractions for the low-dose group, high-dose group and control group were (52.25±2.11)%, (55.34±2.76)% and (48.72±2.48)%, respectively; the left ventricular end-diastolic diameters were (51.33±3.94), (48.63±4.79) and (55.79±4.85) mm, respectively; the left ventricular end-systolic diameters were (39.77±3.53), (36.72±3.29) and (42.78±3.69) mm, respectively; troponin Ⅰ levels were (1.62±0.33), (1.36±0.29) and (1.84±0.36) ng·L-1, respectively; N-terminal pro B-type natriuretic peptide levels were (797.25±79.32), (749.20±84.65) and (854.15±90.57) pg·mL-1, respectively; global strain values were -29.87±5.19, -32.96±5.82 and -26.33±5.46, respectively; cell membrane receptor protein levels were (2.55±0.46), (2.30±0.36) and (2.84±0.50) μg·L-1, respectively; soluble Fas ligand levels were (0.23±0.06), (0.19±0.04) and (0.28±0.09) μg·L-1, respectively; the differences among the three groups and between each pair of groups for the above indicators were statistically significant (P<0.05, P<0.01, P<0.001). The main adverse drug reactions in the low-dose group were gastrointestinal bloating and constipation, while the high-dose group primarily experienced constipation. The control group mainly reported nausea. The incidences of adverse drug reactions in the low-dose, high-dose and control groups were 6.67%, 4.17% and 3.85%, respectively, without statistically significant differences (all P>0.05).
The curative effect of intensive dose atorvastain calcium tablets combined with trimetazidine hydrochloride tablets in the treatment of CHF is better than that of conventional dose atorvastatin combined with trimetazidine hydrochloride tablets, and the safety is good.
To observe the clinical efficacy and safety of general anesthesia induction with different doses of remimazolam in the vascular interventional treatment of intracranial aneurysms, and observe the safety.
The patients with intracranial aneurysms who will receive vascular interventional treatment for intracranial aneurysms were divided into low-dose group (0.2 mg·kg-1 remimazolam), middle-dose group (0.3 mg·kg-1 remimazolam) and high-dose group (0.4 mg·kg-1 remimazolam) according to cohoert. The three groups completed intravenous injection of 0.2-0.4 mg·kg-1 remimazolam. When the consciousness of patients disappeared, 10 μg·kg-1 alfentanil and 0.2 mg·kg-1 cisatracurium besilate were used for anesthesia induction, and 0.3-1.0 mg·kg-1·h-1 remimazolam+ 0.1 μg·kg-1·min-1 remifentanil + 0.2 mg·kg-1·h-1 cisatracurium besilate were applied for anesthesia maintenance. The anesthetic effect, heart rate (HR) and mean arterial pressure (MAP) during recovery period, oxidative stress indexes at different time points and, remimazolam remedy were compared among the three groups, and the safety was evaluated.
There were 27 cases in low-dose group, 28 cases in middle-dose group and 25 cases in high-dose group. The HR values at extubation in low-dose group, middle-dose group and high-dose group were (79.47±6.85), (75.84±6.71) and (72.03±5.79) beat·min-1, HR values at 5 min after extubation were (81.92±6.59), (78.09±7.03) and (74.17±7.26) beat·min-1, serum superoxide dismutase (SOD) levels at 24 h after surgery were (87.61±11.25), (95.49±14.02) and (103.86±15.37) U·mL-1, serum malondialdehyde (MDA) levels were (19.69±2.74), (17.24±2.45) and (15.08±2.29) mmol·L-1, serum catalase (CAT) levels were (66.75±8.39), (71.69±8.55) and (76.91±9.13) U·mL-1, the onset time of sedation was (94.36±4.42), (82.29±4.15) and (75.17±5.38) s, respectively, and there were significant differences between any two groups of the three groups (all P<0.05). There were 4 cases (14.81%), 0 case and 0 case of remimazolam remedy in low-dose group, middle-dose group and high-dose group, respectively, and the index in middle-dose group and high-dose group was significantly different compared with that in low-dose group (P<0.05). In the low-dose group, there was 1 case (3.70%) of hypotension, 1 case (3.70%) of respiratory depression, and 2 cases (7.41%) of intraoperative body movement. In the middle-dose group, there was 1 case (3.70%) of hypotension, 1 case (3.57%) of bradycardia, and 1 case (3.70%) of respiratory depression. In the high-dose group, there was 1 case (4.00%) of hypotension, 2 cases (8.00%) of bradycardia, and 2 cases (8.00%) of respiratory depression. There was no statistically significant difference in the incidence of adverse drug reactions among the three groups (all P>0.05).
The induction of general anesthesia with different doses of remimazolam has a certain application effect in the vascular interventional treatment of intracranial aneurysms, and the induction of general anesthesia with high doses of remimazolam (0.4 mg·kg-1) is the most ideal. It is not only beneficial to maintaining the stability of hemodynamics during the recovery period, and alleviating the oxidative stress response, but also shortening the onset time of sedation, reduce the number of remedial cases, and it has good safety.
To establish a quantitative analysis method for serum vitamin D (VD) based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and evaluate its clinical application value in pediatric nutritional support.
Serum samples were processed with acetonitrile, using 25-hydroxyvitamin D2-d6 (25-OH-VD2-d6) and 25-hydroxyvitamin D3-d6 (25-OH-VD3-d6) as internal standards. The chromatographic column was Kinetex C18 (50.0 mm × 3.0 mm, 2.6 μm). The mobile phase consisted of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution, with gradient elution at a flow rate of 0.5 mL·min-1 and an injection volume of 10 μL. The column temperature was set to 30 ℃. Electrospray ionization was used in positive ion mode, with multiple reaction monitoring. The LC-MS/MS method was evaluated for specificity, calibration curves, lower limits of quantification, precision, recovery rate, stability, and matrix effects. The method was applied to detect VD levels in the serum of infants from the external group (oral 10 μg·kg-1 VD drops, qd) and the parenteral group [parenteral nutrition solution with injectable fat-soluble vitamin (Ⅰ) administered intravenously, it was equivalent to 10 μg·mL-1 VD, qd].
Both 25-OH-VD2 and 25-OH-VD3 showed good linearity in the range of 5-100 ng·mL-1, with the 25-OH-VD2 standard curve of y=1.00x+2.34×10-2 (R=0.999 8), and a lower limit of quantification (LLOQ) of 0.5 ng·mL-1; 25-OH-VD3 standard curve of y=1.00x+5.6×10-3 (R=0.999 8), and LLOQ of 1 ng·mL-1. The recovery rate of 25-OH-VD2 quality control samples was 95.59%-105.38%, with intra- and inter-day precision ≤ 4.75% and ≤ 4.68%, respectively. The recovery rate of 25-OH-VD3 was 98.38%-113.63%, with intra- and inter-batch precision ≤5.64% and ≤7.83%, respectively. Stability of 25-OH-VD2 and 25-OH-VD3 samples at different concentrations was good under various conditions, with matrix effects ranging from 85%-110% and 88%-112%, respectively. After enteral or parenteral VD supplementation, the serum levels of 25-OH-VD2 and 25-OH-VD3 in both groups of preterm infants significantly increased, with the parenteral group showing significantly higher concentrations of 25-OH-VD2 and 25-OH-VD3 compared to the enteral group (P<0.05). The daily weight gain rate of preterm infants in the parenteral group was also significantly higher than those in the enteral group (all P<0.05).
The quantitative analysis method of serum VD based on LC-MS/MS has strong specificity and high sensitivity, which is suitable for the monitoring of VD level in premature infants.
To explore the design and application of digital intelligence quality control technology in drug clinical trials, aiming to improve the quality and efficiency of these trials.
Based on the characteristics and requirements of quality control in drug clinical trials, a digital intelligence quality control model was designed and applied throughout the entire process of drug clinical trials. The system’s performance and security were evaluated.
The digital intelligence quality management system can significantly enhance the accuracy and completeness of clinical trial data, improve the efficiency of drug clinical trials, and strengthen real-time monitoring capabilities to ensure compliance and safety of the trials.
The digital intelligence quality management system can optimize resource allocation, shorten trial duration, and reduce overall costs. It provides new perspectives and methodologies for quality control in drug clinical trials, laying a reliable foundation for the digital transformation of the biopharmaceutical industry.
To investigate the effect of anemoside B4 on the malignant biological behavior of non-small cell lung cancer (NSCLC) cells mediated by microRNA-142-3p (miR-142-3p) on the expression of high mobility group protein A1 (HMGA1).
A549 cells were divided into A549 group (normal culture), anemoside B4 group (100 μg·mL-1 anemoside B4 treatment), inhibitor NC group (100 μg·mL-1 anemoside B4+ transfection inhibitor NC treatment), miR-142-3p inhibitor group (100 μg·mL-1 anemoside B4+ transfected with miR-142-3p inhibitor treatment), si-NC group (100 μg·mL-1 anemoside B4+ co-transfected with miR-142-3p inhibitor and si-NC treatment), si-HMGA1 group (100 μg·mL-1 anemoside B4+ co-transfected with miR-142-3p inhibitor and si-HMGA1 treatment). Real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB) were used to detect the expression of miR-142-3p and HMGA1. Cell proliferation, migration and apoptosis were detected by 5-acetylidene-2′-deoxyuracil riboside (Edu), Transwell and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL).
The miR-142-3p relative expression levels of A549 group, anemoside B4 group, inhibitor NC group and miR-142-3p inhibitor group were 1.00±0.14, 1.58±0.18, 1.60±0.21 and 1.12±0.16, respectively; the relative expression levels of HMGA1 protein were 1.00±0.23, 0.56±0.07, 0.59±0.08 and 0.95±0.21, respectively; the proliferation rates were (84.62±9.11)%, (62.15±7.20)%, (63.89±7.77)% and (76.35±8.11)%, respectively; the migration number was (156.23±17.54), (80.65±8.67), (82.15±8.96) and (111.55±12.75) cells, respectively; the apoptosis rates were (8.96±0.95)%, (32.56±3.56)%, (33.95±3.79)% and (16.89±1.92)%, respectively. The proliferation rates of si-NC group and si-HMGA1 group were (75.98±8.05)% and (64.52±7.25)%, respectively; the migration number was (118.85±12.98) and (86.95±9.21) cells, and the apoptosis rates were (17.58±2.02)% and (28.15±3.13)%, respectively. The above indexes in A549 group were compared with anemoside B4 group, miR-142-3p inhibitor group were compared with inhibitor NC group, si-HMGA1 group were compared with si-NC group, the differences were all with statistically significant (all P<0.05).
Anemoside B4 may inhibit proliferation and migration of NSCLC cells and promote apoptosis by regulating the miR-142-3p/HMGA1 axis.
Endocrine therapy is the main treatment mode for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer, but primary or secondary endocrine resistance can lead to treatment failure and affect patient survival. Studies have shown that abnormalities in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (PAM pathway) account for more than 50% of endocrine-resistant patients. The PAM pathway is not only the main mechanism of endocrine therapy resistance in breast cancer, but also mediates resistance to chemotherapy and targeted therapy. AKT is one of the core kinases of the PAM pathway, and inhibiting its activity can inhibit the aberrant activation of the pathway. Capivasertib is the first AKT kinase inhibitor, and in the phase Ⅲ CAPItello-291 clinical study, compared with fulvestrant alone, the combination of capivasertib and fulvestrant significantly increased PFS in the overall population and the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/protein kinase B/phosphatase and tensin homolog (PIK3CA/AKT/PTEN)mutant population. In addition, capivasertib has a good safety profile, and the common adverse reactions are elevated blood glucose, diarrhea, and skin adverse reactions, which are mostly grade 1-2 and can be well tolerated. Breast cancer treatment guidelines all recommend it for post-line selection in people with PIK3CA/AKT/PTEN mutations who have failed endocrine therapy. This article mainly introduces the pharmacological mechanism, pharmacodynamics, pharmacokinetics, clinical trials and safety information of capivasertib, in order to facilitate the clinical application of the drug.
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.