ArchiveTo observe the clinical efficacy and safety of dexmedetomidine injection combined with remifentanil injection and scalp nerve block in patients undergoing craniotomy for aneurysm clipping.
Patients who underwent craniotomy for aneurysm clipping were divided into control group and treatment group according to random number method . All patients were treated with a unified scheme for anesthesia induction, and ultrasound-guided scalp nerve block was performed after induction. During the anesthesia maintenance phase, remifentanil injection (0.1-0.2 μg·kg-1·min-1), atracurium besylate injection (0.2 mg·kg-1·h-1) and propofol emulsion injection (3-8 mg·kg-1·h-1) were continuously pumped into the two groups. And dexmedetomidine injection (0.4 μg·kg-1·min-1) was pumped into the treatment group on the basis of control group. The recovery time, extubation time, hemodynamic changes, analgesia and sedation scores, brain injury and emergency response related markers were compared between the two groups, and the safety was evaluated.
A total of 110 cases were enrolled, including 55 in control group and 55 in treatment group. The recovery time of control group and treatment group were (19.73±3.52) and (17.87±2.69) min, respectively; and the extubation time were (21.78±3.83) and (19.33±3.46) min, respectively; the mean arterial pressure (MAP) at 5 minutes after intubation (T1) were (83.67±12.99) and (89.31±14.39) mmHg, respectively; and at nerve block (T2), the MAP were (81.40±13.92) and (86.58±12.18) mmHg, respectively; at 10 minutes after the operation (T5), the MAP were (83.56±12.58) and (89.02±13.48) mmHg, respectively; and the heart rate (HR) at T1 were (65.55±11.39) and (72.42±11.66) beats·min-1, respectively; the HR at T2 were (63.65±13.54) and (70.15±12.29) beats·min-1, respectively; at 10 minutes after nerve block (T3), the HR were (64.65±14.26) and (71.13±12.49) beats·min-1, respectively; when sawing the skull (T4), the HR were (62.44±12.67) and (69.02±13.57) beats·min-1, respectively; and at T5, the HR were (67.18±10.40) and (74.84±13.77) beats·min-1, respectively. Compared with control group, the differences of the above indicators of treatment group were all statistically significant (all P<0.05). The total incidence of adverse drug reaction rates in control group and treatment group were 30.91% (17 cases /55 cases) and 14.55% (8 cases /55 cases), respectively, with statistically significant difference (P<0.05).
Dexmedetomidine injection combined with remifentanil injection and scalp nerve block has good clinical efficacy and safety in craniotomy and aneurysm clipping.
To observe the clinical efficacy and safety of subanesthetic dose of esketamine injection and quadratus lumborum block in elderly patients undergoing radical resection of colorectal cancer.
Patients undergoing radical resection of colorectal cancer were divided into treatment group and control group according to the anesthesia method. Both groups underwent bilateral quadratus lumborum block under ultrasound guidance. Anesthesia induction was performed with etomidate injection at a dose of 0.1-0.3 mg·kg-1, sufentanil injection at a dose of 0.3-0.6 μg·kg-1, midazolam injection at a dose of 0.04-0.06 mg·kg-1, and cisatracurium injection at a dose of 0.2 mg·kg-1. Anesthesia was maintained with propofol injectation emulasion 4-8 mg·kg-1·h-1, remifentanil for injection 0.15-0.3 μg·kg-1·min-1, and dexmedetomidine injection 0.2-1.0 μg·kg-1·h-1. The treatment group received a single intravenous injection of 0.25 mg·kg-1 esketamine injection 5 min before surgery, while the control group received routine anesthesia management without esketamine injection intervention. Both groups received intravenous patient-controlled analgesia postoperatively. Hemodynamics, analgesia and sedation, postoperative opioid consumption, and recovery quality were compared between the two groups, and safety was evaluated.
A total of 108 patients were enrolled, the treatment group included 52 cases and the control group included 56 cases. The mean arterial pressure (MAP) at T3 in the treatment and control groups were (86.04±6.43) and (83.20±6.80) mmHg, respectively; the heart rate (HR) at T3 were (76.21±5.56) and (73.96±5.31) beats·min-1, respectively; the numerical rating scale (NRS) at 12 h postoperatively were (2.04±0.77) and (2.29±0.65) points, respectively; sufentanil consumption were (88.63±11.28) and (94.30±12.22) μg, respectively; the effective pressing times of the analgesia pump within 24 h postoperatively were (5.65±1.17) and (6.23±1.40) times, respectively, and the effective pressing times of the analgesia pump within 24-48 h postoperatively were (7.06±1.51) and (7.89±2.18) times, respectively; the awakening time were (21.25±4.58) and (23.68±4.87) min, respectively, and the length of stay in the postanesthesia care unit (PACU) were (36.23±6.91) and (40.05±7.42) min, respectively. The differences were all statistically significant (P<0.05, P<0.01). The adverse drug reactions in the treatment group were dizziness, nausea and vomiting, while the adverse drug reaction in the control group was skin pruritus. The total incidence of adverse reactions in the treatment and control groups was 3.85% (2 cases/52 cases) and 1.79% (1 case/56 cases), respectively, and the difference was not statistically significant (P>0.05).
The application of subanesthetic dose of esketamine and quadratus lumborum block in elderly patients undergoing radical resection of colorectal cancer can effectively reduce postoperative opioid consumption, provide good sedation and analgesia, maintain hemodynamic stability, protect lung function, and improve recovery quality. It has little impact on cognitive function and sleep quality, and has good safety.
To observe the clinical efficacy and safety of duloxetine hydrochloride enteric-coated capsules combined with Bifidobacterium quadruple live bacteria tablets in patients with depression accompanied by gastrointestinal disorders.
According to the treatment method, patients with depression and gastrointestinal dysfunction were divided into control group and treatment group. The control group took 30 mg duloxetine hydrochloride enteric-coated capsules once a day after breakfast, and adjusted to 60 mg once a day after 1 week. The treatment group was combined with 1.5 g Bifidobacterium quadruple viable tablets, 3 times a day. Both groups were treated for 8 weeks. The clinical therapeutic effects, and intestinal microbiota composition of the two groups of patients were compared, and safety evaluation was conducted.
A total of 76 patients were enrolled, 32 patients were included in the control group and 44 patients in the treatment group. After treatment, the total effective rate of the treatment group was 84.09% (37 cases /44 cases), and that of control group was 62.50% (20 cases/32 cases), and the difference was statistically significant (P<0.05). After treatment, the Lactobacillus of treatment group and control group were (7.14±1.14) and (6.54±1.24) lg CFU·g-1, respectively; Staphylococcus were (3.73±0.73) and (4.12±0.74) lg CFU·g-1, respectively; Bifidobacterium were (8.39±1.44) and (7.69±1.34) lg CFU·g-1, respectively; Escherichia coli were (7.08±0.93) and (7.52±0.81) lg CFU·g-1, respectively; Enterococcus faecalis were (5.95±0.76) and (6.50±0.84) lg CFU·g-1, respectively. The above indicators of treatment group were compared with those of the control group, and the differences were statistically significant (all P<0.05). The adverse drug reactions in the treatment group mainly included nausea, dry mouth, constipation, insomnia and dizziness. The adverse drug reactions in the control group mainly included palpitations, nausea, dry mouth, constipation, insomnia and dizziness. The total incidence of adverse drug reactions in the treatment group and the control group were 15.91% (7 cases /44 cases) and 40.63% (13 cases /32 cases), respectively, with no statistically significant different (P<0.05).
Duloxetine hydrochloride enteric-coated capsules combined with Bifidobacterium quadruflora live bacteria tablets have a good clinical efficacy in patients with depression accompanied by gastrointestinal disorders. They can improve the intestinal flora of patients and reduce the occurrence of adverse drug reactions.
To observe the clinical efficacy and safety of emedastine difumarate sustained-release capsules in conjunction with tacrolimus ointment for treating elderly patients with skin pruritus.
The senile patients with pruritus who were treated in our hospital were divided into control group and treatment group according to the treatment methods. The control group was treated with tacrolimus ointment twice a day on the basis of conventional treatment for 6 consecutive weeks. The treatment group, on the basis of the control group, orally administered 2 mg of emestine fumarate sustained-release capsules after breakfast or before going to bed, twice a day for 6 consecutive weeks. The clinical efficacy of patients, evaluation of itching degree, the levels of eosinophils (EOS), histamine and immunoglobulin E (IgE), levels of inflammatory response indicators recurrence situation, and safety were compared between two groups.
A total of 122 cases were included in this study, including 59 cases in the control group and 63 cases in the treatmnet group. The total effective rates of treatment in the treatmnet group and the control group were 92.06% (58 cases/63 cases) and 76.27% (45 cases/59 cases), respectively; the pruritus degree scores were (2.35±0.48) and (2.64±0.52) points, respectively; the EOS were (208.07±33.69) and (225.61±34.82) ×106·L-1 respectively; the histamine was (0.79±0.13) and (1.25±0.21) ng·mL-1, respectively; the IgE was (42.07±6.56) and (45.17±6.08) ng·mL-1, respectively; the monocyte chemoattractant protein-1 was (279.77±39.14) and (298.52±47.64) pg·mL-1, respectively; the eosinophil chemoattractant was (44.77±6.21) and (47.96±7.45) pg·mL-1, respectively; the interleukin-6 was (6.56±1.07) and (7.13±1.08) pg·mL-1, respectively; the tumor necrosis factor -α was (5.91±0.69) and (6.24±0.89) pg·mL-1, respectively, and the recurrence rates were 11.11% and 25.42%, respectively. The comparison of above indicators showed that there were statistically significant differences between the two groups (P<0.05, P<0.01, P<0.001). The adverse reactions in the control group included a burning sensation on the skin and rosacea, while those in the treatmnet group included a burning sensation on the skin, rosacea, drowsiness, headache, dizziness and tinnitus. The adverse reaction rates of the control group and the treatmnet group were 11.86% and 19.05%, without tatistically significant difference (P>0.05).
Emedastine difumarate sustained-release capsules combined with tacrolimus ointment can alleviate patients′ pruritus symptoms, reduce inflammatory response, regulate immune function, improve efficacy and reduce the risk of recurrence without increasing adverse reactions.
To understand the distribution and antibiotic resistance changes of clinical isolated Klebsiella pneumoniae in Xinjiang from 2019 to 2023, and provide a basis for the rational use of antibiotics in clinical practice.
Clinical isolates from Xinjiang region between 2019 and 2023 were collectd and identified and subjected to drug sensitivity tests using the fully automated bacterial identification analyzer VITEK-2 compact and VITEK-MS, supplemented by the K-B paper method.
Over the course of 5 years, a total of 72 678 strains of Klebsiella pneumoniae were detected, among which 19 061 were extended-spectrum β-lactamases (ESBLs) producing strains, accounting for a detection rate of 26.23%. The strains mainly come from sputum, urine, blood, etc. The top three departments in terms of strain distribution were the intensive care medicine, respiratory medicine, and pediatrics. The resistance rates of Klebsiella pneumoniae to third-generation cephalosporins ceftriaxone and ceftazidime were 21.42% and 15.73%, respectively. The resistance rates to carbapenems ranged from 6.82% to 7.48%, and the resistance rate to amikacin was 4.15%.
Klebsiella pneumoniae has become one of the most common pathogenic bacteria in clinical practice. The resistance of Klebsiella pneumoniae detected in Xinjiang is not optimistic. In order to improve the treatment effect of antibiotics, the resistance of antibiotics in the local area should be continuously monitored, and antibiotics should be selected reasonably based on drug sensitivity results.
To evaluate the in vitro antibacterial effects and post-antibiotic effect (PAE) of dequalinium chloride against common pathogens isolated from oral infections in China in recent years.
The minimum inhibitory concentration (MIC) was determined by the standard microbroth or agar (for anaerobes) two-fold dilution method; the minimum bactericidal concentration (MBC) was determined by the broth two-fold dilution method; time-kill curves and PAE were determined by the colony count method.
MICs of dequalinium chloride and commonly used antimicrobial drugs were determined for 274 bacterial strains from 22 hospitals in 19 cities across China. Result showed that, for Gram-positive bacteria, the MIC50 values of dequalinium chloride against Staphylococcus aureus and Streptococcus pyogenes were 1 and 2 mg·L-1, respectively, with MIC90 values of 2 and 4 mg·L-1, respectively. For Streptococcus pneumoniae, Enterococcus faecalis, and the viridans group streptococci, the MIC50 values were 8, 4 and 8 mg·L-1, respectively, while the MIC90 values were 8, and 16 mg·L-1, respectively. Among Gram-negative bacteria, the MIC50 and MIC90 values of dequalinium chloride against Klebsiella pneumoniae were both 64 mg·L-1; and >512 mg·L-1 for MIC50 against Pseudomonas aeruginosa. For 32 strains of anaerobic bacteria, the MIC50 and MIC90 of dequalinium chloride were 16 and 128 mg·L-1, respectively. Dequalinium chloride showed superior antibacterial activity against genera of Peptostreptococcus and Porphyromonas compared to Prevotella. MBC and time-kill curves showed that dequalinium chloride has a good bactericidal effect on Staphylococcus aureus, Streptococcus pyogenes, and oral streptococci, killing bacteria from an initial count of 1.0×105-1.0×106 CFU·mL-1 to 0 at 1-4 times MIC concentration within 4-24 h. It also showed good bactericidal effect on Enterococcus faecalis. The time-kill curves indicating a concentration-dependent characteristic of the drug. The PAE of dequalinium chloride against the above four bacterial strains was between 0.5-1 h.
Dequalinium chloride exhibits superior antibacterial activity against Gram-positive bacteria than Gram-negative bacteria and anaerobes, especially against Staphylococcus aureus and Streptococcus pyogenes, warranting further clinical research.
To evaluate in vitro activity of ceftobiprole against clinical isolated bacteria in recent years in China.
The minimal inhibitory concentrations (MICs) were determined by the microbroth dilution method.
A total of 948 clinical isolates collected from nationwide between 2019 to 2020 were studied. Ceftobiprole exhibited excellent antibacterial activity against gram-positive cocci, the value of MIC90 was 0.5 mg·L-1 for methicillin susceptible Staphylococcus spp and susceptibility rates of methicillin resistant Staphylococcus aureus (MRSA) were 93.1%, which was better than that of ceftaroline (72.3%). The MIC values of ceftobiprole against penicillin nonsusceptible Streptococcus pneumoniae (PNSSP) ranged from 0.06 to 1 mg·L-1, with 80.0% susceptibility rate . The values of MIC90 of ceftobiprole were ≤2 mg·L-1 for other streptococci and Enterococcus faecalis. Against Gram-negative bacteria, ceftobiprole also showed better antibacterial activity against non-extended spectrum β-lactamases (ESBLs) Escherichia coli, non-ESBLs Klebsiella pneumoniae, ampicillin-susceptible Haemophilus influenzae and Moraxella catarrhalis, the values of MIC90 ≤0.5 mg·L-1 and susceptible strains more than 98.1%. The activity of ceftobiprole against Pseudomonas aeruginosa was similar to that of ceftazidime and cefepime.
Ceftobiprole showed excellent antibacterial activity against clinical isolates, include MRSA, PNSSP, and Haemophilus influenzae in recent years in China, which similar to the surveillance results in Europe and America. The clinical prospect is worthy of expectation.
To discuss the effects of acacetin on lung injury in Mycoplasma pneumoniae pneumonia (MPP) mice and analyze the relationship between its mechanism and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
A MPP mouse model was constructed, and successfully modeled mice were stochastically divided into model group, low, medium and high dose acacetin experimental groups (acacetin-L, M, and H groups: 12.5, 25.0, and 50.0 mg·kg-1 acacetin) and high-dose acacetin-H+JAK2 activator coumarin group (acacetin-H+coumarin 50 mg·kg-1 acacetin-L and 2 mg·kg-1 coumarin), each with 12 mice. Twelve normal healthy mice were intranasally instilled with an equal amount of physiological saline as the control group. Blood gas analyzer was used to detect arterial partial pressure of carbon dioxide (PaCO2) and arterial partial pressure of oxygen (PaO2) of mice, oxygen concentration analyzer was used to detect fraction of inspired oxygen (FiO2), and the oxygenation index (OI) was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory factors. Biochemical method was used to detect oxidative stress indicators. The lung index and lung wet dry ratio were weighed and calculated. Hematoxylin-eosin (HE) staining was employed to evaluate the pathological lesions in lung tissue. Western blot assay was performed to detect the protein expression of JAK2/STAT3 signaling pathway-related molecules.
The OI value of the acacetin-L, -M, -H groups, control group, model group, and acacetin-H+coumamycin group were (274.63±30.02), (320.16±35.79), (374.55±39.88), (403.57±43.61), (220.31±26.78) and (241.03±29.14)mmHg, respectively; the IL-6 levels were (124.56±13.27), (87.61±9.23), (56.34±6.77), (36.50±4.15), (172.59±18.24) and (149.33±16.05)pg·mL-1, respectively; the MDA contents were (4.06±0.45), (2.97±0.31), (1.93±0.22), (1.82±0.20), (5.31±0.58) and (4.69±0.49) nmol·mL-1, respectively; the lung index was 1.31±0.15, 0.99±0.11, 0.57±0.07, 0.52±0.06, 1.78±0.19, and 1.54±0.17, respectively; the lung wet/dry weight ratio was (6.83±0.73)%, (5.61±0.58)%, (4.35±0.49)%, (4.10±0.45)%, (7.86±0.86)% and (7.33±0.81)%, respectively; the phosphorylated(p)-JAK2/JAK2 ratio were 0.71±0.08, 0.56±0.06, 0.43±0.05, 0.39±0.04, 0.86±0.09 and 0.79±0.08, respectively; the p-STAT3/STAT3 ratio were 0.67±0.07, 0.46±0.06, 0.30±0.04, 0.16±0.02, 0.83±0.09 and 0.74±0.08, respectively. There were statistically significant differences in the above indicators between the model group and the control group, between the acacetin-H group and the model group, and between the acacetin-H+coumarin group and the acacetin-H group (all P<0.05).
Acacetin can effectively improve lung injury in MPP mice, possibly by inhibiting the JAK2/STAT3 signaling pathway.
To discuss the effects of esculetin on myocardial ischemia-reperfusion injury in rats by regulating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
A total of 60 rats were randomly divided into control group, model group, low-dose (L)-esculetin (20 mg·kg-1) experimental group, high-dose (H)-esculetin (40 mg·kg-1) experimental group, and H-esculetin+inhibitor (40 mg·kg-1 esculetin and 20 mg·kg-1 JAK2/STAT3 inhibitor WP1066) group, with 12 rats in each group. Except for the control group, rats in all other groups were subjected to myocardial ischemia-reperfusion modeling. Triphenyltetrazolium chloride (TTC) staining was used to evaluate infarct size; hematoxylin-eosin staining (HE) staining was used to observe histopathological changes; TdT-mediated dUTP Nick-End Labeling (TUNEL) staining was used to observe myocardial apoptosis; enzyme linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines; Western blot was used to detect protein expression of JAK2/STAT3 pathway in rat myocardium.
The cardiomyocytes of the rats in the model group were enlarged and arranged in a disorderly manner, while the myocardial damage of rats in the L-esculetin group and the H-esculetin experimental group was reduced. The myocardial infarction areas of the rats in the control group, model group, L-esculetin experimental group, H-esculetin experimental group and H-esculetin+inhibitor group were (3.24±0.35)%, (31.36±3.51)%, (20.75±2.37)%, (10.48±1.16)% and (29.56±3.27)%, respectively; the cardiomyocyte apoptosis rates were (6.37±0.75)%, (56.24±6.03)%, (38.72±3.94)%, (21.46±2.37)% and (51.05±5.28)%, respectively, the levels of interleukin-1β (IL-1β) were (9.34±1.02), (158.95±16.83), (125.49±13.26), (94.83±10.54) and (151.27±16.42) pg·mL-1, respectively; the levels of interleukin-18 (IL-18) were (13.27±1.46), (568.93±59.95), (486.38±51.32), (312.63±33.41) and (527.46±56.25) pg·mL-1, respectively; the levels of tumor necrosis factor-α (TNF-α) were (7.85±0.98), (124.84±14.64), (88.95±9.63), (53.58±5.97) and (116.32±13.27) pg·mL-1, respectively; the relative expression levels of pentraxin 3 (PTX3) protein were 0.86±0.11, 0.32±0.04, 0.53±0.07, 0.71±0.08 and 0.69±0.08, respectively; the relative expression levels of phospho-JAK2 (p-JAK2) protein were 0.81±0.09, 0.36±0.05, 0.54±0.07, 0.73±0.08 and 0.39±0.05, respectively; the relative expression levels of phospho-STAT3 (p-STAT3) protein were 0.78±0.09, 0.29±0.04, 0.52±0.06, 0.74± 0.09 and 0.33±0.04, respectively. Comparing the control group with the model group, the model group with the L-phenithin experimental group, the L-phenithin group with the H-phenithin experimenal group, and the H-phenithin experimental group with the H-phenithin+inhibitor group, there were statistically significant differences in the above indicators (all P<0.05).
Esculetin alleviates myocardial ischemia-reperfusion injury in rats by activating the JAK2/STAT3 signaling pathway.
This article aimed to explore the targets of the innovative drug HSK31679 in treating metabolic dysfunction-associated steatohepatitis (MASH), and to validate the changes in drug efficacy before and after target knockout through in vivo experiments.
Using the drug and disease databases, HSK31679 and MASH related targets were identified. The core targets were further determined by Cytoscape software. Auto Dock predicted the binding affinity of corresponding proteins to HSK31679. MASH mouse models of wild-type and liver caspase 8 (CASP8) knockout were constructed. Mice were divided into control group (normal feeding of mice + 0.5 mL saline administration), model group (modeling of mice + 0.5 mL saline administration), experimental group (modeling of mice + 3 mg·kg-1 HSK31679 administration), ΔCASP8 model group (modeling of CASP8 knockout mice + 0.5 mL saline administration) and ΔCASP8 experimental group (modeling of CASP8 knockout mice + 3 mg·kg-1 HSK31679 administration), with 8 mice in each group. Serum biochemical indicators were measured using an enzyme-linked immunosorbent assay (ELISA) after treatment, and liver sections were stained with HE to velidate the role of core targets of HSK31679′s treatment of MASH.
HE staining revealed significant and typical MASH-associated cellular damage in hepatocytes of the model group, indicating successful model establishment. Five major core targets associated with both HSK31679 and MASH were identified, and HSK31679 exhibited favorable binding activity with the CASP8 protein among them. In animal experiments, the serum triglyceride (TG) levels in the blank group, model group, experimental group, ΔCASP8 model group, and ΔCASP8 experimental group were (0.61±0.05), (1.01±0.15), (0.66±0.13), (0.62±0.09), and (0.63±0.12) mmol·L-1, respectively; the total cholesterol (TC) levels were (1.24±0.13), (2.88±0.32), (1.60±0.29), (1.30±0.35), and (1.32±0.10) mmol·L-1, respectively; the alanine aminotransferase (ALT) levels were (74.64±9.31), (140.20±23.74), (88.67±13.67), (78.18±17.66), and (73.58±16.15) IU·L-1, respectively; the aspartate aminotransferase (AST) levels were (106.33±26.77), (227.32±20.51), (124.58±13.63), (138.37±18.08), and (115.54±27.14) IU·L-1, respectively. Compared with the model group, the differences of above indicators in the experimental group were all statistically significant (all P<0.01). In HE staining, hepatocytes were arranged in a relatively orderly and dense manner, with a significant reduction in cytoplasmic vacuoles. The aforementioned indicators in the ΔCASP8 experimental group showed no statistically significant differences compared to the ΔCASP8 model group (all P>0.05). There was also no significant difference in the degree of hepatocyte degeneration between the two groups.
CASP8 protein is the key target of HSK31679 in the treatment of MASH. HSK31679 alleviated MASH-related hepatic inflammatory symptoms by binding to CASP8 protein and reducing its activity.
To clarify the role of acyl-CoA thioesterase 8 (ACOT8) across cancers, particularly its prognostic value, and its links to ferroptosis and the immune microenvironment in prostate cancer (PCa).
Using data from The Cancer Genome Atlas (TCGA), R software was used to analyze the gene differential expression of ACOT8 in pan-cancer and the correlation between prognosis. The single sample gene set enrichment analysis (ssGSEA), cell-type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and tumor immune dysfunction and exclusion (TIDE) algorithms were employed to assess correlations with ferroptosis and immune cell infiltration.
ACOT8 was upregulated in 11 cancers and high expression predicted poor survival, most significantly in PCa. In PCa, ACOT8 expression was negatively correlated with ferroptosis activity and positively correlated with immunosuppressive cells.
ACOT8 is a poor prognostic marker in PCa, potentially by inhibiting ferroptosis and promoting an immunosuppressive microenvironment.
To establish a colloidal gold immunochromatographic method for the rapid detection of cotinine in urines.
To prepare the colloidal gold-labeled antibody probe, optimization of the pH value and the amount of antibody labeling (COT-Mab) was carried out. Following this, the coating concentrations of the cotinine antibody (COT-BSA) for the test (T) line and the sheep anti-mouse immunoglobulin G (IgG) for the control (C) line were also optimized. Subsequently, a colloidal gold immunochromatographic strip was assembled. Finally, the sensitivity of the strip was evaluated.
The optimal conditions established for the colloidal gold immunochromatographic strip were as followings, pH value of 6.5, COT-Mab concentration of 10.00 μg·mL-1, COT-BSA concentration of 0.10 mg·mL-1, and sheep anti-mouse IgG concentration of 1.00 mg·mL-1. The visual detection limit and the cut-off value were 0.01 and 0.20 μg·mL-1, respectively. Within 15 minutes, this method enabled qualitative analysis of cotinine in urines.
The method has good specificity and accuracy, as well as convenient operation and excellent reproducibility, which can be used for on-site detection and rapid initial screening of smokers and non-smokers during drug clinical trials.
To provide anticoagulation recommendations and optimize pharmacotherapy for a patient with lower extremity arterial embolism following aortic valve replacement by integrating pharmacogenomics and drug-drug interactions with medication education.
A clinical pharmacist participated in the anticoagulation therapy and medication monitoring for a patient who underwent emergency surgery due to lower extremity arterial embolism after mechanical aortic valve replacement. Based on an analysis of the patient′s individual condition and clinical characteristics, and with reference to guidelines and evidence-based literature, the clinical pharmacist guided the perioperative anticoagulation regimen. Factors influencing the effect of warfarin were also analyzed to optimize its dosage.
The patient′s lower extremity arterial embolism improved, and the patient was discharged with favorable follow-up outcomes.
This case provides a reference for clinical pharmacists in managing anticoagulation therapy for patients with lower extremity arterial embolism after mechanical heart valve replacement.
In the context of "internet plus health care", the annual internet outpatient prescriptions of a tertiary children′s hospital (Beijing Children′s Hospital affiliated to Capital Medical University, hereinafter referred to as the hospital) were taken as the objects, and the rationality of prescriptions was analyzed based on the rational drug use system, and the types, causes and drug characteristics of unreasonable treatments were identified to provide data support for the rational drug use management of pediatric Internet outpatient.
All prescriptions from the hospital′s internet outpatient hospital information system (HIS) in 2024 were collected and summarized. Review results were obtained by relying on the Puhua Hecheng Rational Drug Use System, and true positive irrational prescriptions were determined by combining with pharmacists′ manual re-evaluation. Statistical analysis was performed using Excel software.
A total of 58 560 internet outpatient prescriptions were included. The rational drug use software reviewed 1 334 machine-screened positive irrational prescriptions, and 438 true-positive irrational prescriptions were confirmed after manual re-evaluation, with an overall irrational rate of 0.75%. Among the 438 prescriptions, 93.61% involved only one irrational drug item, and a total of 559 medication problems were detected. Among these, inappropriate indication accounted for the highest proportion (63.51%), which was identified as the primary factor by Pareto analysis. Among the problems of inappropriate dosage and usage, 80.22% involved two combined issues (primarily single-dose overdose and daily-dose overdose, accounting for 61.54%). Inappropriate administration route was mainly attributed to non-standard labeling of "as needed" (70.00%), primarily involving nebulized drugs and nutritional supplements. The top three medications involved in irrational prescriptions were all nutritional supplements and vitamins, with this category ranking first among medication classifications.
The overall rationality of prescriptions in the hospital's pediatric internet-based outpatient service is relatively high. However, inappropriate indications and non-standard dosage and usage remain core issues. Targeted optimization of rational drug use system rules, enhanced pharmaceutical intervention, strengthened physician training, and improved remote consultation processes are needed to enhance medication safety and achieve continuous improvement.
The conjugation and integration of functional molecules have emerged as a core innovative direction in the biomedical field, driving the innovation and upgrading of biotechnology across multiple domains including imaging, detection, and therapy. As a class of novel functional biomolecules, antibody-oligonucleotide conjugates (AOCs) achieve the precise combination of monoclonal antibodies and oligonucleotides through chemical conjugation or bioengineering technologies. They not only inherit the advantage of antibodies in specific targeted delivery but also possess the gene expression regulation function of oligonucleotides, gaining increasing attention in the field of modern biotechnology in recent years. This article systematically sorts out the structural composition, core characteristics, and key technological breakthroughs of AOCs, focusing on analyzing their application scenarios and research status in clinical detection and disease treatment, aiming to provide a reference for the independent research and development, technological innovation, and industrial transformation of AOC drugs in China.
Signal transducer and activator of transcription 3 (Stat3), as a crucial transcription factor, plays a core regulatory role in regulating the cell cycle and various cellular processes such as proliferation, survival, differentiation, and inflammatory responses. Aberrant activation of Stat3 is closely related to the occurrence and development of many tumors. Meanwhile, the activity and stability of Stat3 are influenced by its post-translational modifications, including phosphorylation, acetylation, methylation, etc., among which phosphorylation is one of the most critical regulatory mechanisms. Under pathological and physiological stimuli, phosphorylation modifications can alter the structure of Stat3 in different cells, thereby determining specific gene programs. This process leads to the activation of Stat3 and promotes tumor cell proliferation, etc. This article focuses on the phosphorylation modification of Stat3, systematically elaborating on the regulatory mechanisms of its main phosphorylation sites (tyrosine 705 site and serine 727 site), as well as its roles in tumor cell cycle regulation, apoptosis inhibition, angiogenesis, invasion and metastasis, and tumor microenvironment remodeling. At the same time, it explores tumor treatment strategies targeting Stat3 phosphorylation, providing theoretical references for tumor mechanism research and clinical treatment.
Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by excessive hepatic lipid accumulation resulting from multiple etiological factors. In recent years, changes in lifestyle have contributed to a rising incidence of NAFLD, making it a significant public health concern. Traditional Chinese medicine (TCM), with its multi-component, multi-pathway, and multi-target characteristics, has demonstrated unique advantages and research value in the prevention and treatment of NAFLD. Polygonum cuspidatum is a representative herbal medicine in this context and has been confirmed to possess various pharmacological activities, including anti-inflammatory, antioxidant, and hepatoprotective effects. However, its specific active components and mechanisms of action remain incompletely elucidated. Therefore, this article systematically reviews Chinese and English literature on Polygonum cuspidatum and its active components in the treatment of NAFLD. The results indicate that the core active components of Polygonum cuspidatum against NAFLD include resveratrol, polydatin, emodin, among others. The mechanisms involve multiple pathways, such as the regulation of lipid metabolism, improvement of glucose metabolism and insulin resistance, anti-inflammatory effects, antioxidant stress response, and modulation of gut microbiota. This review aims to provide insights and references for further mechanistic research and clinical application of Polygonum cuspidatum.
The prevention and treatment of perioperative myocardial injury primarily rely on hemodynamic management and conventional cardiovascular medications, yet limitations remain, such as constraints in intervention timing, significant individual response variability, and the irreversible effects or notable adverse reactions associated with some drugs. As an ultra-short-acting, highly selective β1-receptor blocker, esmolol offers rapid onset, a short half-life, and precise controllability. It not only effectively stabilizes heart rate and blood pressure but may also exert myocardial protective effects through multiple pathways, including regulating myocardial oxygen supply-demand balance, suppressing inflammatory responses, and mitigating cellular apoptosis. This article reviews recent domestic and international studies, summarizing the mechanisms of perioperative myocardial injury, the myocardial protective effects of esmolol, and its potential molecular pathways. The aim is to provide new perspectives and a theoretical basis for optimizing perioperative cardiac protection strategies.
Drug safety spans the full lifecycle of drug research and development, manufacture, distribution and usage, serving as both the cornerstone of public health maintenance and a core issue in regulatory science. Traditional drug safety monitoring models face numerous challenges regarding data processing efficiency, agility in risk identification and comprehensiveness. However, the advancement of artificial intelligence (AI) technologies offers unprecedented opportunities for this field. From a full lifecycle perspective, this paper systematically reviews and analyzes the key technologies and application progress of AI in safety assessment across three stages: preclinical research, clinical trials, and post-marketing pharmacovigilance. Currently, AI technologies, represented by machine learning and natural language processing, have demonstrated significant potential in drug toxicity prediction, the automated identification of adverse events, and real-time safety monitoring. Nevertheless, uneven data quality, insufficient model interpretability, and imperfect regulatory compliance remain the primary bottlenecks hindering the widespread application of AI in the field of drug safety. Future development will focus on the fusion of multi-modal data, the enhancement of model interpretability, and the application of federated learning for privacy protection, with the aim of constructing a more precise and reliable intelligent drug safety monitoring system.
Thioctic acid is widely used in clinical treatment of diabetic peripheral neuropathy. The human bioequivalence (BE) study of thioctic acid tablet should follow the relevant regulations and guidelines, and fully consider the particularity of the clinical use of this product. It is recommended to adopt a single dose, two preparations, two sequences, partial or complete repeated crossover study design, and select the reference preparations that have been publicly released for the fasting test. In addition, researchers should pay attention to the Chinese version of The Internationevl Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M13A and its Q&A document, as well as the BE study ideas of similar drugs. This article takes the BE study of thioctic acid tablet as an example to provide in-depth guidance for the research.
To give patients a more scientific instruction of prescription drugs, drug regulatory authorities in developed countries such as Europe, the United States, and Japan are actively promoting the establishment of patient labeling system. Unlike professional labeling, patient labeling uses easy-to-understand language to help patients understand the most critical information about the drug, thereby enabling safer use of prescription drugs. This article focuses on the U.S. Food and Drug Administration(FDA)′s patient labeling system, briefly introducing the main content and relevant requirements of different types of patient labeling, such as the medication guides (MG), patient package inserts (PPI), instructions for use (IFU), and consumer medication information (CMI). It also provides a detailed introduction to the scope of application, specific content, and format requirements of the patient medication information (PMI) that the FDA is currently promoting, while giving a brief explanation of the patient labeling systems of other drug regulatory authorities (such as the European Union and Japan). PMI is a new form of patient labeling further optimized by the FDA based on previous experience in patient labeling work, and it plans to gradually unify and replace the original MG and PPI. In China, the State Council issued and implemented the Law of the People′s Republic of China on the Construction of Accessible Environments in 2023, requiring drug manufacturers and operators to provide labels and instructions in accessible formats such as audio, large print, braille, and electronic versions. In the same year, the National Medical Products Administration (NMPA) issued a public notice to promote the pilot work on aging-friendly labeling. By sorting out and summarizing the practical experience of the FDA′s patient labeling system and comparing it with the current pilot work on aging-friendly labeling in China, this article provides insights and references for promoting the establishment of a patient labeling system in China.
To summarize and analyze clinical development strategy and the key considerations of clinical trial design of drugs for the treatment of corona virus disease 2019 (COVID-19) at home and abroad in recent years, including ribonucleic acid (RNA) polymerase inhibitors, 3CL protease inhibitors, and neutralizing antibodies, etc. In general, the confirmatory clinical trials for therapeutic drugs for COVID-19 typically adopt a randomized, double blind, placebo-controlled clinical trials using a superiority design. Based on their therapeutic positioning, most trials mainly enroll patients with mild to moderate COVID-19, with or without high-risk of complications, and the primary efficacy endpoints are the proportion of patients hospitalized or mortality by an appropriate time point, or the time to sustained clinical recovery assessed over an appropriate duration. Through reviewing drug development during the COVID-19 pandemic, this paper summarized the considerations and changes for clinical research and development, as well as the focus of clinical trial design for new drugs in the treatment of COVID-19, in the context of emerging and sudden major infectious diseases, hoping to provide references for drug research and development.
To conduct a statistical analysis of clinical trial visit time windows and propose targeted recommendations based on risk management from the perspective of the institutional office, so as to provide references for clinical research practice.
Data of drug clinical trial projects undertaken by a single institution from 2018 to 2024 were collected. Visit time windows were statistically analyzed and compared across the screening phase, visit phase, and follow-up phase. A risk classification standard for time windows was established by integrating management practice, regulatory requirements, and relevant literature. Corresponding recommendations were put forward for sponsors, researchers, participants, and the institutional office based on this classification.
A total of 137 projects were included, with the number of visits ranging from 1 to unlimited. Visit modalities included on-site visits and remote visits (telephone visits). The most prevalent time windows in each phase were 28 days (45.99%) for the screening phase, 3 days (62.26%) for the visit phase, and 7 days (68.93%) for the follow-up phase. The risk classification results were as follows: extremely high-risk time windows (1 to 30 minutes in the visit phase), high-risk time windows (42 to 183 days: before screening in the screening phase, 1 to 24 hours in the visit phase, and 1 to 3 days in the follow-up phase), medium-risk time windows (1 to 7 days: before screening in the screening phase, 1 to 3 days in the visit phase, and 5 to 10 days in the follow-up phase), and low-risk time windows (14 to 35 days: before screening in the screening phase, 4 to 14 days in the visit phase, and 14 to 30 days in the follow-up phase). Compared phase Ⅱ with phase Ⅲ or phase Ⅳ, statistically significant differences were all observed in the distribution of visit windows during the visit phase (all P<0.05). Based on this classification, the institutional office recommends that all parties adopt strategies of scientific design, risk-based response, and closed-loop management, and deeply understand and actively cooperate with each other for different risk levels of time windows.
Significant differences exist in visit time windows across different phases of clinical trials. Risk classification and targeted responses from all parties can effectively ensure the quality of clinical trial data and the rights and interests of participants.
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