Latest ArticlesTo sequence a vancomycin-resistant Enterococcus faecium and analyze the vanM gene cluster carried on its plasmid as well as the genes conferring advantage in nutrient utilization.
The broth microdilution method was used to perform drug susceptibility tests on strain 15P371 and its transconjugant J15P371. Subsequently, whole-genome sequencing was conducted using Nanopore technology for both strains, followed by analysis of the resistant plasmid sequences. Bacterial growth experiments were carried out to verify the advantage in intestinal nutrient utilization.
Strain 15P371 is a vancomycin-resistant strain carrying 6 copies of the vanM gene cluster. Its transconjugant J15P371 can tolerate a higher concentration of vancomycin but only harbors 3 copies of the vanM gene cluster. Genes conferring advantage in intestinal N-acetylgalactosamine utilization are present on the resistant plasmid.
In vanM-type vancomycin-resistant strain, the copy number of resistance genes is variable during conjugative transfer. The plasmid carrying genes with advantage in N-acetylgalactosamine utilization confer growth advantage to the host bacteria.
To explore the mechanism by which processed Radix Hedysari and vinegar-processed Rhizoma Curcumae inhibit angiogenesis in colitis-associated colorectal cancer (CAC).
Sixty SPF-grade C57BL/6J mice were randomly divided into six groups (A-F), A: Blank control; B: Model group [Azoxymethane (AOM)/Dextran sodium sulfate (DSS) AOM/DSS group]; C: Sulfasalazine group; D: Fried Astragalus group; E: Fried Astragalus-Vinegar Curcuma (4∶1) group; F: Curcuma zedoaria group. Each group contained 10 mice. A CAC mouse model was induced using combined AOM and DSS. Simultaneously, each treatment group received intervention, the blank group received 0.9% sodium chloride solution. The experiment concluded after 17 weeks of intervention. Collagen fiber area expression in colon tissues was assessed using Masson’s trichrome staining. Microvascular density in colon tissues was determined via immunohistochemistry. Serum vascular endothelial growth factor(VEGF) and nitric oxide(NO) levels were measured using enzyme linked immunosorbent assay(ELISA). Key proteins in the phosphatidylinositol-3-kinase/ protein kinase B(PI3K/AKT) pathway and VEGF expression were detected by Western blotting (WB).
After 17 weeks of pharmacological intervention, the microvessel counts in the blank group, model group, sulfasalazine group, honey-fried Radix Hedysari-vinegar-processed Rhizoma Curcumae (4:1) group, honey-fried Radix Hedysari group, and vinegar-processed Rhizoma Curcumae group were (23.20±4.21), (73.60±13.52), (44.80±2.78), (33.40±6.31), (41.60±3.36), and (47.80±7.29), respectively. The serum VEGF concentrations were (83.03±24.13), (153.61±18.69), (115.08±11.43), (87.03±25.24), (91.33±32.37), and (101.93±19.74) pg·mL-1, respectively. The serum NO levels were (28.46±5.91), (40.62±2.28), (30.62±6.54), (29.18±5.37), (30.87±5.30), and (32.29±3.43) μmol·L-1, respectively. Compared with the blank group, the model group exhibited significant increases in the collagen fiber staining area and microvessel density in colonic tissue, markedly elevated serum VEGF and NO levels, and significantly enhanced phosphorylation of PI3K, AKT, and mTOR as well as upregulated VEGF expression in colonic tissue. In comparison with the model group, the honey-fried Radix Hedysari-vinegar-processed Rhizoma Curcumae (4∶1) group, honey-fried Radix Hedysari group, and vinegar-processed Rhizoma Curcumae group demonstrated significant reductions in the collagen fiber area and microvessel count in colonic tissue, decreased serum VEGF and NO concentrations, and markedly suppressed phosphorylation of PI3K, AKT, and mTOR along with downregulated VEGF expression in colonic tissue (P<0.05 or P<0.01).
The combined use of processed Radix Hedysari and vinegar-processed Rhizoma Curcumae exerts a better anti-CAC effect than the single herb. Its mechanism is closely related to regulating the expressions of key proteins in the PI3K/AKT signaling pathway, thereby inhibiting angiogenesis in colitis-associated colorectal cancer.
To compare the safety and efficacy of two different companies’ sodium hyaluronic acid gels for correcting moderate to severe nasolabial folds, and evaluate the non-inferiority of the test device to the control device.
This study included healthy subjects with the desire for nasolabial fold beauty who visited the hospital from March to August 2019, the subjects were randomly assigned to the test group and the control group at a ratio of 1∶1, and followed up to 12 months after a single injection sodium hyaluronic acid gel. The primary efficacy evaluation index was the effective rate of wrinkle improvement in the bilateral nasolabial area before and 6 months injection. The secondary efficacy evaluation indexes were the Wrinkles Severity Rating Scale (WSRS) scores of wrinkle improvement at different time points by the investigator and the subjects, and the Global Aesthetic Improvement Scale (GAIS) scores.
A total of 137 subjects were included per protocol set, with 70 in the test group and 67 in the control group, respectively. Compared with the baseline, the effective rates of improvement of one grade or above in the test group and the control group were 94.29% (66 cases/70 cases) and 94.03% (63 cases/67 cases), respectively, with a difference of 0.26% between the two groups, and the 95% limit of the difference (asymptotic normal) was [-0.08, 0.08], with the lower limit greater the non-inferiority limit of -10%, and the efficacy of the test group was not inferior to that of the control group. At 6 months post-injection, the investigator’s WSRS scores on the left of the test and control groups were (2.13±0.64) and (2.22±0.6) points, respectively, on the right side were (2.23±0.68) and (2.3±0.6) points; the subjects’ WSRS scores on the left were (2.24±0.79) and (2.32±0.84) points, on the right side were (2.18±0.77) and (2.29±0.76) points, respectively. The investigator’s GAIS of the test and control groups that were regarded as improved were 98.57% (69 cases/70 cases) and 97.01% (65 cases/67 cases), respectively; the subjects’ GAIS that were regarded as improved were 88.5% (62 cases/70 cases) and 86.57% (58 cases/67 cases), respectively, and there was no statistically significant difference between the groups all (P>0.05). In addition, there was no significant difference in the incidence of adverse reactions/adverse events between the two groups (P>0.05).
The effectiveness of the test group sodium hyaluronate gel for correcting moderate to severe nasolabial folds was not inferior to that of the control. And it has similar safety.
To evaluate the bioequivalence of clindamycin hydrochloride capsules test formulation and reference formulation in healthy subjects under fasting and postprandial conditions.
A randomized, open-label, single-dose, two-cycle crossover study was used in this study. A single dose of clindamycin hydrochloride capsules was administered in fasting and postprandial conditions, and the main pharmacokinetic parameters of clindamycin were determined by liquid chromatography tandem mass spectrometry to evaluate the bioequivalence of the two preparations.
Twenty- four healthy subjects were involved in the fasting and fed groups, respectively. The main pharmacokinetics (PK) parameters of the test formulation and reference formulation in the fasting group: Cmax were (2 174.17±616.64) and (2 288.75±678.73) ng·mL-1, AUC0-t were (8 080.29±3 707.51) and (8 496.10±4 801.26) h·ng·mL-1, AUC0-∞ were (8 333.89±3 838.97) and (8 790.21±4 987.28) h·ng·mL-1. The ratio of geometric mean and its 90% confidence interval were 95.27% (89.93%-100.93%), 97.75% (90.39%-105.70%), and 97.51% (90.13%-105.50%). The main PK parameters of the test formulation and reference formulation in the fed group: Cmax were (1 860.00±349.00) and (2 069.04±504.25) ng·mL-1, AUC0-t were (7 829.93±1431.81) and (8 317.23±2 267.65) h·ng·mL-1, AUC0-∞ were (8 053.74±1 486.71) and (8 543.98±2 328.35) h·ng·mL-1. The ratio of geometric mean and its 90% confidence interval were 91.56% (82.23%-101.95%), 96.41% (88.27%~105.31%), and 96.47% (88.14%~105.58%). The 90% confidence intervals of the geometric mean ratios of the main PK parameters of the test preparation and reference preparation for clindamycin hydrochloride capsules in the fasting group and fed group were all within 80.00% to 125.00%. The incidence of adverse events for the test and reference preparations in the fasting group were 25.00% and 20.80%, respectively, while in the postprandial group, they were 25.00% and 33.30%, respectively.
In the fasting and postprandial states, clindamycin hydrochloride capsules are bioequivalent to the original reference preparation.
To establish a highly efficient, sensitive, and accurate ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method to determine the concentration of melatonin (MLT) in human plasma with heparin sodium.
The concentration of melatonin in plasma was measured using UHPLC-MS/MS. Plamsa sample preparation was done by protein precipitation using acetonitrile, its isotope melatonin-d4 (MLT-d4) was used as the internal standard (IS). Using UPLC BEH C18 (2.1 mm×50.0 mm, 1.7 μm) reverse phase chromatography column, gradient elution was performed with a mobile phase consisting of acetonitrile-water (0.05 mM Ammonium fluoride) at a flow rate of 0.4 mL·min-1 for 3 min. MLT was monitored using positive electrospray triple quadrupole mass spectrometer via multiple reaction monitoring (MRM) mode. The monitored transitions were set at m/z 233.0→174.0 for MLT. Moreover, the IS was set at m/z 237.2→178.2. This method was applied in a single-center, randomized, open-label, single oral dose pharmacokinetic trial, with 12 subjects in each group for fasting and after meals, administered a dose of 2 g (containing 4 mg of melatonin). Statistical analysis of pharmacokinetic parameters Cmax (ΔCmax), AUC0-t (ΔAUC0-t), and AUC0-∞ (ΔAUC0-∞) using WinNonlin version 8.3 or above or SAS version 9.4 or above.
The achieved lower limit of quantification was 50.00 pg·mL-1. The validated method had an excellent linearity in the range of 50.00-50 000.00 pg·mL-1 for MLT y=2.00x+1.12×10-4 (r2>0.999 4). The results of the intra-batch and inter-batch precision showed that the relative standard deviation (RSD) at different concentrations did not exceed 5.77%, and the accuracy was between 92.11% - 102.01% . The extraction recoveries of low, medium and high quality control samples of MLT were 103.35%, 113.75% and 131.21%, respectively. The coefficient of variation was 12.13%. No significant matrix effect was found. Through the pharmacokinetic study of 12 healthy humans, it was found for the first time that after taking the same dose of melatonin, the postprandial Cmax was about 50% of that of fasting, but the AUC was very similar, indicating that food might affect the absorption and metabolism of melatonin in the body.
This method has strong specificity, good precision and high sensitivity, which can quickly and accurately determine the content of melatonin in human plasma with heparin sodium, and is used for the detection of human blood drug concentration and pharmacokinetics of melatonin.
To explore the impact of necrotic apoptosis-related long non-coding RNA (lncRNA) on the prognosis of hepatocellular carcinoma (HCC) in high-risk populations.
LncRNAs were identified by co-expression analysis of immune genes with gene expression and clinical data from the cancer genome atlas program (TCGA) database. A risk model was established through univariate and multivariate cox proportional hazards regression model (Cox), as well as Lasso regression analysis. Patients were screened from TCGA database and divided into high-risk group and low-risk group. Combined with necrotic apoptosis-related lncRNA features, a highly predictive nomogram was created.
By analyzing data from the TCGA, a total of five lncRNAs (TMCC1-AS1, AC026412.3, AC026356.1, AC100872.2, and FOXD2-AS1) were identified as potential biomarkers. Nomogram was created, and its predictive efficiency was assessed using a calibration curve. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) for predicting 1-year, 3-year, and 5-year survival rate were 0.781, 0.663, and 0.686, respectively (P<0.001).
Risk model constructed based on five necrotic apoptosis-related lncRNAs may predict prognosis in HCC patients.
The safety and efficacy of tranexamic acid in the perioperative period of burn patients remain controversial. This study aimed to investigate the safety and efficacy of tranexamic acid in perioperative burn patients.
A systematic search was conducted in Pubmed, Embase, Cochrane Library, China national know-ledge infrastructure (CNKI), Wanfang, and other databases up to March 1, 2025, for studies on the use of tranexamic acid in perioperative burn care. The primary outcomes included total perioperative blood loss, perioperative blood transfusion events, operative time, all-cause mortality, and incidence of adverse events. Meta-analysis was performed using RevMan 5.4.1, with risk of bias assessed using Cochrane’s ROB 2 tool and Robins-1 tool.
Seven studies were included, comprising a total of 465 cases (218 in the tranexamic acid intervention group and 247 in the control group). The findings demonstrated that the total perioperative blood loss in the tranexamic acid group was significantly lower than in the control group [MD=-165.01, 95% confidence interval (CI) (-210.13 to -119.89), P<0.001]. Additionally, tranexamic acid reduced operative time [MD=-8.32, 95% CI (-14.55 to -2.09), P=0.009] and perioperative blood transfusion events (OR=0.26, 95% CI 0.15-0.44, P<0.001), without increasing all-cause mortality (OR=0.67, 95% CI 0.33 to 1.36, P=0.27).
Tranexamic acid is effective in reducing total perioperative blood loss, shortening operative time, and decreasing the risk of perioperative blood transfusion events in burn patients, without increasing all-cause mortality. Thus, tranexamic acid can serve as a valuable adjunct in perioperative management for burn patients.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by persistent airflow limitation. Its pathogenesis is complex and involves multiple pathological processes such as oxidative stress, inflammatory response and apoptosis. The mitogen-activated protein kinase (MAPK) signaling pathway plays a significant role in regulating cell growth, proliferation, differentiation and apoptosis. Modern research has confirmed that traditional Chinese medicine can exert therapeutic effects on COPD by intervening in the MAPK signaling pathway. This article reviews the regulatory mechanism of the MAPK signaling pathway on COPD and the intervention effect of traditional Chinese medicine on COPD in recent years, aiming to provide research basis for the development of new traditional Chinese medicine and the clinical application of traditional Chinese medicine in the treatment of COPD.
The high morbidity and mortality of gastric cancer seriously affect and threaten the public's life and health. Precancerous lesions of gastric cancer (PLGC) is a key stage in the process of gastric mucosal carcinogenesis, and it is also a "golden turning point" before the formation of gastric cancer. Early and effective intervention has become an important way and research focus for the prevention and control of gastric cancer. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway is involved in a variety of biological processes such as inflammatory response, angiogenesis, autophagy level and apoptosis. Studies have confirmed that this pathway is abnormally activated in PLGC and can promote the malignant progression of the disease to gastric cancer by regulating a variety of pathways, which can be used as a potential target and effective way for the prevention and treatment of PLGC. In recent years, traditional Chinese medicine has achieved many research results in delaying or even reversing PLGC by targeting the PI3K/Akt signaling pathway. Based on the PI3K/Akt signaling pathway, this paper systematically expounds the role of this signaling pathway in PLGC and the research progress of traditional Chinese medicine intervention, in order to provide reference for the clinical treatment of this disease and drug development and application.
Osteoarthritis, a degenerative bone disease commonly seen in the elderly, is particularly prevalent in weight-bearing joints such as the knee. Its etiology is multifactorial and characterized by pathological changes in the joint structure, including destruction and degeneration of articular cartilage, inflammatory response and formation of bone capillaries. Up to now, clinical treatment for osteoarthritis is mainly symptomatic treatment and pain relief, and there is no exact therapy that can reverse the pathological process of cartilage damage in osteoarthritis. In recent years, domestic and foreign scholars have found that mitochondria, as important organelles of chondrocytes, plays an important role in the process of cell metabolism, proliferation and apoptosis. It is also pointed out that mitochondrial autophagy imbalance is an important factor leading to cartilage damage in joints. Meanwhile, several basic experiments have shown that Chinese medicine exhibits the potential to protect cartilage by targeting the regulation of mitochondrial autophagy, thus showing positive results in the prevention and treatment of osteoarthritis. However, studies on this area have not been systematically elaborated. In view of this, the authors will systematically elaborate on the effects of mitochondrial autophagy on the development of osteoarthritis and the role of TCM in interfering with mitochondrial autophagy in the treatment of osteoarthritis, with the aim of providing new ideas and methods for the development of new medicines and therapeutic strategies for the treatment of osteoarthritis with TCM.