Latest ArticlesTo systematically analyze the linear plasmid-related studies published from 1994 to 2023 by using bibliometric methods, and to sort out the research pattern, core forces and development context of this field.
A total of 989 linear plasmid-related literatures indexed in the Web of Science Core Collection were selected as research objects. Bibliometric analysis was carried out from the dimensions of country, institution, journal, author and keyword by using CiteSpace (a literature analysis software) and GraphPad Prism (a graphing software).
Linear plasmids were taken as the core research object. The United States and Germany together contributed 53% of the relevant literature, with the USA National Institutes of Health (NIH) ranking first in the number of publications (50 papers). Journal of Bacteriology has published 80 papers on this topic, and German scholar Meinhardt Friedhelm (16 papers) is the core author in this field. Among them,Borrelia burgdorferi is the classic research microorganism, and the research hotspots include comparative genomics, replication and horizontal transfer mechanisms, and gene regulation. In addition, the dissemination of antibacterial drug resistance genes mediated by linear plasmids and the evolution of resistant plasmids have also attracted great attention.
Over the past 30 years, research on linear plasmids has evolved from sequence analysis to functional mechanism exploration, and has continuously integrated new technologies. However, the current research still has limitations such as insufficient breadth and depth. In the future, international cooperation should be strengthened to conduct in-depth research on linear plasmids, which can provide theoretical support for the formulation of drug resistance prevention and control strategies and the development of new antibacterial drugs.
Lidocaine and Prilocaine Cream is a topical cream preparation made by a eutectic mixture of lidocaine and prilocaine in a ratio of 1∶1 by weight. Lidocaine and prilocaine are amide-type local anesthetic agents. Both lidocaine and prilocaine stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. It is clinically used mainly for local anesthesia of the skin for punctures and superficial surgical procedures. Considering this product is a topical preparation, when evaluating its quality and efficacy consistency with the reference preparation, a stepwise comparative study be conducted based on the drug's characteristics, including pharmaceutical, nonclinical, and/or necessary clinical comparative studies, to support the equivalence evaluation of the generic drug the reference preparation. Clinical comparative studies of this product can be human bioequivalence (BE) studies with the reference preparation. In BE studies, the study type, dose and method of administration, application time, PK blood sampling, skin reaction observation, bioequivalence evaluation, and reactivity evaluation should be fully considered and reasonably designed. This article, based on the characteristics of Lidocaine and Prilocaine Cream and the BE study examples before the domestic launch of the same variety of generic drugs, systematically explores the general design requirements and related considerations for the bioequivalence study of this product.
Acetylcysteine is a commonly used clinical drug, and its free thiol group can break the disulfide bond (S-S) in the glycoprotein peptide chain in sputum, thereby reducing sputum viscosity and promoting sputum excretion. It is an endogenous substance. When conducting bioequivalence studies, it is necessary to fully consider and design aspects such as the research type, dosage, blood collection point design, bioequivalence evaluation, etc., and fully evaluate the impact of endogenous acetylcysteine on bioequivalence evaluation. This article integrates the pharmacokinetic (PK) characteristics of acetylcysteine granules along with the bioequivalence research conducted on its generic version prior to domestic marketing. Through this approach, it comprehensively explores the general design requirements and key considerations for conducting bioequivalence studies on this product.
Efgartigimod, as a novel FcRn inhibitor, can improve neuromuscular transmission in patients with generalized myasthenia gravis (gMG) by accelerating the degradation of pathogenic IgG antibodies. Although clinical trials have confirmed its efficacy and good tolerability, its safety profile in the real-world setting requires comprehensive evaluation. This study utilized data from the U.S. FDA Adverse Event Reporting System (FAERS) to investigate and assess potential adverse event (AE) signals associated with Efgartigimod. The aim was to evaluate its real-world safety characteristics and provide evidence for clinical safe medication use and risk monitoring.
Reports listing Efgartigimod as the primary suspected drug were extracted from Q1 2020 to Q4 2023. After deduplication and terminology standardization, disproportionality analysis was conducted using three methods: Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM), to identify significant signals at both the System Organ Class (SOC) and Preferred Term (PT) levels. Important Medical Events (IMEs) were also screened.
A total of 788 individual case safety reports involving 13 551 AEs were included. At the SOC level, the strongest signals were for nervous system disorders (ROR=5.12) and neoplasms (ROR=4.78). At the PT level, multiple strong signals were identified, including myasthenic crisis (ROR=2 269.29), bulbar paralysis (ROR=275.64), and thymoma (ROR=170.02). IME analysis further confirmed these events as high-priority safety concerns.
This study identified several potential new safety signals for Efgartigimod in the neurological, oncological, and immunological domains, suggesting that clinicians should remain vigilant about adverse reactions related to these organ systems and providing a basis for further targeted safety research.
Gene therapy drugs based on adeno-associated virus (AAV) have become the most widely used viral vectors for in vivo gene therapy in clinical applications. Until July 2025, nine AAV-based gene therapy drugs have been approved globally, with many more in research or clinical trials. This article analyzes the basic characteristics, adverse reactions, and risk management strategies of AAV gene therapy drugs, aiming to provide valuable insights for risk assessment and mitigation in this field.
Decentralized clinical trials (DCT) have shown a rapid growth trend in recent years due to their advantages such as being geographically unrestricted, enhancing research efficiency, and reducing research costs. The United States has a significant development advantage in this field, with a clear concentration trend. China is still in its infancy in this area, lacking practical experience and summaries. This study takes the "Multicenter Prospective Open Randomized Controlled Clinical Study on the Early Intervention of Lianhua Qingwen Granules in Acute Pharyngitis Patients" as an example, and through the implementation of DCT digital management based on the internet platform, it sorts out and summarizes the key links in conducting DCT, explores the technical aspects and applicable fields of DCT in China, and provides practical references for accelerating the resolution of the bottlenecks in promoting DCT.
To evaluate the differences in clinical efficacy between continued azithromycin therapy and switching to tetracycline antibiotics (doxycycline/minocycline) in children with macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP).
Children with MUMPP hospitalized in our hospital were divided into treatment group and control group according to the secondary antibiotic selection after ineffective initial macrolide treatment for 72 hours. The control group continued to receive azithromycin for injection at a dose of 10 mg·kg-1 once a day for a 7-day course of treatment. The treatment group was switched to oral tetracycline antibiotics: minocycline capsules at 2 mg·kg-1 twice a day, or doxycycline enteric-coated capsules at 2.2 mg·kg-1 twice a day, with a total course of 10 days. The time to defervescence, treatment effectiveness rate, and changes in white blood cell count (WBC), neutrophil percentage (NE%) and C-reactive protein (CRP) levels were compared between the two groups, and a safety evaluation was performed.
A total of 107 cases were included in this study, with 87 cases in the treatment group and 20 cases in the control group. The total clinical effective rates of the treatment group and the control group were 90.80% (79 cases /87 cases) and 85.00% (17 cases /20 cases), respectively, and the difference was not statistically significant (P>0.05). The antipyretic time of the treatment group and the control group was (6.82±1.71) and (7.75±2.12) days, respectively, with statistically significant difference (P<0.05). Before conversion therapy, the white blood cell counts of the control group and the treatment group were (8.58±3.67) and (6.77±2.59) ×109·L-1, respectively, and the CRP levels were (14.44±8.58) and (26.43±26.53) mg·L-1, respectively; both differences were statistically significant (all P<0.05). The neutrophil percentages of the control group and the treatment group were (57.93±9.39)% and (62.43±10.79)%, respectively, the lymphocyte percentages were (32.43±8.46)% and (28.60±9.57)%, respectively, the monocyte percentages were (7.63±2.01)% and (7.43±2.53)%, respectively, none of these differences were statistically significant (all P>0.05). The total incidence of adverse drug reactions in the treatment group and the control group was 1.15% and 0, respectively, with no statistically significant difference (P>0.05).
For children with MUMPP, tetracycline antibiotics provide faster fever resolution, but the overall efficacy of both regimens is comparable. Clinical decisions should consider the child’s age (tetracyclines preferred for those ≥8 years) and parental informed consent. Continued azithromycin therapy is recommended in combination with glucocorticoids to control excessive inflammatory responses.
To compare the efficacy and safety of ticagrelor combined with nicorandil versus clopidogrel combined with nicorandil in elderly coronary heart disease (CHD) patients experiencing angina pectoris following percutaneous coronary intervention (PCI).
Patients with post-PCI angina admitted to our hospital were divided into treatment group and control group based on treatment protocols. The control group received clopidogrel bisulfate tablets (75 mg, qd), and nicotardil tablets (5 mg, tid) based on standard post-PCI therapy including aspirin enteric-coated tablets (100 mg, qd), atorvastatin calcium tablets (20 mg, qd). The treatment group received ticagrelor tablets (90 mg, bid), and nicotardil tablets (5 mg, tid) based on the same standard post-PCI therapy. Both groups underwent continuous treatment for 24 weeks. Sublingual nitroglycerin tablets were allowed for acute angina attacks. Primary outcomes included therapeutic efficacy, cardiac function indices, lipid profiles, lipoprotein-associated phospholipase A2 (Lp-PLA2) levels, antiplatelet reactivity and coagulation parameters, Seattle angina questionnaire (SAQ) scores, and incidence of major adverse cardiovascular events (MACE) were compared between the two groups.
A total of 123 patients were enrolled with 59 patients in treatment group and 64 patients in control group. After treatment, the overall response rates in treatment group and control group were 91.53% (54 cases /59 cases) and 78.12% (50 cases/64 cases), respectively. Left ventricular end-diastolic diameter (LVEDD) in treatment group and control group were (44.76±4.23) mm and (46.63±4.13) mm, respectively; left ventricular end-systolic diameter (LVESD) were (30.16±4.22) and (32.57±5.13) mm, respectively; left ventricular ejection fraction (LVEF) were (61.49±6.24)% and (58.49±6.13)%, respectively; cardiac index (CI) were (2.80±0.29) and (2.67±0.27) L·min-1·m-2, respectively; triglycerides (TG) were (1.70±0.21) and (1.82±0.35) mmol·L-1, respectively; total cholesterol (TC) were (5.12±0.56) and (5.41±0.60) mmol·L-1, respectively; low-density lipoprotein cholesterol (LDL-C) were (3.28±0.64) and (3.57±0.58) mmol·L-1, respectively; high-density lipoprotein cholesterol (HDL-C) were (2.74±0.54) and (2.53±0.51) mmol·L-1, respectively; Lp-PLA2 were (231.63±32.47) and (244.89±35.62) ng·mL-1, respectively. Regarding antiplatelet and coagulation parameters, the arachidonic acid inhibition rate (AA-IR) in treatment group and control group were (81.26±15.11)% and (74.52±15.13)%, respectively; adenosine diphosphate inhibition rate (ADP-IR) were (78.56±15.96)% and (70.95±14.57)%, respectively; lower maximum platelet aggregation rate (MPAR) were (26.78±4.82)% and (28.52±4.18)%, respectively; coagulation rate (CR) were (18.04±2.04) and (19.28±2.71) sig·min-1, respectively; SAQ scores were significantly higher in the treatment group across all dimensions: angina stability were (82.80±9.10) and (78.53±8.91) points, respectively; attack frequency were (80.17±12.24) and (75.63±10.22) points, respectively; physical activity limitation were (82.10±10.26) and (77.77±9.99) points, respectively; disease awareness were (74.49±11.25) and (69.13±10.96) points, respectively; and satisfaction were (83.41±10.35) and (78.56±11.49) points, respectively; the difference of the above indexes were all statistically significant (all P<0.05). The total incidence rates of MACE in treatment group and control group were 6.78% (4 cases/59 cases) and 20.31% (13 cases /64 cases), respectively, with statistically significant difference (P<0.05).
Compared with clopidogrel combined with nicorandil, ticagrelor combined with nicorandil exhibits superior efficacy in treating angina pectoris after CHD-PCI in elderly patients, with significant improvements in cardiac function and angina symptoms, as well as favorable safety profiles.
To explore the clinical efficacy and safety of thoracolumbar fascia plane block with ropivacaine hydrochloride injection combined with compound betamethasone injection in elderly patients undergoing lumbar spine surgery during the perioperative period.
The elderly patients admitted to our hospital who underwent posterolateral approach lumbar fusion (PLIF) under general anesthesia due to lumbar degenerative diseases were divided into control group and treatment group according to different anesthesia methods. Both groups of patients received thoracolumbar fascia plane (TLIP) block. Control group was injected with a single dose of 20 mL of 0.375% ropivacaine hydrochloride injection, while treatment group was injected with a single dose of a mixture of 20 mL of 0.375% ropivacaine hydrochloride injection and 5 mg of compound betamethasone injection for TLIP block. The remaining operations were same. The hemodynamic indicators, rehabilitation process indicators, opioid dosage and remedial analgesia conditions, visual analogue scale (VAS) scores at rest and turning over at different time points, stress and immune indicators of the two groups of patients were compared, and safety evaluations were conducted.
A total of 115 cases were screened in this study, with 102 cases enrolled. Among them, 50 cases were enrolled in control group and 52 cases in treatment group. The heart rate (HR) of the control group and the treatment group at T4 were (82.13±10.68) and (74.81±10.19) times·min-1, respectively; and the mean arterial pressure (MAP) were (92.33±9.87) and (88.27±8.92) mmHg, respectively; the recovery time were (36.41±6.97) and (31.87±6.53) min, respectively; and the resting VAS scores at 48 hours after the operation were (2.71±0.88) and (2.56±0.82) points, respectively; the VAS scores at turning over 48 hours after the operation were (3.42±0.97) and (2.88±0.84) points, respectively; the first PCIA time were (20.04±5.67) and (16.79±4.32) hours, respectively; the effective compression times of PCIA were (14.19±4.36) and (11.64±3.52) times, respectively; and the β-Endorphin (β -endorphin) 24 hours after the operation were (160.31±19.68) and (146.83±18.49) pg·mL-1, respectively; CC Chemokine ligand 2 (CCL2) were (109.39±19.78) and (97.86±17.88) pg·mL-1, respectively; angiotensin Ⅱ (Ang Ⅱ) were (79.14±12.53) and (70.65±11.71) pg·mL-1, respectively. The above indicators of treatment group were compared with those of control group, and the differences were all statistically significant (all P<0.05). The incidence rates of adverse reactions to anesthetic drugs during the perioperative period in the two groups of patients were 9.62%(5 cases/52 cases) and 16.00%(8 cases/50 cases), respectively, and there was no statistically significant difference (P>0.05).
The TLIP block with ropivacaine combined with betamethasone can enhance the analgesic effect during the perioperative period of patients undergoing PLIF, reduce the dosage of opioid drugs, alleviate early pain symptoms and the level of postoperative stress responses, and has a relatively high level of safety.
To investigate the changes of intestinal flora in patients with Helicobacter pylori (HP) positive gastric ulcer treated with rabeprazole capsule combined with aluminum phosphate gel based on metagenomics.
Patients with HP-positive gastric ulcers were selected who were admitted from January 2022 to December 2024. They were randomly divided into the combined group and the control group. The control group only received rabeprazole treatment, while the combined group received combined treatment with rabeprazole and aluminum phosphate gel. The model efficacy and key biomarkers for distinguishing patients in different treatment groups were detected using a linear kernel-based support vector classification (SVC) model and recursive feature elimination (RFE). The association between microbial abundance and clinical continuous indicators was detected using a support vector regression factor model (SVR). The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis was used to detect the metabolic and signaling pathways enriched by the differentially expressed genes in the intestinal microbiota. The clinical efficacy of the two groups was compared, and the safety was evaluated.
A total of 130 patients were enrolled in the study, with 65 patients in each of the combined group and the control group. The intestinal microbial diversity in the combined group was significantly higher than that in the control group (P<0.05). Using RFE to further distinguish between the two groups, the area under the curve (AUC) was 0.80. Among the patients in the combined group, the levels of 10 metabolites were elevated. Through multi-omics integrated analysis of the fecal samples of the two groups of patients, it was found that the AUC of combining specific microbial communities and fecal metabolites analysis was 0.85, with higher accuracy than using microbial community or metabolite analysis alone, and the statistical difference was statistically significant (P<0.05). SVC and SVR analysis showed that the intestinal inflammation of patients was related to the composition of specific microbial communities. A metabolic reaction network diagram was constructed based on KEGG. The results showed that the levels of arginase, protein phosphatase, and tyrosine phosphatase were higher in patients with positive HP gastric ulcers. The ulcer healing rates in the combined group and the control group were 95.38% (62 cases/65 cases) and 83.08% (54 cases/65 cases), respectively. There was statistically significant difference between the two groups (P<0.05). The incidence of adverse drug reactions was 10.77% (7 cases/65 cases) in the combined group and 16.92% (11 cases/65 cases) in the control group. There was no statistically significant difference between the two groups (P>0.05).
The treatment plan of rabeprazole combined with aluminum phosphate gel can enhance the diversity of intestinal microorganisms, promote the secretion of microbial metabolites, effectively improve the intestinal flora, and facilitate the recovery of patients.