Latest ArticlesAIM To analyze the effects of different doses of ciprofol on general anesthesia induction in elderly patients, and the influence on hemodynamics during general anesthesia induction. METHODS One hundred and twenty elderly patients undergoing elective surgery were randomly included in ciprofol 0.2 mg·kg-1 group (C0.2 group), ciprofol 0.3 mg·kg-1 group (C0.3 group) and ciprofol 0.4 mg·kg-1 group (C0.4 group), with 40 cases in each group. The corresponding dose of ciprofol was injected intravenously according to the group, and the injection time was 30 s. And all patients induced by rocuronium 0.6 mg·kg-1 and sufentanil 0.5 μg·kg-1 were injected intravenously, followed by ciprofol 0.8-2.4 mg·kg-1·h-1, remifentanil 8-15 μg·kg-1·h-1 was injected intravenously and 1% sevoflurane was inhaled for anesthesia maintenance. The bispectral index (BIS) was maintained 40~60 during the operation. The mean arterial pressure (MAP), heart rate (HR) and BIS of the patients were monitored, the success rate of anesthesia induction, the number of cases of remedial sedation and the time of loss of consciousness were recorded, and the occurrence of adverse reactions were observed. RESULTS The MAP, HR and BIS of the three groups immediately after anesthesia induction (T1), 10 s after tracheal intubation (T2) and 3 min after tracheal intubation (T3) were significantly lower than those of the same group at the time of entering the operating room (P<0.05), and the MAP and HR of T1-T3 in the C0.4 group were significantly lower than those in the C0.2 group and C0.3 groups (P<0.05). There were no significant differences in MAP and HR of T1-T3 between the C0.3 group and C0.2 group (P>0.05). There were no significant differences in the success rate of anesthesia induction among the three groups (P>0.05). The rate of remedial sedation in the C0.2 group was significantly higher than that in the C0.3 group and C0.4 group (P<0.05), and the time of consciousness loss was significantly longer than that in the C0.3 group and C0.4 group (P<0.05). There was no significant difference in rate of remedial sedation and consciousness loss time between the C0.3 group and C0.4 group (P>0.05). The incidence of hypotension and bradycardia in the C0.4 group was significantly higher than that in the C0.2 group and C0.3 group (P<0.05), but there was no significant difference in the incidence of hypotension and bradycardia between the C0.3 group and C0.2 group (P>0.05). CONCLUSION Ciprofol 0.3 mg·kg-1 has good safety and efficacy for general anesthesia induction in elderly patients.
AIM To investigate the effects of salidroside ( Sal) on the proliferation, migration and collagen synthesis of human keloid fibroblasts ( HKF) by regulating Notch1/Hes1 pathway. METHODS HKF in logarithmic growth period was divided into control group ( NC group), Sal-L, Sal-M, Sal-H ( 10, 20, 40 μmol·L-1) group, Jagged1 group (Notch activator,5 mg·L-1), Sal ( 40 μmol·L-1) + Jagged1 (5 mg·L-1) group. MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were detected by flow cytometry. Cell migration was detected by scratch test, and Western blot was used to detect the expression of collagen-Ⅰ, collagen-Ⅲ, proliferating cell nuclear antigen ( PCNA), matrix metalloproteinase-2 (MMP-2), Notch1 and Hes1 proteins. RESULTS Compared with the NC group, the A value, the proportion of cells in S phase and G2/M phase decreased, scratch healing rate decreased, the protein expression of collagen-Ⅰ, collagen-Ⅲ, PCNA, MMP-2, Notch1 and Hes1 decreased in the Sal-L, Sal-M and Sal-H group, the proportion of cells in G0/G1 phase and the rate of apoptosis increased, in a dose-dependent manner ( P<0.05), while the Jagged1 group showed the opposite change of the above indexes. Compared with the Sal-H group, the A value, the proportion of cells in S phase and G2/M phase, scratch healing rate, the protein expression of collagen-Ⅰ, collagen-Ⅲ, PCNA, MMP-2, Notch1 and Hes1 increased, the proportion of cells in G0/G1 phase and the rate of apoptosis decreased in the Sal group ( P<0.05). CONCLUSION Sal may inhibit the proliferation, migration and collagen synthesis of HKF by inhibiting Notch1/Hes1 pathway.
AIM To evaluate the effectiveness, safety and economy of lorlatinib in anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients, and provide evidence for clinical treatment. METHODS Databases such as PubMed, Cochrane Library, CNKI, Wanfang Data, and VIP and Health Technology Assessment (HTA) related websites were searched to collect HTA reports, systematic evaluation/meta-analysis and pharmacoeconomic evaluation of loratinib for ALK positive NSCLC. Select the literature according to the inclusion and exclusion criteria, extract the data, and evaluate the literature quality. Qualitative description was performed. RESULTS A total of 16 literatures were included, involving 11 systematic review/meta-analysis and 5 pharmacoeconomic evaluation. In terms of effectiveness，compared with other ALK-tyrosine kinase inhibitors (TKIs) and chemotherapy as first-line treatment, lorlatinib significantly prolonged the progression free survival (PFS) in ALK positive NSCLC patients. Compared with chemotherapy as a second- or third-line treatment, lorlatinib significantly prolonged PFS and overall survival. In terms of safety, there was no statistical difference among the ALK-TKIs and chemotherapy in the incidence of adverse events (AEs) of grade≥3, but the incidence of lorlatinib was relatively high. In regards to the serious AEs and AEs leading to treatment discontinuation, lorlatinib was the lowest. In terms of economy, lorlatinib was not cost-effectiveness compared to ensartinib and crizotinib in China, but lorlatinib was cost-effectiveness compared to chemotherapy as a second- or third-line treatment in Greece and Sweden. CONCLUSION Lorlatinib shows good efficacy and safety for ALK positive NSCLC, but its cost-effectiveness after price reduction in China needs further evaluation.
To study the anti-tumor effect of icotinib combined with metformin on non-small cell lung cancer （NSCLC） H1975 cells and its possible mechanism.
CCK-8 assay was used to detect the proliferation inhibitory effect and combination index （CI） of icotinib monotherapy （0, 0.1, 1, 5, 10, 20, 40 μmol·mL-1）, metformin monotherapy （0, 2, 4, 8, 16, 32, 64 mmol·mL-1）, and icotinib （0, 0.125, 0.25, 0.5, 1 times of IC50） combined with metformin （0.5 times of IC50） on the H1975 cells. The migratory ability of the cells was detected by scratch test，and the invasive ability of the cells was detected by invasion test. Annexin V-FITC/PI flow cytometry was used to detect the rate of apoptosis. Western blot was used to detect the expression level of related proteins.
The IC50 of icotinib and metformin for the inhibition on H1975 cells after 48 h were （49.90±4.84） μmol·mL-1 and （13.20±1.27）mmol·mL-1, respectively. Icotinib and metformin produced a synergistic effect in H1975 cells（CI<1）. Compared with the metformin group and the icotinib group, the migration rate and invasion ability of combination group were significantly decreased, and the apoptosis rate was significantly increased （P<0.05）；the expression of p-Akt, p-mTOR and Bcl-2 were significantly decreased, while the expression of p-AMPK and Bax were significantly increased （P<0.05）.
Icotinib and metformin have significant synergic antitumor effects and proapoptotic effects on non-small cell lung cancer H1975 cells, and the underlying mechanism may be related to enhancing activation of AMPK and inhibition of Akt/mTOR signaling pathway.
Glaucoma, a leading cause of irreversible blindness worldwide, primarily involves pathological elevation of intraocular pressure （IOP）, which is its main risk factor, so the clinical goal in treating glaucoma is to reduce IOP to individual target levels. Currently, the classical local anti-glaucoma drugs include five categories: prostaglandin analogues（PGAs）, β-adrenergic receptor blockers, α2- adrenergic receptor agonists, carbonic anhydrase inhibitors, and cholinergic receptor agonists. These drugs mainly work by reducing aqueous humor production, increasing aqueous outflow through the trabecular pathway and the uveal scleral pathway, and contracting the pupil sphincter to open the chamber angle. Among these, PGAs have become the preferred choice for controlling IOP in primary open-angle glaucoma patients due to their efficacy and safety. In recent years, the introduction of novel glaucoma medications, including Rho kinase inhibitors and nitric oxide-donating anti-glaucoma drugs, along with the development of related drug-releasing formulations （intraocular and extraocular drug delivery systems）, offers new options for glaucoma treatment.
To study the antibacterial mechanism of palmatine based on network pharmacology, molecular docking, and molecular dynamics.
The drug targets of palmatine were predicted through the Swiss Target Prediction website, and the potential antibacterial targets of palmatine were obtained by mapping them with the antibacterial targets retrieved from GeneCards and OMIM databases. Protein-protein interaction network was constructed using STRING database and Cytoscape software and key targets were screened. The DAVID database was used to carry out Gene Ontology（GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of potential targets, and visual processing was performed to build the “Component-Target-Pathway” network of palmatine. The binding of palmatine to key targets was validated through molecular docking and molecular dynamics simulations. In vitro antibacterial experiments were conducted to verify the antibacterial activity of palmatine.
A total of 28 critical anti-bacterial targets of palmatine were screened and enriched to 199 GO entries and 105 related pathways. “Ingredients-Target-Pathway”network showed that MAPK8, RAC1, and STAT3 were key anti-bacterial targets.The molecular docking results indicated that palmatine had an excellent binding effect with key targets MAPK8 and RAC1. Molecular dynamics studies found that there were hydrogen bonds and hydrophobic interactions between palmatine and proteins, enabling stable binding of palmatine to target proteins. In vitro antibacterial experiments showed that palmatine had strong inhibitory activity against Staphylococcus aureus and Candida albicans, and it had synergistic effects when combined with positive drugs.
Palmatine may exert its antibacterial effects by inhibiting the gene expression of MAPK8 and RAC1 through endocrine resistance and signaling pathways such as PI3K-Akt and FoxO.
To analyze the general patterns and characteristics of osimertinib related interstitial lung disease（ILD）.
The case reports of osimertinib related ILD from CNKI, VIP, Wanfang and PubMed database between November 2015 to June 2023 were searched and analyzed.
A total of 25 case reports were enrolled,involving 28 cases with ILD, 14 male and 14 female cases, aged 32 to 86 years old. PD-1 inhibitors were used sequentially in 4 patients before administering osimertinib, 21 patients developed ILD in 3 months, 25 patients experienced symptom relief after discontinuation reduction medication, and 3 patients died.
ILD should be closely guarded in 3 months of the application of osimertinib, especially these patients who received the sequence treatment of PD-1 inhibitors.The key to improving the prognosis is to stop using osimertinib immediately after ILD.
To observe the difference of clinical efficacy and safety between regular hemodialysis （HD）and peritoneal dialysis （PD） uremic patients treated with roxadustat for renal anemia.
From December 2019 to March 2023, 102 renal anemia patients treated with roxadustat for uremic dialysis were selected. The initial dose of roxadustat was chosen based on weight, with 100 mg orally for patients weighing 45 to 60 kg and 120 mg for those weighing ≥60 kg. The medication was administered three times a week for 12 consecutive weeks, with dosage adjustments according to hemoglobin （Hb） levels. According to the dialysis method, there were 50 cases in the PD group and 52 cases in the HD group. Within the groups, those with high sensitive C-reactive protein （hs-CRP） ≥6 mg·L-1 were classified as high hs-CRP subgroup, while those with <6 mg·L-1 were considered the normal hs-CRP subgroup.Changes in anemia-related indicators, iron metabolism, lipid metabolism, and adverse reactions before and after roxadustat treatment were observed in both groups.
After 12 weeks of treatment with roxadustat, the levels of Hb, red blood cell count （RBC）, hematocrit （HCT）, and serum iron （SI） in the both groups all increased compared with before the treatment （P<0.05）, while the levels of serum ferritin （SF）, total cholesterol （TC）,triglyceride （TG）, and low-density lipoprotein cholesterol （LDL-C） all decreased （P<0.05）. After treatment, the levels of Hb, RBC, HCT, SI, TC, and LDL-C in the PD group were significantly higher than those in the HD group（P<0.05）. There were no significant differences in transferrin saturation （TSAT）, total iron-binding capacity （TIBC）,and high-density lipoprotein cholesterol （HDL-C） levels within and between the groups before and after the treatment（P>0.05）. There were no significant differences in TG and SF levels and the occurrence of adverse reactions between the two groups （P>0.05）. After 12 weeks of treatment, the average Hb level of the high hs-CRP subgroup and normal hs-CRP subgroup of the two groups significantly increased compared with before treatment （P<0.05）, and there was no significant difference between the two subgroups （P>0.05）.
Roxadustat is effective in improving renal anemia in uremia patients with HD or PD, and the short-term safety is good. Compared with HD patients, anemia is more significantly improved in PD patients.
To observe the anesthetic effect of ciprofol in intracranial aneurysm embolization.
One hundred and twenty patients undergoing intracranial aneurysm embolization, ASA Ⅰor Ⅱ, were randomly divided into control group and experimental group （n=60, each group）. During anesthesia induction, patients were given with midazolam 0.04 mg·kg-1, sufentanil 0.25 μg·kg-1, ciprofol 0.4 mg·kg-1 （experimental group） or propofol 2.0 mg·kg-1 （control group）, and rocuronium 0.6 mg·kg-1. During anesthesia maintenance, all patients were maintained with remifentanil 1 μg·kg-1·h-1 and cisatracurium 0.1 mg·kg-1·h-1, combined with ciprofol 0.8 mg·kg-1·h-1 （experimental group） or propofol 5 mg·kg-1·h-1 （control group）. The bispectral index （BIS） was maintained between 40 and 60 by adjusting the pumping speed during the operation. The changes of vital signs and BIS were observed. The anesthesia induction time,awakening time, and Ramsay sedation score after extubation were recorded. And the occurrence of adverse reactions was also observed.
There was no significant difference in systolic blood pressure （SBP）, diastolic blood pressure （DBP）,and heart rate （HR） between the two groups before anesthesia, after anesthesia induction, after tracheal intubation, at the end of operation, and after tracheal extubation. The BIS at the end of operation in the experimental group was lower than that in the control group （P<0.05）. The fluctuation value of SBP, DBP, and HR during anesthesia induction in the control group was significantly greater than that in the experimental group （P<0.05）. The recovery time of the experimental group was slightly longer while the use of sedatives was less than that of the control group （P<0.05）. The incidences of post-induced hypotension, hypertension after intubation, and injection pain in the experimental group were lower than those in the control group （P<0.05）.
Ciprofol can be used in intracranial aneurysm embolization with outstanding sedative efficacy. The hemodynamics of patient is more stable, and the incidence of postoperative adverse reaction is low.
Risk minimisation measure （RMM） is a critical step to maximize the benefit-risk ratio of a medicinal product in pharmacovigilance activities. Through literature review and consulting the websites of major healthcare authorities in Europe Union, the USA, and Japan, this paper reviewed the RMM regulatory requirements and implementation status of these countries and regions. It was found that Europe, the USA, and Japan established relevant regulations earlier and accumulated valuable experience, and the specific implementation and supervision intensity of RMM varied among regions due to differences in medical systems. For example, additional risk minimization measures in Japan and the European Union are presented as risk evaluation and mitigation strategies in the USA. It is suggested that RMM-related regulations and supervision system should be continuously improved, and the marketing authorization holders in China should develop RMM implementation plans that conform to the actual conditions of China based on foreign experience and combined with the current situation of local medical system, and conduct feasible and efficient RMM effectiveness assessment to ensure patient medication safety.
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