Latest ArticlesTo evaluate the cost-utility of camrelizumab in combination with apatinib and sorafenib in the first-line treatment of advanced unresectable hepatocellular carcinoma(uHCC).
Based on the clinical trial data of CARES-310, a partitioned survival model was constructed to simulate the cost and outcomes of camrelizumab in combination with apatinib and sorafenib in the first-line treatment of advanced uHCC, and the incremental cost-effectiveness ratio(ICER)of the two strategies was calculated using the cost-utility analysis from the perspective of Chinese medical and health system. Single factor sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the stability of the results.
The total cost of camrelizumab in combination with apatinib regimen was 285 459 yuan, and 0.999 QALYs was obtained. The total cost of sorafenib regimen was 238 948 yuan, and 0.726 QALYs was obtained. The ICER of camrelizumab in combination with apatinib regimen against sorafenib regimen was 170 112 yuan·QALY-1, which did not exceed the willingness-to-pay threshold of 257 094 yuan·QALY-1 in China. The results of sensitivity analysis indicated that the basic analysis was robust.
From the perspective of Chinese healthcare system, camrelizumab combined with apatinib is cost-effectiveness compared with sorafenib in the first-line treatment of advanced uHCC.
To explore the regulation effect of hyperoside on renal ischemia-reperfusion(IR)injury and nuclear factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1)/quinone oxidoreductase 1(NQO1)signaling pathway in rats.
The models of renal IR rat were constructed by ligating bilateral renal arteries(60 minutes)and recovering perfusion(120 minutes). Forty SD rats were randomly divided into control group, model group and hyperoside 12.5, 25, 50 mg·kg-1 groups. The samples of blood and renal tissues were collected to detect levels of 24 h proteinuria,serum creatinine, blood urea nitrogen and superoxide dismutase(SOD), malondialdehyde(MDA). The renal tissue lesions were observed by HE staining. The expression of caspase-3 was detected by immunohistochemistry. The expression of inducible nitric oxide synthase(iNOS), interleukin(IL)-6 and IL-10 mRNA was detected by qRT-PCR. The expression of Bcl-2, Bax, Nrf2, HO-1 and NQO1 proteins in renal tissues was detected by Western blot. A total of 32 rats were randomly and averagely divided into control group, model group, hyperoside(50 mg·kg-1)group and hyperoside+ML385(30 mg·kg-1)group for relevant detection.
Compared with the model group, the levels of 24 h proteinuria, serum creatinine and blood urea nitrogen, and MDA were significantly decreased, while the levels of SOD were significantly increased in the hyperoside 25 and 50 mg·kg-1 groups(P<0.05). HE staining showed that there was obvious pathological injury of renal tissues and inflammatory cells infiltration was severe in the model group. The pathological injury were relieved in the hyperoside groups, and the improvement were more significant in the hyperoside 50 mg·kg-1 group. Compared with the model group, the expression of Bax/Bcl-2, caspase-3, iNOS and IL-6 mRNA were decreased significantly, while the expression of IL-10 mRNA, p-Nrf2/Nrf2, HO-1 and NQO1 and SOD were significantly upregulated in the hyperoside 25 and 50 mg·kg-1 groups(P<0.05). The expression of Bax/Bcl-2 decreased significantly in the hyperoside 12.5 mg·kg-1 group(P<0.05). ML385 can partially block the improvement effect of hyperoside on renal IR rats.
Hyperoside may inhibit apoptosis of renal cells, excessive oxidative stress and inflammatory response by up-regulating Nrf2/HO-1/NQO1 signaling pathways, and relieve renal IR injury.
To observe the effect of dexmedetomidine on the expression of NLR family CARD domain containing-3(NLRC3), a nucleotide oligomeric domain like receptor, in rats with ventilator-associated lung injury(VILI).
A total of 36 SD rats were randomly divided into normal control group, model group, and dexmedetomidine group(n=12 in each group). VILI model were made by mechanical ventilation with a ventilator. The dexmedetomidine group was intravenously injected with dexmedetomidine 5 μg·kg-1 at 20 minutes before VILI, then maintain a dose of 5 μg·kg-1·h-1. The normal control group and model group received continuous intravenous infusion of 0.5 mL·kg-1·h-1 of physiological saline. The pathological results of lung tissue in each group of rats were observed under the light microscope and the wet dry weight ratio of lung tissue was detected. Western blot and qRT-PCR were used to detect of protein and mRNA expression of NLRC3, NLR family pyrin domain containing 3 protein(NLRP3), apoptosis associated speck-like protein containing a CARD domain(ASC), caspase-1, and NF-κB p65. The protein level of IL-1β、IL-18 and IL-33 in serum were detected by ELISA.
Compared with the normal control group, severe pathological damage in the lung tissue were showed in the model group, the wet to dry weight ratio and IQA of lung tissue increased significantly(P<0.05).NLRC3 protein and mRNA expression in lung tissue down regulated(P<0.05), NLRP3, ASC, caspase-1, and NF-κB p65 protein and mRNA upregulated significantly(P<0.05), and the concentration of IL-1β、 IL-18 and IL-33 in serum increased significantly(P<0.05). Compared with the model group, the pathological damage of lung tissue in the dexmedetomidine group showed reduced, and the wet to dry weight ratio and IQA of lung tissue decreased(P<0.05), the expression of NLRC3 protein and mRNA in lung tissue increased significantly(P<0.05), NLRP3, ASC, caspase-1, and NF-κB p65 protein and mRNA downregulated(P<0.05), the concentrations of IL-1β, IL-18 and IL-33 reduced significantly(P<0.05).
Dexmedetomidine improves VILI in rats by upregulating the expression of NLRC3 in lung tissue, and its mechanism may be related to the inhibition of NLRP3 inflammasome activation.
Investigator-initiated-trial(IIT)is the most important part of clinical researches. Based on the IIT management practice of one 3A grade hospital in Beijing, this paper analyzed the organizational structure of clinical research,the key points of scientific review and ethical review, recordation filling, contract verification and quality control, which were compared with the IIT management measures issued by the NHC one by one. According to the above , this paper puts forward some corresponding countermeasures, aiming at improving the management level and promoting high-quality development of clinical research.
To investigate the anti-hepatic fibrosis effect of Qiwei Qinggan powder(QGS-7)through NF-κB signaling pathway in vivo and in vitro.
In vivo experiment, sixty male Wistar rats were randomly divided into 5 groups: blank group, CCl4 model group, QGS-7 low, medium, high dose groups. The blank group was gavaged with 0.5% CMC-Na solution daily, and the model group and each dose groups were gavaged with 50% CCl4 peanut oil solution twice a week,while each dose groups were gavaged with corresponding dose of QGS-7(135, 270, 405 mg·kg-1·d-1)for 8 weeks. The histopathological changes of liver were observed by HE and Masson staining. q-PCR and Western blot were used to detect the mRNA and protein expression of fibrosis markers of alpha smooth muscle actin(α-SMA), collagen and NF-κB signaling pathway-related factors. In vitro experiment, rats were gavage with QGS-7 1 350 mg·kg-1·d-1, and blood was taken after 7 d to prepare drug-containing serum, which was classified into the blank group, the LPS model group, and the QGS-7 drug-containing serum low-, medium- and high-concentration groups using HSC-T6 cells. Detection of apoptosis by double staining with Annexin V-FITC and PI. The mRNA and protein expression of α-SMA, collagen Ⅰ and NF-κB signaling pathway-related factors were detected by q-PCR and Western blot.
In vivo experiment, HE and Masson results showed that fibroblasts were increased of the tissues in the CCl4 model group, with disorganized cell arrangement and significant collagen deposition compared with the blank group. Compared with the blank group, α-SMA, collagen Ⅰ and NF-κBp65 protein and mRNA expressions of the liver tissues were significantly increased in the CCl4 model group(P < 0.05), and TLR4, p-TAK1,p-IKKα/IKKα, p-IKKβ/IKKβ, p-NF-κBp65/NF-κBp65 protein and mRNA expression were significantly increased(P < 0.05).Compared with the model group, the protein and mRNA expression of the above factors were significantly decreased in each dose group of QGS-7(P < 0.05). In vitro experiments, the apoptosis rate was lower in both the blank group and the LPS model group. Compared with the model group, the apoptosis rate was significantly increased in each concentration of the QGS-7-containing serum group(P < 0.01), and the mRNA and protein expression of the α-SMA, collagen Ⅰ, and the NF-κB signalling pathway related to factors were consistent with the trend in vivo experimental expression.
QGS-7 has good anti-fibrotic effects, and the mechanism may through down-regulation of key targets of NF-κB signaling pathway to exert anti-fibrotic effects.
To clarify antitumor pharmacological mechanism of natural compound tryptanthrin by network pharmacology.
The drug-likeness of tryptanthrin molecule was evaluated through ADMETlab 2.0 database,the action targets of tryptanthrin were predicted through PharmMapper and Swiss TargetPrediction database, tumor disease targets were collected by OMIM and DisGeNET database, the potential protein targets of antitumor action of tryptanthrin were then screened out. Using STRING database and Cytoscape 3.7 to sequentially construct protein-protein interaction(PPI)networks and compound target pathway disease networks between protein targets. The GO functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID database. AutoDock Vina 1.1.2 as a molecular docking method was used to analyze the interaction between tryptanthrin and the selected core target proteins. The gene expression profiling interactive analysis of the core targets was conducted with the existing clinical tumor database.
A total of 158 antitumor core targets of tryptanthrin were obtained by network pharmacological study, the biological processes of GO functional enrichment analysis had an association with inflammatory response, protein phosphorylation and intracellular signal transduction, etc. The cellular components were relatively close to cytosol, cytoplasm and macromolecular complex,etc. The molecular functions were associated with MAP kinase activity, ATP binding and enzyme binding, etc. The results of KEGG pathway enrichment analysis showed that pathways in cancer, PI3K-AKT signaling pathway, etc were the main pathway that tryptanthrin exerted its antitumor effect, it involved the core targets such as AKT1, PI3K, MAPK1, HSP90AA1,JAK2, NFKB1. The 5 core targets including AKT1, HSP90AA1, PI3K, JAK2, MAPK1 had good binding activities with tryptanthrin, all binding energy were less than -8.6 kcal·mol-1. The results of gene expression profiling interactive analysis of the core targets showed that all five core protein targets played important roles in occurrence and development of human tumor diseases.
Tryptanthrin exerted its anti-tumor effect through PI3K-AKT signaling pathway and others.
To evaluate the safety and efficacy of dronedarone in the blanking period in patients underwent atrial fibrillation catheter ablation in the real-world.
A total of 150 patients with atrial fibrillation who underwent catheter ablation at co-operative centers between May 1st, 2021 and December 31st, 2021 were included. During the blanking period, the patients were given oral dronedarone(400 mg, morning and evening)for 3 months. At 3 months ± 14 days after surgery, the patients were followed up, and 24-hour Holter, transthoracic echocardiography, liver function and renal function were reviewed. The adverse events occurred during the follow-up were recorded.
Compared with before surgery,there were no significant differences in heart rate, PR interval, and left ventricular ejection fraction were observed at 3 months after surgery, while QTc interval increased((434.0±29.2)ms vs.(443.5±31.8)ms, P=0.017)). Left atrial diameter((40.6±6.5)mm vs.(38.4±6.0)mm, P=0.007))and lower left ventricular end-diastolic diameter((47.9±4.3)mm vs.(46.4±5.1)mm, P=0.012))decreased. Six patients discontinued in the blanking period(included high atrioventricular block in 1 patient, significant bradycardia in 2 patients, significant prolongation of the QTc interval in 1 patient, and digestive system symptoms in 2 patients). There were no composite endpoints of cardiovascular death, heart failure or rehospitalization associated with antiarrhythmic drugs. At follow-up of 3 months, the rate of sinus rhythm maintenance was 85.3%(128/150).
Dronedarone is safe and effective in the blanking period for patients underwent atrial fibrillation catheter ablation. Moreover, it’s good in adherence.
To visually analyze the research hotspots and trends of Sparganii Rhizoma in the past 10 years based on the knowledge mapping method to provide references for future research in this field.
The research on Sparganii Rhizoma from January 1st, 2012 to January 1st, 2022 were selected from CNKI, and the sample literature included in the study was analyzed using CiteSpace software, and the annual publication volume, author collaboration network,institutional collaboration network, keyword co-occurrences, keyword clustering, and keyword emergent mapping were drawn.
A total of 592 papers were included, and the annual publication volume was relatively stable. The team represented by SHI HY, HOU RJ and LIANG QL was formed, and there was less cooperation among institutions. The keywords with higher frequency include data mining, medication law, Sparganii Rhizoma, etc., forming 10 clusters. The research hotspots mainly focus on gynecological diseases and tumors, clinical research, mechanism of action, etc. The keyword emergence analysis obtained a total of 43 emergent words, with more research on data mining, clinical research, and treatment of tumors and gynecological diseases, and the laboratory research pays more attention to the extraction of the active ingredient and its active ingredients and the mechanism of action. Laboratory studies paid more attention to the extraction of active ingredients and their active components.
In recent years, the research hotspots of Sparganii Rhizoma mainly focuses on the clinical medication for gynecological and oncological diseases, and gradually extends to the treatment of refractory diseases such as organ fibrosis. In the future, the research direction of Sparganii Rhizoma will tend to be more towards the research of the target mechanism and the summary of the law of medication.
Cyclopofol is a new type of intravenous anesthesia drug, with drug characteristics similar to propofol.At present, multiple clinical trials have confirmed that cyclopofol has the characteristics of fast onset and recovery, and can be used for general anesthesia induction, painless gastroscopy, fiberoptic bronchoscopy, etc. It has certain advantages in the application of intensive care units and elderly patients. The safety of cyclopofol is relatively high, and the incidence of injection pain caused by cyclopofol is significantly lower than that of propofol. With the gradual application of cyclopofol in clinical practice, its scope of application, mechanism of action, and advantages are worthy of further research.