摘要:OBJECTIVETo provide reference for the regulation of electronic prescription circulation under the mode of “medical science + pharmacy”.METHODSBased on evolutionary game theory, a tripartite evolutionary game model was constructed for related parties of electronic prescription circulation (government agencies, internet hospitals and third-party drug platforms) under the mode of “medical science + pharmacy”. The influential factors of the three parties’ strategy selection were analyzed and verified by simulation. RESULTS &CONCLUSIONSThe strategic choices of all parties in the game were affected by the other two parties. Reducing the cost of strict supervision or increasing the punishment for the other two parties would increase the probability of strict supervision of government agencies. Enhancing reputation losses, increasing penalties, and reducing the cost difference when choosing different strategies would have regulatory and binding effects on internet hospitals and third-party drug platforms. It is suggested that government agencies can introduce diversified supervision mode and establish an integrated “intelligent supervision + traceability” system; pay attention to the construction of reputation mechanism, and promote the coordinated linkage of all parties; increase the punishment for violations, provide policy support, reduce the cost of compliance behavior to promote the high-quality development of electronic prescription circulation under the mode of “medical science + pharmacy”.
关键词:evolutionary game;prescription regulation;internet hospital;third-party drug platforms
摘要:OBJECTIVETo study the improving mechanism of Buyang huanwu decoction (BYHW) on idiopathic pulmonary fibrosis (IPF) model rats.METHODSNinety-six Wistar rats were randomly divided into blank group, model group, positive control group, and BYHW low-dose, middle-dose and high-dose groups, with 16 rats in each group. Except for the blank group, the IPF model was induced in other groups by intratracheal instillation of bleomycin (5 mg/kg). Starting from the day of modeling, the blank group and model group were given normal saline (10 mL/kg) intragastrically, while the rats in the positive control group were given dexamethasone solution (5 mg/kg) intragastrically, BYHW low-dose, middle-dose and high-dose groups were treated with BYHW (2.5, 5, 10 g/kg, by crude drug) intragastrically, once a day, for 28 consecutive days. The body mass of rats in each group was measured on days 0, 7, 14, 21 and 28 after modeling. The number of adherent white blood cells in pulmonary veins was observed by a dynamic visualization system. The contents of TNF-α and IL-6 in serum and TNF-α, IL-6, HYP and TGF-β1 in lung tissue were detected; the protein expression of ZO-1 was also detected. The pathomorphological changes in lung tissue were observed.RESULTSCompared with the model group, the body weight of rats all increased significantly in BYHW high-dose and middle-dose groups, positive control group, while the number of adherent white blood cells in pulmonary veins was decreased significantly; the contents of TNF-α (except for serum in BYHW middle-dose group) and IL-6 in serum and lung tissue, the contents of HYP and TGF-β1 in lung tissue were decreased significantly, while the protein expression of ZO-1 in the lung tissue was increased significantly (P<0.05 or P<0.01). The pathological changes of lung tissue were improved to varying degrees.CONCLUSIONSBYHW may play anti-pulmonary fibrosis role by improving leukocyte adhesion, anti-inflammatory, anti-fibrosis, and other aspects of pulmonary microcirculation.
摘要:OBJECTIVETo extract the effective components of Psoralea corylifolia and evaluate its efficacy in the treatment of vitiligo.METHODSThe concentrations of psoralen, isopsoralen, neobavaisoflavone, corylin, psoralidin, corylifolinin, and bakuchiol in P. corylifolia extract were determined by ultra-performance liquid chromatography. Based on the analytic hierarchy process (AHP) and Plackett-Burman design, with the concentrations of the 7 components as evaluation indexes and the crushing degree, ethanol concentration, and soaking time as factors, the extraction process of P. corylifolia was optimized by Box-Behnken response surface methodology and the validation test was conducted. Zebrafish were divided into blank control group, positive control group (8-methoxypsoralen, 10.8 μg/mL), and low-, medium-, and high-concentration groups of P. corylifolia extract (500, 1 000, 2 000 μg/mL), with 6 fish in each group. The effects of P. corylifolia extract on the melanin production of zebrafish were studied by density analysis.RESULTSThe best extraction process was P. corylifolia powder over 60 meshes and soaked in 80% ethanol for 72 hours. The average comprehensive score of three validation experiments was 98.27, with an RSD of 1.36%, and the relative error was 1.02% compared with the predicted value of the fitting equation (97.28). Compared with the blank control group, the melanin pigmentation of zebrafish in the low-, medium-, and high-concentration groups of P. corylifolia extract was significantly increased (P<0.01).CONCLUSIONSThe optimized extraction process of P. corylifolia is reasonable and feasible, and the obtained P. corylifolia extract can significantly promote the production of melanin in zebrafish.
摘要:OBJECTIVETo explore the intestinal absorption characteristics of saikosaponins.METHODSBased on everted intestinal sac model, using accumulative absorption amount (Q) and absorption rate constant (Ka) as indexes, UHPLC-MS/MS technique as a method, the absorption of saikosaponin A, B2, C, D and F from total saponins of Bupleurum chinense (8 g/mL, by crude drug) in the duodenum, jejunum and ileum was detected.RESULTSThe correlation coefficients (r) of the regression equations for the absorption of saikosaponins A, B2, C and F in the duodenum, jejunum and ileum were all higher than 0.95, while the r of saikosaponin D in the above intestinal segments was lower than 0.95; compared with the absorption of the same composition in the duodenum, the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min, as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased (P<0.05).CONCLUSIONSSaikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum, jejunum and ileum; among them, saikosaponin A, B2, C and F are linearly absorbed, which conforms to the zero-order absorption characteristics, but saikosaponin D shows non-linear absorption.
摘要:OBJECTIVETo investigate the effects of polyphyllin Ⅵ(PPⅥ) on the proliferation and apoptosis of glioma cells and potential mechanism.METHODSUsing human glioma LN229 cells as objects, MTT assay was used to detect the survival rate after treated with different concentrations of PPⅥ [0 (control group), 1, 2, 4, 8, 16, 32, 64 μmol/L] for different time (24, 48, 72 h). The clone formation experiments were adopted to detect the number of cell clones and clone formation rate after being treated with different concentrations of PPⅥ [0 (control group), 2, 4, 8 μmol/L] for 14 days. The flow cytometry and Western blot assay were used to detect the apoptotic rate of cells, the expressions of apoptosis-related protein [B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved caspase-3], and the expressions of related proteins of Fas/Fas ligand (FasL) death receptor pathway and protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) pathway after being treated with different concentrations of PPⅥ [0(control group), 4, 8 μmol/L] for 24 h.RESULTSCompared with the control group, the survival rate of cells, the number of clones and clone formation rate, the protein expression of Bcl-2, and the phosphorylation levels of Akt and GSK-3β protein were decreased significantly in different concentration groups of PPⅥ (P<0.05 or P<0.01). The apoptotic rate, the protein expressions of Bax, cleaved caspase-3, Fas, FasL and cleaved caspase-8 were increased significantly (P<0.05 or P<0.01).CONCLUSIONSPPⅥ can inhibit the proliferation and induce the apoptosis of human glioma LN229 cells, which may be related to the activation of the Fas/FasL death receptor pathway and the inhibition of the Akt/GSK-3β pathway.
关键词:human glioma cell;proliferation;apoptosis;Fas/FasL death receptor pathway;Akt/GSK-3β pathway
摘要:OBJECTIVETo investigate the effects and mechanism of curcumin (Cur) solid lipid nanoparticles (SLN) loaded with flower-shaped lactose (Cur-SLN-FL) for lung inhalation on lung inflammation in chronic obstructive pulmonary disease (COPD) model mice.METHODSFirstly, the irritation of Cur-SLN-FL to lung tissue was investigated, and the local safety of inhalation materials was determined. Then, 10 mice were randomly selected and injected with normal saline through the trachea, and the other 50 mice were all injected with porcine trypsin solution (concentration of 33.3 mg/mL, dosage of 1.0 mL/kg) to induce the COPD model. After normal feeding for 28 days, the mice were divided into sham operation group, model group, budesonide group (20 mg/kg), Cur-SLN-FL high-dose and low-dose groups (100, 50 mg/kg), with 10 mice in each group. The corresponding drugs were given to each group, once a day, for 14 consecutive days. Twenty-four hours after the last administration, the bronchoalveolar lavage fluid (BALF) of mice in each group was collected and the differential count of white blood cells was determined. Hematoxylin-eosin (HE) staining was used to observe the histopathology of the trachea and lung tissue in each group. Masson staining was used to detect collagen deposition in the lung tissue of mice in each group. Immunohistochemical method was used to detect the positive expressions of nucleotide-binding oligomerization domains-like receptor protein-3 (NLRP3), caspase-1 and interleukin-1β (IL-1β) in lung tissue of mice. Western blot assay was used to detect the protein expressions of NLRP3, caspase-1 and nuclear factor of kappa B(NF-κB) in lung tissue.RESULTSCur-SLN-FL had no obvious pulmonary irritation. Compared with the sham operation group, the total number of white blood cells, neutrophils and eosinophils in BALF of the model group increased significantly, while the number of lymphocytes decreased significantly (P<0.05); ciliated columnar epithelium proliferated, thickened and exfoliated in the trachea, mucus accumulated in the cavity and interstitial inflammatory cells infiltrated in the lung tissue; the deposition of collagen fibers in lung tissue increased significantly, the positive expressions of NLRP3, caspase-1 and IL-1β in lung tissue increased significantly, and the expressions of NLRP3, caspase-1 and NF-κB protein in lung tissue all increased significantly (P<0.05). After giving Cur-SLN-FL, the above indexes were all improved to certain extent.CONCLUSIONSCur-SLN-FL can improve the pulmonary inflammatory reaction in COPD model mice, and its mechanism may be through regulating the NLRP3 signaling pathway, inhibiting the expressions of caspase-1, NF-κB and IL-1β, thus alleviating the process of pulmonary fibrosis in COPD model mice.
摘要:OBJECTIVETo investigate the influence of Huayu xiaozhong decoction (HXD) on inflammatory response in rats with deep vein thrombosis (DVT).METHODSThe male SD rats were divided into control group (CK group), model group (Model group), HXD low-dose group (HXD-L group, HXD 10.86 mg/kg), HXD medium-dose group (HXD-M group, HXD 21.71 mg/kg), HXD high-dose group (HXD-H group, HXD 32.57 mg/kg), positive control group (LMWHS group, low molecular weight heparin sodium 600 IU/kg), silent information regulator 2 (SIRT2) inhibitor group (AK-7 group, AK-7 20 mg/kg), HXD-M+AK-7 group (HXD 21.71 mg/kg+AK-7 20 mg/kg), with 12 rats in each group. Except for the CK group, the DVT rat was induced by the Reyers method in other groups; after modeling, administration groups were given relevant medicine intragastrically/intraperitoneally, once a day, for consecutive 2 weeks. Twenty-four hours after the last medication, the coagulation function indexes [activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), fibrinogen (FIB)] and inflammatory indexes in serum and inferior vena cava tissue [interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)] of rats were detected. The formation of thrombus was observed, and the wet and dry masses of the thrombus were weighed. The protein expressions of tissue factor (TF) and SIRT2 as well as the phosphorylation and acetylation levels of nuclear factor kappa B (NF-κB) p65 in inferior vena cava tissue were detected.RESULTSCompared with CK group, APTT, TT and PT of rats in Model group were shortened significantly(P<0.05); the content of FIB, the levels of IL-1β, IL-6 and TNF-α, wet weight and dry weight of venous thrombus, TF protein staining score, the phosphorylation and acetylation levels of NF-κB p65 protein increased significantly (P<0.05); the inferior vena cava was full of thrombus, and the protein expression of SIRT2 decreased (P<0.05). Compared with Model group, above indexes of HXD-L group, HXD-M group, HXD-H group and LMWHS group were improved, while the improvement effects of HXD-M group, HXD-H group and LMWHS group were significantly better than those of HXD-L group (P<0.05). The trends of the corresponding indicators in AK-7 group were opposite to the above (P<0.05); AK-7 attenuated the inhibitory effect of medium-dose HXD on the inflammatory response in model rats (P<0.05).CONCLUSIONSHXD may inhibit the inflammatory response of DVT rats by activating SIRT2/NF-κB signaling pathway.
关键词:deep vein thrombosis;inflammatory response;silent information regulator 2/nuclear transcription factor kappa B signaling pathway
摘要:OBJECTIVETo establish a quantitative analysis of multi-components by single marker (QAMS) method for simultaneous determination of 10 ganoderic acids in Ganoderma lucidum.METHODSUsing ganoderic acid A as internal reference, high-performance liquid chromatography (HPLC) method was adopted to calculate relative correction factors of the other 9 components, such as ganoderic acid B, ganoderic acid C2, ganoderic acid D, ganoderic acid F, ganoderic acid H, ganoderenic acid A, ganoderenic acid B, ganoderenic acid C, ganoderenic acid D; the contents of above ganoderic acids were calculated with relative correction factors, and compared with the results of external standard method.RESULTSThe linear relationship of ganoderic acid A, ganoderic acid B, ganoderic acid C2, ganoderic acid D, ganoderic acid F, ganoderic acid H, ganoderenic acid A, ganoderenic acid B, ganoderenic acid C and ganoderenic acid D were 0.032-3.996, 0.040-4.971, 0.037-4.568, 0.028-3.558, 0.033-4.177, 0.044-5.440, 0.032-3.944, 0.040-4.994, 0.045-5.593 and 0.035-4.342 mg/mL (all R 2≥0.999 2), respectively. RSDs of precision, stability (24 h) and reproducibility tests were all lower than 2%. Their average recovery rates were 99.43%, 100.25%, 98.50%, 99.88%, 100.59%, 99.64%, 98.50%, 99.40%, 99.64% and 99.76%, respectively (RSD<2%, n=6). Relative correction factors of ganoderic acid B, ganoderic acid C2, ganoderic acid D, ganoderic acid F, ganoderic acid H, ganoderenic acid A, ganoderenic acid B, ganoderenic acid C and ganoderenic acid D were 1.788 5, 1.288 2, 1.126 4, 1.698 5, 0.885 4, 5.468 1, 4.210 9, 5.780 8, 4.290 3, respectively. Relative errors between the content obtained by QAMS method and external standard method for G. lucidum from different origins were within ±12%.CONCLUSIONSIt is feasible that the contents of 10 ganoderic acids are determined simultaneously by QAMS method, using ganoderic acid A as internal reference. This method shows good precision and reproducibility and can be used for the quality control of G. lucidum.
关键词:Ganoderma lucidum;quantitative analysis of multi-components by single marker;relative correction factor
摘要:OBJECTIVETo explore the mechanism of Taohong siwu decoction (THD) improving peripheral nerve injury induced by paclitaxel (PTX) in rats.METHODSThe effects of THD (1 g/mL drug-containing serum) and PTX (0.1 μmol/L) alone or in combination on the proliferation rate of Schwann cells line RSC96 as well as the expressions of lysosomal-associated membrane protein-2 (LAMP2), autophagy marker protein yeast Atg 6 homolog (Beclin1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) were investigated, and then compared with autophagy promoter rapamycin and autophagy inhibitor 3-methyladenine (3-MA). The effects of high-dose and low-dose THD on the expressions of myelin basic protein (MBP) and myelin protein zero (MPZ), S100 calcium-binding protein (S100), LAMP2, Beclin1, PI3K, Akt and mTOR were tested at the end of the experiment.RESULTSAfter treatment of THD+PTX, the proliferation rate of RSC96 cells was significantly higher than those treated with PTX alone. After treatment of THD+PTX or THD+3-MA, the protein expressions of LAMP2 and Beclin1 in RSC96 cells were significantly higher than those treated with PTX or 3-MA alone, while the protein expressions of PI3K, Akt and mTOR were significantly lower than those treated with PTX or 3-MA alone (P<0.05). Compared with model group, the protein expressions of MBP, MPZ, S100, LAMP2 and Beclin1 in sciatic nerve of rats were increased significantly in THD high-dose and low-dose groups, while the protein expressions of PI3K, Akt and mTOR were significantly decreased (P<0.05).CONCLUSIONSTHD may activate Schwann cell autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby improving peripheral nerve injury caused by PTX.
摘要:OBJECTIVETo study the effects of Dianxianqing granules on the tau protein in P301S mice by regulating mitophagy.METHODSTotally 36 P301S mice were randomly divided into model group, Dianxianqing granule group (12.48 g/kg), donepezil hydrochloride group (positive control, 1.3 mg/kg), with 12 mice in each group; another 10 C57BL6 mice were selected as control group. Administration groups were given relevant drug solutions intragastrically, and control group and model group were given constant volume of water intragastrically. The gavage volume was 20 mL/kg, once a day, for consecutive 5 months. During the experiment, the general condition of mice was observed in each group. After the last medication, the learning and memory ability was determined by Y maze test and Morris water maze test; HE staining was used to observe the morphological changes in brain tissue, and Nissl staining was used to observe the structure of neural cells and the number of Nissl bodies in cerebral tissue. Immunohistochemistry was used to detect the expressions of phospho-tau serine 202/threonine 205 (abbreviated as AT8) in brain tissue. Western blot assay was used to determine the expressions of mitophagy-associated proteins [PTEN-induced putative kinase-1 (PINK1), Parkin, microtubule-associated protein 1 light chain 3B (LC3B), p62], synaptic-associated proteins [postsynaptic density protein-95 (PSD-95), synaptophysin (SYP), and growth-associated protein-43 (GAP-43)] and the phosphorylation of tau protein [expressed by the phosphorylation levels of serine 199 (Ser199) and Ser202] in brain tissue.RESULTSThe mice in model group showed symptoms such as white hair, decreased body mass, and lower limb paralysis, with incomplete hippocampal structures in their brain tissue, as well as incomplete cell membrane edges and cell structures; the spontaneous alternating response rate, the times of crossing platform, the number of Nissl bodies, the protein expressions of PINK1, Parkin, LC3B, SYP, GAP-43, and PSD-95 were decreased significantly, compared with control group; swimming latency (fourth and fifth day), the protein expressions of AT8 and p62,the phosphorylation levels of Ser199 and Ser202 were increased or lengthened significantly, compared with control group (P<0.05 or P<0.01). Compared with model group, the above symptoms and indexes of mice were improved significantly in administration groups (P<0.05 or P<0.01).CONCLUSIONSDianxianqing granules can effectively improve cognitive impairment in P301S mice,the mechanism of which may be associated with inducing mitochondrial autophagy, reducing the hyperphosphorylation of tau protein, up-regulating the expression of synaptic-associated proteins in brain tissue,and repairing damaged neural cells.
关键词:Alzheimer’s disease;mitophagy;tau protein;synapse;neural cells;learning and memory disorders
摘要:OBJECTIVETo investigate the effect and mechanism of total flavonoids of Bidens pilosa L. (TFB) on lipopolysaccharide (LPS)-induced neuroinflammation in mice.METHODSFifty C57BL/6 mice were randomly divided into normal control group, LPS group and TFB low-dose, medium-dose and high-dose groups, with 10 mice in each group. TFB low-dose, medium-dose and high-dose groups were given TFB solution intragastrically at 60, 120 and 240 mg/kg, and the normal control group and LPS group were given corresponding volume of normal saline, once a day, for consecutive 21 d. From the 15th day of administration, except for the normal control group, other groups were given LPS (400 μg/kg) intraperitoneally for 7 consecutive days to establish neuroinflammatory model. Brain tissues were taken under anesthesia 4 h after the final administration. The morphological changes of neuronal cells in mice were observed; the contents of nitric oxide (NO), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 were measured, and the expressions of inflammatory pathway-related proteins [inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), myeloid differentiation factor 88 (Myd88) and protein kinase C (PKC)] were measured in the brain tissues of mice.RESULTSCompared with the normal control group, the neuronal arrangement in the hippocampal region of the brain tissue of mice in the LPS group was sparsely disorganized, with a large number of neuronal fixations and shrunken nuclei; the contents of TNF-α, IL-1β, IL-6 and NO in the brain tissue were significantly increased, the contents of IL-10 were significantly decreased, and the relative expressions of iNOS, COX-2, Myd88 and PKC proteins were significantly increased (P<0.05). Compared with the LPS group, the neuronal pathological changes in the brain tissue of mice in the TFB low-dose, medium-dose and high-dose groups were significantly improved, and the changes of the above indices in the brain tissue were significantly reversed (P<0.05).CONCLUSIONSTFB has an inhibitory effect on neuroinflammation, and its mechanism of action may be related to down-regulation of the expressions of inflammatory pathway-related proteins iNOS, COX-2, Myd88 and PKC, and reduction of inflammatory factors release.
摘要:OBJECTIVETo evaluate the cost-effectiveness of serplulimab combined with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma from the perspective of the Chinese healthcare system.METHODSA partitioned survival model with three health states was constructed for cost-effectiveness analysis. Clinical data were extracted from ASTRUM-007. Information on parameters such as cost and health utility was derived from related websites and published literature. The quality-adjusted life years (QALYs) was used as the output index to calculate the incremental cost-effectiveness ratio (ICER), and then compared with three times the per capita gross domestic product (GDP) in China to judge whether it was cost-effective. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model; the cost-effectiveness of applying this plan to subgroup patients with programmed cell death-ligand 1 combined positive score (PD-L1 CPS) ≥10 and the scheme in the context of charitable drug donations was explored.RESULTSAmong advanced or metastatic oesophageal squamous cell carcinoma patients and patients with PD-L1 CPS ≥10, serplulimab combined with chemotherapy could improve health outcomes with an augmentation of cost, compared with placebo combined with chemotherapy,resulting the ICERs were 599 623.64 yuan/QALY and 629 121.57 yuan/QALY, respectively. Therefore, serplulimab combined with chemotherapy was not cost-effective. Sensitivity analysis of single factor showed that the costs of serplulimab were the crucial factor affecting the ICER; probabilistic sensitivity analysis demonstrated basic analysis results were relatively robust. The results of scenario analysis showed that when all patients met the requirements of the charitable drug donation program, serplulimab combined with chemotherapy was cost-effective; the economic outcome of this scheme was reversed compared with the results of the basic analysis.CONCLUSIONSFrom Chinese healthcare perspective, first-line treatment with serplulimab in combination with chemotherapy is not a cost-effective option for patients with advanced esophageal squamous cell carcinoma, but it may be an economic option to implement a charitable drug donation program for all patients or if the price of serplulimab is significantly reduced.
摘要:Abiraterone is commonly used as a targeted drug for the treatment of prostate cancer, which commonly causes adverse drug reactions (ADR), including abnormal liver function, fatigue, nausea and edema, etc. This study reports a 78-year-old man with a history of hepatitis B and liver cirrhosis after prostate cancer resection who was admitted to the First Affiliated Hospital of Henan University of Chinese Medicine. The patient received abiraterone treatment 1 month before admission and developed gastrointestinal symptoms 3 weeks after the treatment and worsened at 4th week with yellowing of the skin, sclera and urine. Unfortunately, the patient died after 5 weeks of abiraterone treatment (1 week after admission). Based on test and examination results, the patient was diagnosed with acute-on-chronic liver failure (ACLF). This paper analyzes the patient’s medical history and the relevant treatment in detail. It is evaluated that ACLF and abiraterone are “probably” related based on Naranjo ADR Probability Scale, suggesting abiraterone may induce severe ADR of liver failure in patients with chronic liver diseases such as cirrhosis. These patients should be monitored dynamically for changes in liver function and treated prophylactically with liver-protective drugs if necessary.
关键词:acute-on-chronic liver failure;adverse drug reaction;liver failure
摘要:OBJECTIVETo analyze influential factors for dabigatran exposure in elderly patients with non-valvular atrial fibrillation.METHODSThe clinical information of 75 elderly patients diagnosed with non-valvular atrial fibrillation was collected from our hospital in Jan. 2019-Jun. 2020. One or two steady-state blood drug concentration samples were collected from each patient. NONMEM 7.2.0 software was used to establish a population pharmacokinetics model of dabigatran; the effects of different covariates on the apparent clearance of dabigatran were investigated, and the final model was verified by goodness of fit and Bootstrap method; NONMEM 7.2.0 software was used to analyze the drug exposure of ordinary elderly patients and elderly patients after taking dabigatran ester in different disease states.RESULTSTotally 122 blood concentration samples of dabigatran were collected. Advanced age, creatinine clearance and history of chronic heart failure were screened out as three significant covariates that influenced the clearance of dabigatran in elderly patients. The exposure of population with advanced age increased by about 50% compared with the general elderly, the exposure of population with history of chronic heart failure increased by nearly 30% compared with population without, and the exposure of population with moderate and severe renal injury increased by about 30% and 80% compared with mild.CONCLUSIONSAdvanced age, renal injury and history of chronic heart failure are influential factors for elevated systemic exposure of dabigatran.
摘要:OBJECTIVETo analyze the clinical characteristics of nephrotic syndrome induced by sunitinib, and to provide reference for clinical rational drug use.METHODSRetrieved from CNKI, VIP, Wanfang data, PubMed, Web of Science and Medline, case report about sunitinib-induced nephrotic syndrome were collected from the inception to Oct. 30th, 2022. Those case reports were analyzed statistically in terms of gender, age, primary disease, drug use, clinical manifestations, treatment and outcome.RESULTSA total of 15 pieces of literature were collected and 17 patients were involved, including 10 males and 7 females. The average age of patients was (59.35±15.72) years. Among 17 patients, there were 10 patients with renal cell carcinoma and 7 patients with gastrointestinal stromal tumor, all of whom received evidence-based medication; the dosage of sunitinib in 15 cases was recorded, and all of them were within the recommended range of the instructions; 9 patients received combined therapy; the time from sunitinib application to the occurrence of nephrotic syndrome was 21 days-52 months, of which 11 cases were ≤2 years. The clinical manifestations in 13 patients were described, including edema, oliguria, foamy urine, weight gain, fatigue, dyspnea on exertion, etc. Eight patients had other adverse reactions induced by sunitinib before suffering from nephrotic syndrome, including new hypertension or worsening of original hypertension, and hand-foot syndrome. Renal biopsy mainly manifested as thrombotic microangiopathy, focal segmental glomerular sclerosis and immune complex glomerulonephritis. Sunitinib withdrawal or dosage reduction was adopted in all patients, and they were given symptomatic treatment such as glucocorticoids and antihypertensive agents. Symptoms of 16 patients were improved, and renal function of one patient deteriorated and hemodialysis was started. Sunitinib was re-challenged in 6 patients, elevated creatinine and substantial proteinuria recurred in 5 patients.CONCLUSIONSIn clinical use of sunitinib, it is advisable to periodically monitor renal function. In case of deterioration of renal function, albuminuria, edema, etc., relevant examinations should be implemented in time, and symptomatic intervention should be taken as soon as possible. Besides, we should be alert to the recurrence of nephrotic syndrome after sunitinib rechallenge.
关键词:adverse drug reaction;nephrotic syndrome;literature analysis
摘要:OBJECTIVETo analyze the clinical manifestation and characteristics of ocular adverse drug reaction (ADR) related to dupilumab, so as to provide reference for clinically safe drug use.METHODSRetrieved from CNKI, Wanfang data, VIP and PubMed databases, the case reports about ocular ADR caused by dupilumab were collected, and then analyzed statistically in terms of gender, age, primary disease, drug use, occurrence time of ADR, main clinical manifestations, treatment or outcome, etc.RESULTSA total of 20 pieces of literature were selected, involving 46 patients, among which there were 29 males and 17 females. Mainly patients were under 60 years old. The results of the association evaluation was given as follows: 13 were “very likely” and 33 were “likely”. All patients were treated with dupilumab for atopic dermatitis (AD) without off-label medication. The occurrence time of ADR was 2 weeks to 2 years after administration, mainly within 6 months after medication. All patients received dupilumab monotherapy except that 3 patients with hypertension and 1 patient with chronic obstructive pulmonary disease and human immunodeficiency virus received other drugs simultaneously. Twenty-eight patients had a history of allergic disease, and 11 patients had a history of eye disease. Ocular ADRs were mainly conjunctivitis and uveitis, and the clinical manifestations mainly included conjunctival congestion, swelling, eye secretions, etc. Ten patients developed severe ADR, including uveitis, severe conjunctivitis, and tear point stenosis; 45 patients were improved after symptomatic treatment. AD, serious initial symptoms of AD, allergic disease and underlying ocular diseases might be the high-risk factors of ocular ADR caused by dupilumab.CONCLUSIONSWhether the patient has the history of allergic diseases and basic eye diseases should be asked in detail before clinical use of dupilumab. When using the drug, attention should be paid to monitoring whether the patient has intraocular inflammation, be alert to the occurrence of new or serious ADR, and give timely symptomatic treatment to ensure the safety of drug use.
关键词:retinitis;uveitis;ocular adverse drug reaction;literature analysis
摘要:OBJECTIVETo evaluate the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram, and to provide evidence-based reference for precision medication.METHODSRetrieved from PubMed, Embase, the Cochrane Library, CNKI, Wanfang data and SinoMed, clinical studies about the association of gene polymorphism with efficacy and safety of citalopram/escitalopram were collected. Meta-analysis was performed with RevMan 5.3 software after literature screening, data extraction and quality evaluation based on Newcastle-Ottawa scale.RESULTSTotally 35 pieces of literature were included, all of which were cohort studies, with a total of 9 836 patients. Meta-analysis showed that the SLC6A4 gene 5-serotonin transporter linked polymorphic region (HTTLPR) LL genotype was associated with high response rate of citalopram/escitalopram [LS/SS vs. LL: OR=0.47, 95%CI (0.22, 0.98), P=0.05]; results of subgroup analysis suggested a higher correlation in white people with LL genotype and escitalopram; there was no significant correlation of HTTLPR genotype with remission rate [LS/SS vs. LL: OR=0.92,95%CI(0.77, 1.10), P>0.05; SS vs. LL/LS:OR=0.73, 95%CI(0.45, 1.19), P>0.05] or overall incidence of ADR in patients with gene SLC6A4; but high expression of rs25531 LA was significantly associated with reduced incidence of ADR(P<0.05). CYP2C19*2/*3 allele was significantly associated with slowed metabolism, higher response rate and increased incidence of ADR.CONCLUSIONSHTTLPR LL genotype is associated with the increased response rate of citalopram/escitalopram, but no significant correlation with safety is found, while CYP2C19*2/*3 allele is significantly associated with higher response rate and reduced tolerability.
摘要:OBJECTIVETo systematically review the efficacy and safety of tranexamic acid (TXA) for hemostasis in cancer patients before and during surgery, and to provide evidence-based reference for clinical drug use.METHODSRetrieved from PubMed, Embase, the Cochrane Library, CNKI, VIP and Wanfang databases, randomized controlled trials (RCTs) about tranexamic acid (trial group) versus 0.9% Sodium chloride injection, Lactated Ringer’s solution, Compound electrolyte solution or placebo (control group) for cancer surgery were electronically searched from the inception to June 9, 2022. After literature screening and data extraction, the quality of included RCTs were evaluated by bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0. RevMan 5.3 software was used for meta-analysis or descriptive analysis, sensitivity analysis and publication bias analysis.RESULTSA total of 2 032 patients in 22 RCTs were included for meta-analysis. Results of meta-analysis showed that the blood transfusion rate [RR=0.59, 95%CI (0.50, 0.69), P<0.000 01] and the volume of erythrocyte suspension infusion [MD=-0.53, 95%CI (-0.92, -0.14), P=0.007] in trial group were significantly lower than control group; there was no statistical significance in the incidence of thromboembolic events [RR=0.44, 95%CI (0.16, 1.17), P=0.10] or post-operative mortality [RR=1.27, 95%CI(0.32,5.08), P=0.73] between two groups. Results of descriptive analysis showed that the total blood loss and postoperative drainage volume were still controversial between two groups. The results of sensitivity analysis showed that the results were basically stable. The results of publication bias analysis showed that there was little possibility of publication bias in this study.CONCLUSIONSTXA can significantly decrease the blood transfusion, reduce the volume of erythrocyte suspension infusion, whereas does not increase the incidence of thromboembolic events and post-operative mortality in cancer surgery.
摘要:OBJECTIVETo systematically analyze the related clinical research of therapeutic drugs for rotavirus infection in children, and to provide reference for the improvement of scientific and normative implementation in clinical trials.METHODSPubMed, the Cochrane Library and Embase databases were systematically searched, and English literature on randomized controlled trials (RCTs) about therapeutic drugs for pediatric rotavirus infection published between 2000 and 2022 was included. After literature screening and data extraction, the quality of the included literature was evaluated using the bias risk assessment scale recommended by Cochrane Handbook for Systematic Reviews. The research objectives, overall design, subject inclusion and exclusion criteria, interventions, course of treatment, follow-up visits, efficacy and safety evaluations, and results were analyzed descriptively. RESULTS &CONCLUSIONSA total of 17 RCTs were included, involving 1 345 subjects. The purpose included relieving rotavirus infection-induced diarrhea, promoting rotaviral shedding, improving clinical symptoms such as dehydration, fever, vomiting, and shortening hospital stays, etc. All trials were randomized and single-center studies, mostly double-blind (13 trials) and placebo-controlled (16 trials), and 64.71% had sample size estimation. The inclusion and exclusion criteria included diarrhea attack, virus detection, clinical symptoms, disease types and drugs, etc. The interventions included probiotics (8 trials), biological agents (3 trials), anti-infective agents (3 trials), etc. Most of treatment course was 1-5 days (13 trials). A total of 58.82% were designed for follow-up. In the validity evaluation, diarrhea attack, microbiology test and fecal culture, clinical symptoms such as dehydration, fever and vomiting, length of hospital stays or duration of symptoms were included. Vesikari scale, WHO criteria and researcher evaluation were the evaluation criteria. In the safety evaluation, 10 trials were designed for adverse events/adverse reaction observation; only one trial listed ethical approval numbers. The information of literature included in the study covers the basic elements for the design of RCTs of drugs for rotavirus infection in children. Nevertheless, all are single-center studies. Partial studies lack the basis for sample size estimation and related contents of drug combination, and the quality needs to be improved. In the future, the high-quality multi-center clinical trials should be further conducted, with objective measurement indexes as the validity results, and the ethical review and safety evaluation should be emphasized.
关键词:children;randomized controlled trials;design elements
摘要:OBJECTIVETo comprehensively evaluate four weekly preparations of glucagon-like peptide-1 receptor agonist(GLP-1RA) marketed in China,and to provide evidence for hospitals to optimize drug catalogs and clinical rational drug use.METHODSMini health technology assessment method was used to establish detailed evaluation rules according to A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions, and conduct comprehensive evaluation of four GLP-1RA weekly preparations from aspects of pharmaceutical characteristics, effectiveness, safety, economy and other attributes.RESULTSMini health technology assessment scores of the four GLP-1RA weekly preparations from high to low were dulaglutide 78.60 points, semaglutide 77.35 points,polyethylene glycol loxenatide 67.40 points, and exenatide microspheres 65.50 points, respectively. Dulaglutide had advantages in reducing blood sugar, arteriosclerotic cardiovascular disease, kidney benefits, and cost-effectiveness. Semaglutide had advantages in reducing blood sugar and weight loss, but its cost-effectiveness was lower than that of dulaglutide. Exenatide microspheres had advantages in the use of children, but its daily average treatment cost is the highest. Polyethylene glycol loxenatide needed further clinical evidence.CONCLUSIONSFour GLP-1RA weekly preparations all have high pharmaceutical comprehensive scores. Dulaglutide and semaglutide may have more comprehensive pharmaceutical value among them, while the use of exenatide microspheres for children is unique.
关键词:Mini health technology assessment;semaglutide;dulaglutide;exenatide microspheres;polyethylene glycol loxenatide
摘要:OBJECTIVETo analyze the research status and hotspots of wine processing of Chinese medicine, and to provide reference for its related research.METHODSRelated literature about wine processing research in Chinese medicine was retrieved from CNKI and Web of Science (WOS). VOSviewer 1.6.18 and CiteSpace 6.1.1R2 software were used to visualize the core authors, research institutions, keywords, and other contents.RESULTSA total of 962 Chinese literature and 57 English literature were included in the study. In total, the trend in the amount of Chinese and English literature was on the rise during 2000-2022. The analysis of the authors showed that ZHANG Xuelan and CAI Baochang had the most publications in Chinese and English literature. Research institutions were mainly Chinese medicine universities, and Chengdu University of Chinese Medicine and Nanjing University of Chinese Medicine were the research institutions with the largest number of Chinese and English literature published. The analysis of keywords in Chinese and English literature showed that the wine-processing research of Chinese medicine mainly focused on wine-processed varieties, chemical constituents, wine-processed process, and quality standards. Response surface method, chroma value, metabolomics, and action mechanism had become current research hotspots.CONCLUSIONSThe related research of wine processing for Chinese medicine is still in the development period. In the future, the response surface method to optimize the wine-processed process and the combination of metabolomics with related technologies of other omics to reveal the pharmacodynamic mechanism of wine processing for Chinese medicine is still the future development trend. In the future, cooperation between institutions should be further strengthened, and research on the use of excipients and alcohol should be strengthened. Modern analytical methods should be utilized to enhance the efficiency of wine processing for Chinese medicine, thereby promoting the modernization and internationalization of wine processing for Chinese medicine.
关键词:stir-frying with wine;wine steam-processed;bibliometrics;VOSviewer;CiteSpace;visualization analysis
摘要:As an adjuvant alternative therapy, phototherapy is widely used for early diagnosis and late treatment of breast cancer due to its non-invasive treatment characteristics. But the application of phototherapeutic agents has been limited in the clinic due to poor hydrophobicity and tissue targeting, low photostability, and obvious toxic side effects in vivo. With the development of nanotechnology, new composite nano-phototherapy agents have emerged. This paper summarizes the latest developments and findings of new composite nano-phototherapy agents for phototherapy in the field of breast cancer treatment in the past 5 years. With the development of multifunctional nanomaterials in the field of breast cancer imaging diagnosis and treatment, the modified phototherapy agent achieved further development respectively from improving light response to improve the light thermal conversion or increasing the generation of reactive oxygen species, targeting tumor microenvironment, immune cells and cancer cell surface receptors to achieve drug controllable response release, using biomimetic materials and endogenous substances to improve biocompatibility. Although phototherapeutic agents exhibit high cell-killing rates in the treatment of metastatic breast cancer models and effectively inhibit their recurrence and metastasis, problems remain regarding the safety and compatibility of synergistic therapy. Future studies can not only improve the existing effects of phototherapeutic agents, but also develop oral drugs with more convenient routes based on immunotherapy to amplify the immune response and resist breast cancer through multiple routes.
关键词:nanomaterials;photothermal therapy;photodynamic therapy;breast cancer
摘要:Lung cancer is mainly non-small cell lung cancer (NSCLC). NSCLC is often associated with epidermal growth factor receptor (EGFR) gene mutations. Currently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are the preferred first-line treatment option for EGFR-mutated NSCLC. Furmonertinib is the second third-generation EGFR-TKI marketed in China, which is developed independently by China. In this review, it is found that furmonertinib has dual activity, strong tumor suppression, high selectivity, and high safety profile, and is effective in the treatment of EGFR-sensitive mutation, EGFR exon 20 T790M resistance mutation, EGFR exon 20 insertion mutation, and central nervous system metastasis NSCLC, and its relevant clinical trials are only enrolled in Chinese patients, which is more guidance for Chinese NSCLC patients in China.