Latest ArticlesStandardizing the management of drugs used in clinical trials is one of the important means to protect the safety of trial participants and ensure that the trial results are scientifically reliable. The management of trial drugs runs throughout the entire clinical trial process, with some hospitals centralizing the management and others managing it within departments. Participants in the process include doctors, nurses, and pharmacists, among others. Investigate the management of investigational drugs in 15 hospitals and combine domestic relevant regulations and guidelines to standardize the management process of investigational drugs. A central pharmacy staffed by dedicated pharmacy personnel should be preferred, and if a departmental management model is used, a research physician/nurse or a pharmacy personnel with the necessary qualifications and competencies should be appointed as the drug manager. The reception and inventory of clinical trial drugs, as well as the return of drugs to the sponsor, should be completed by the institutional drug manager. The distribution of clinical trial drugs can be authorized to individuals with a professional background in pharmacy who have obtained professional qualification certificates or licensed pharmacist certificates. If non-pharmacist personnel distribute clinical trial drugs, other equivalent documents should be used instead of dispensing drugs based on prescriptions.
Sacubitril valsartan sodium tablets are a novel supramolecular co-crystal drug that combines the dual effects of angiotensin receptor blockade and neprilysin inhibitor. It has shown broad application prospects in heart failure, hypertension, maintaining water sodium balance in the body, and protecting target organs, etc. It is a major breakthrough in cardiovascular treatment drugs in recent years. It is clinically used in China for chronic heart failure in adult patients with reduced ejection fraction and primary hypertension. In recent years, pharmaceutical co-crystals has become a hot topic in the research of crystalline drugs, and sacubitril valsartan sodium tablets, as a marketed co-crystal drug, have attracted industry attention. This article summarizes the characteristics of sacubitril valsartan sodium co-crystal drug, the application and approval cases through relevant literature investigation, and discussses pharmaceutical research of the formulation, in order to provide some references for the research and development of generic drugs.
Virus are one of the main pathogens that cause many serious diseases in humans, animals and plants. Antivirals are a class of drugs specifically used to treat viral infections. Although different virus replicate in different ways, infecting the human body has several stages in common, including entry, biosynthesis, assembly, and release. Virus of the same genus are highly similar in protein structure and sequence, so they can be used as common targets for antiviral drug development. This article reviews the processes of viral infection in humans and the targeted antiviral drugs designed for these processes, including inhibitors targeting the surface subunit (SfS) and transmembrane subunit (TmS) of viral enveloped glycoprotein, viral entry inhibitors targeting host proteins, RNA-dependent RNA polymerase and RNA/DNA-dependent DNA polymerase inhibitors and virus protease inhibitors, in order to provide clues for the development of antiviral drugs for future epidemics.
To explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency, which was based on G protein-coupled receptor 41 (GPR41)/GPR43-mediated mitogen-activated protein kinase (MAPK) signaling pathway.
The three-factor composite modeling method of eating disorder, diarrhea and fatigue was used to establish a model of spleen qi deficiency, and the rats were randomly divided into model, honey-processed Hedysari Radix, probiotics and blank groups with 15 rats per group. The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix. The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage. The blank and model groups were given the same dose of distilled water by gavage. Four groups were treated for 15 d with once a day. The expression levels of GPR41, GPR43, P38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular regulatory protein kinase 1/2 (ERK1/2) in colon tissues were detected by Western blotting.
The relative expression levels of GPR41 in the blank, model, honey-processed Hedysari Radix and probiotics groups were 0.95±0.07, 0.45±0.03, 0.84±0.19 and 0.86±0.20; the relative expression levels of GPR43 were 1.17±0.11, 0.41±0.06, 0.66±0.03 and 0.57±0.01; the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01, 0.43±0.01, 0.39±0.01 and 0.36±0.02; the phosphorylated JNK/JNK ratios were 0.58±0.05, 1.47±0.10, 0.90±0.11 and 0.90±0.11; the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33, 3.19±0.03, 2.01±0.17 and 2.23±0.59, respectively. Compared with the model group, the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups (P<0.05, P<0.01).
The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.
Rheumatoid arthritis (RA) is an inflammatory disease mainly associated with polyarthritis. It is mainly due to the joint swelling and joint inflammation caused by immune cells. The alkaloids in traditional Chinese medicine can reduce the level of pro-inflammatory factors and increase the level of anti-inflammatory factors, reduce the joint synovial tissue hyperplasia, inflammatory cell infiltration and new blood vessel formation, inhibit the differentiation of osteoclasts, and then play an anti-RA role. Therefore, the review used the effects and mechanisms of alkaloids for RA to inform the development of new drugs for RA.
To observe the clinical efficacy and safety of hydrocortisone injection combined with continuous blood purification in the treatment of sepsis patients.
Sepsis patients were randomly divided into control group and treatment group. The control group received continuous blood purification treatment; on the basis treatment of control group, the treatment group received hydrocortisone 200 mg, qd, intravenous infusion. Two groups were treated for 1 week. The clinical efficacy, levels of inflammatory cytokines, cellular immune function indicators, and safety were compared between two groups.
Fifty-six cases were enrolled in the treatment group, 5 cases were excluded, and ultimately 51 cases were included in the statistical analysis. Fifty-five cases were enrolled in the control group, 4 cases were excluded, and ultimately 51 cases were included in the statistical analysis. After treatment, the total effective rates of the treatment and control groups were 94.12% (48 cases/51 cases) and 74.51% (38 cases/51 cases) with statistical significant difference (P<0.05). After treatment, the levels of C-reactive protein in the treatment and control groups were (12.21±2.35) and (15.18±2.25) mg·L-1, the levels of procalcitonin were (0.49±0.13) and (0.78±0.21) ng·mL-1, the levels of CD3+ were (58.72±5.13)% and (54.21±4.47)%, the CD4+/CD8+ ratios were 1.71±0.23 and 1.43±0.17, respectively. The differences were statistically significant (all P<0.05). The adverse drug reactions of treatment group were chest tightness, nausea, and vomiting, while those in the control group were hypotension, nausea, and vomiting. The total incidences of adverse drug reactions in the treatment and control groups were 9.80% and 5.88%, without significant difference (P>0.05).
Hydrocortisone injection combined with continuous blood purification have a definitive clinical efficacy in the sepsis patients, which can improve the patients’ immune function, reduce inflammatory reactions, without increasing the incidences of adverse drug reactions.
To explore the mechanism of action of tanthine in the treatment of allergic rhinitis (AR) complicated with asthma in rats by regulating microRNA-27a-3p (miR-27a-3p) targeting thymic stromal lymphopoietin (TSLP).
The AR-asthma rat model was established using ovalbumin (OVA) sensitization and nasal drip attack method. Fifty rats were divided into control group (equal volume 0.9% NaCl), model group (AR-asthma model+equal volume 0.9% NaCl), experimental group (AR-asthma model+100 mg·kg-1 xanthortin) and miR-27a-3p inhibitor group (caudal vein injection of 0.5 nmol·μL-1 miR-27a-3p inhibitor 10 μL on the basis of the experimental group), si-TSLP group (0.5 nmol·μL-1 si-TSLP 10 μL intravenously injected on the basis of miR-27a-3p inhibitor group), 10 rats in each group. Serum immunoglobulin E (IgE), interleukin-2 (IL-2), IL-13 and tumor necrosis factor-α (TNF-α) levels of rats were detected by enzyme-linked immunosorbent assay. The level of superoxide dismutase (SOD) was detected by xanthoxine oxidase method. The level of malonaldehyde (MDA) was detected by thiobarbituric acid method (TBA).
The levels of IgE in control group, model group, experimental group, miR-27a-3p inhibitor group and si-TSLP group were (18.33±3.53), (89.95±17.62), (55.70±10.08), (78.43±15.30) and (47.87±9.44) ng·mL-1, respectively; IL-2 levels were (8.01±1.36), (19.61±3.94), (14.12±2.51), (17.33±3.18) and (11.89±2.03) pg·mL-1, respectively; IL-13 levels were (6.79±1.33), (34.15±7.02), (24.70±5.13), (35.97±7.24) and (20.53±4.26) pg·mL-1, respectively; TNF-α levels were (94.08±19.07), (312.47±58.61), (209.78±41.49), (296.42±55.99) and (187.45±37.28) pg·mL-1, respectively; SOD levels were (29.14±5.04), (13.25±2.63), (24.19±4.89), (17.28±3.16) and (33.94±5.87) U·mg prot-1, respectively; MDA levels were (2.26±0.51), (4.43±0.72), (3.17±0.58), (3.94±0.69) and (2.62±0.45) nmol·m gprot-1, respectively. The above indicators were compared between control group and model group, model group and experimental group, experimental group and miR-27a-3p inhibitor group, miR-27a-3p inhibitor group and si-TSLP group. The differences were statistically significant (all P<0.05).
Xanthine can improve oxidative stress and reduce inflammation of AR complicated with asthma in rats, and its mechanism may be related to the regulation of miR-27a-3p targeting TSLP.
To investigate the expression of microRNA-508-3p (miR-508-3p) in epithelial ovarian cancer (EOC) tissue, its impact on the migration and invasion of ovarian cancer cells, and its regulatory relationship with zinc-finger E-box-binding homeobox 1 (ZEB1).
The surgical resection of EOC cancer tissues and paired adjacent normal tissues were collected. SKOV3 cells were divided into the NC mimic group (transfected with NC mimic), miR-508-3p mimic group (transfected with miR-508-3p mimic), si-NC group (transfected with si-NC), si-ZEB1 group (transfected with si-ZEB1) and co-transfection group (co-transfected with si-ZEB1 and miR-508-3p mimic). The mRNA expression levels of miR-508-3p and ZEB1 in EOC cancer tissues, adjacent normal tissues and five groups of cells were measured by real-time quantitative polymerase chain reaction. The Transwell assay was used to detect the cell migration and invasion abilities.
The relative expression levels of miR-508-3p in EOC tissues and adjacent normal tissues were 0.77±0.36 and 1.07±0.40, the relative expression levels of ZEB1 mRNA in EOC tissues and adjacent normal tissues were 2.10±1.21 and 1.29±0.95, and the differences were statistically significant (all P<0.01). The migration cell number of the NC mimic, miR-508-3p mimic, si-NC, si-ZEB1 and co-transfection groups was 633.00±32.49, 319.20±19.89, 650.40±25.85, 375.00±17.25 and 129.40±17.10; the invasion cell number was 527.20±25.01, 288.60±16.68, 520.00±25.83, 293.40±18.37 and 76.60±8.76; the relative expression levels of miR-508-3p were 1.05±0.37, 3.94±1.21, 1.01±0.21, 1.26±0.34 and 3.40±0.41; the relative expression levels of ZEB1 mRNA were 1.00±0.04, 0.58±0.05, 1.00±0.08, 0.54±0.07 and 0.29±0.03, respectively. The above indicators showed statistically significant differences between the miR-508-3p mimic group and the NC mimic group, between the si-NC group and the co-transfection group (P<0.01, P<0.05).
MiR-508-3p is lowly expressed in EOC cancer tissue, and it may inhibit the migration and invasion of ovarian cancer cells by targeting ZEB1 expression.
To observe the long-term survival benefit status of bevacizumab injection combined with chemotherapy in the treatment of advanced ovarian cancer.
The patients with advanced ovarian cancer were classified into control group and treatment group according to cohort method. The control group was treated with 175 mg·m-2 of paclitaxel injection + area under curve (AUC) 5 intravenous infusion of carboplatin injection once every 3 weeks for 6 cycles, and on the basis of the control group, the treatment group was additionally given intravenous injection of 15 mg·kg-1 of bevacizumab injection in the second cycle, once every 3 weeks, maintained monotherapy after 6 cycles until disease progression (up to 22 cycles of treatment). The solid tumor efficacy at 6 cycles of treatment and levels of serum tumor markers [carbohydrate antigen (CA) 125, CA199, human epididymis protein 4 (HE4)], vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), long term survival status (overall survival time, progression-free survival time) and safety evaluation before treatment and at 6 cycles of treatment were compared.
There were 51 cases in the control group and 31 cases in the treatment group. After 6 cycles of treatment, the total effective rates of the treatment group and the control group was 77.42% (24 cases/31 cases) and 52.94% (27 cases/51 cases), respectively, and the difference was statistically significant (P<0.05). After 6 cycles of treatment, serum CA125 levels in treatment group and control group were (63.71±8.53) and (73.09±9.55) U·mL-1; the CA199 levels were (58.97±10.87) and (69.39±12.45) U·mL-1; the HE4 levels were (117.96±22.73) and (155.60±30.92) pmol·L-1; levels of VEGF were (285.50±60.42) and (377.82±73.31) ng·L-1; the levels of MIF were (20.26±3.42) and (22.34±3.19) μg·L-1, the progression-free survival time was 7 (0, 17) and 2 (0, 6) months; there were statistically significant differences in the above indexes between the treatment group and the control group(P<0.05, P<0.01, P<0.001). The overall survival time in treatment group and control group was 10 (6, 20) months and 8 (4, 11) months. The differences were statistically significant(P>0.05). The adverse drug reactions in treatment group were mainly nausea and vomiting, hypertension and bone marrow suppression while the adverse drug reactions in control group were mainly nausea and vomiting and bone marrow suppression, and the total incidences of adverse drug reactions were 45.16% (14 cases/31 cases) and 35.29% (18 cases/51 cases) respectively (P>0.05).
Bevacizumab injection combined with chemotherapy has good clinical efficacy in the treatment of advanced ovarian cancer, and significantly prolong the progression-free survival time of patients.
The development of breast cancer is closely related to the information transfer in its microenvironment. As a novel information communication tool, exosomes present non-coding RNAs that are involved in breast cancer cell proliferation, migration, invasion, tumour-associated fibroblasts ogenesis, cell cycle, degradation of oncogenes, etc. This paper reviews the relationship between exosomes and the tumour microenvironment and the role of their presenting non-coding RNAs on breast cancer as well as their clinical applications in order to provide new ideas for biological research and therapeutic strategies.