Latest ArticlesAlthough some progress had been made in the treatment of chronic hepatitis B virus(HBV)infection,current first-line drugs failed to completely eliminate the covalently closed circular DNA(cccDNA)of HBV so as to completely eliminate HBV. Targeted therapy can specifically bind to the target sites, thereby blocking virus invasion, virus transcription, and protein translation, achieving precise treatment. Therefore, this article summarized and reviewed the targets at different stages of the HBV life cycle from the perspectives of targeting virus entry, targeting cccDNA, targeting core protein, targeting hepatitis B surface antigen(HBsAg)release, and targeting viral transcription, with a view to providing ideas for drug development against HBV infection.
To investigate the effects of Platycodon grandiflorum extract(PGE)on the proliferation and metastasis of fibroblast-like synovial cells in rheumatoid arthritis(RA)and its mechanism of action.
Fibroblast-like synovial cells MH7A were divided into control group, PGE-L group(25 mg·L-1 PGE), PGE-M group(50 mg·L-1 PGE), PGE-H group(100 mg·L-1 PGE), PGE + angiotensin(Ang)Ⅱ group(100 mg·L-1 PGE + 100 nmol·L-1 Ras homologous gene family member A(RhoA)/Rho kinase(ROCK)pathway activator AngⅡ), and treated accordingly. Cell proliferation, apoptosis, migration and invasion were detected by CCK-8 method, flow cytometry and Transwell, respectively.The expression levels of related proteins were detected by Western blot, and the RhoA activity in cells was detected by GST-pull down method.
Compared with the control group, absorbance value(24, 48 and 72 h after PGE treatment),the number of migrating and invading cells, the expression of cyclin D1, matrix metalloproteinase(MMP)-2, MMP-9,ROCK1 and ROCK2 proteins, and the activity of RhoA were significantly reduced, and p21 protein expression and the apoptosis rate were increased in PGE-L group, PGE-M group, and PGE-H group, and the higher the concentration of PGE,the more obvious the corresponding trend was(P<0.05). Compared with the PGE-H group, the absorbance value(24, 48,72 h after PGE treatment), the number of migratory and invasive cells, the expression of cyclin D1, MMP-2, MMP-9, ROCK1,ROCK2 protein and RhoA activity were increased, amd p21 protein expression and apoptosis rate decreased in PGE + Ang Ⅱgroup(P<0.05).
PGE can inhibit the proliferation and metastasis of MH7A cells, which may be related to the inhibition of RhoA/ROCK pathway.
To study the effect of butylphthalide on oxidative stress indicators and its signaling pathway related factors in patients with acute cerebral infarction.
A total of 100 patients with acute cerebral infarction admitted to the hospital from August 2020 to April 2021 were divided into control group and study group by stratified blocked randomization method, with 50 patients in each group. The control group underwent conventional treatment, and the study group was treated with butylphthalide injection (100 mL, iv gtt, bid) for 14 d on the basis of conventional treatment. The two groups were compared in terms of neurological impairment score, oxidative stress indicators, related signaling pathway factors, nerve injury markers, C-reactive protein (CRP) and low-density lipoprotein (LDL) levels, as well as clinical efficacy and safety before and after treatment.
There were 3 cases in the control group and 2 cases in the study group dropped out during treatment. Finally, 47 cases in the control group and 48 cases in the study group were included respectively. After treatment, the level of malondialdehyde in the study group was significantly lower than that in the control group, while superoxide dismutase and glutathione peroxidase were significantly higher than those in the control group (P<0.05); the Kelch-like ECH-associated protein 1 (Keap1) mRNA in the study group was significantly higher than that in the control group, while nuclear factor E2 related factor (Nrf2) and antioxidant response element (ARE)mRNA were significantly lower than those in the control group (P<0.05). The levels of CRP and LDL in the study group were significantly lower than those in the control group (P<0.05). The National Institutes of Health Stroke Scale score and the levels of myelin basic protein, neuron-specific enolase, and S100 calcium binding protein B in the study group were significantly lower than those in the control group (P<0.05). The total effective rate of treatment in the study group was significantly higher than that in the control group (96% vs. 81%, P<0.05), with no statistically significant difference in the total incidence of adverse reactions between the two groups (6% vs. 8%, P>0.05).
Butylphthalide is effective in the treatment of patients with acute cerebral infarction, which may inhibit oxidative stress and relieve neurological damage through affecting the Keap1-Nrf2/ARE signaling pathway, and also has the advantage of regulating lipid metabolism abnormalities and reducing inflammation in the body.
To evaluate the economics of pembrolizumab in the first-line treatment of patients with unresectable or metastatic microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer.
Based on the Chinese healthcare system, a partitioned survival model was constructed to compare the cost and utility between pembrolizumab and standard of care using KEYNOTE-177 clinical trial data. The cycle length and time horizon of the model was set as 21 days and 10 years, respectively. The incremental cost-effectiveness ratio (ICER) was used as the evaluation indicator. Scenario analysis and sensitivity analysis were also performed.
Compared with standard of care, the ICER of pembrolizumab was 221 546.85 yuan·QALY-1, which was lower than 3 times China’s per capita gross domestic product (GDP) in 2021. The pembrolizumab was dominant when patient assistance program was considered. The results of one-way sensitivity analysis showed that the proportion of pembrolizumab on subsequent treatment in the standard of care, pembrolizumab price and discounting exhibited the significant impact on the ICER. The results of probability sensitivity analysis showed that under the 3 times China’s per capita GDP in 2021, the probability of pembrolizumab being cost-effectiveness was 63.36%.
Pembrolizumab has a cost-effective advantage over standard of care as first-line treatment for unresectable or metastatic MSI-H/dMMR colorectal cancer in China.
To study the effect of a single dose of dexamethasone on reversal of rocuronium deep neuromuscular blockade (NMB) by sugammadex.
A total of 80 patients undergoing laparoscopic colon surgeries under general anesthesia were selected, with ASA Ⅰ- Ⅱ, and not taking steroid drug medication. The patients were randomly divided into 2 groups with 40 cases in each group. Before anesthesia induction, the trial group was given dexamethasone 0.15 mg·kg-1, and the control group was given the same amount of chloride sodium injection. The induction and maintenance programs of anesthesia were the same in both groups. Rocuronium was administered intravenously for 5 - 10 µg·kg-1·min-1 to maintain deep muscle relaxation, and the post-tetanic count (PTC) was maintained at 0 - 2. After operation, all patients were immediately intravenously injected with sugammadex at a dose of 2 mg·kg-1 when PTC was 1 - 2. The time for train of four-ratios (TOFR) to reach 0.9, extubation time and occurrence of adverse reactions were recorded.
The time of TOFR recovery to 0.9, extubation time and post-anesthesia care unit (PACU) residence time were (6.0±0.7),(7.5±0.5) and (36.8±5.8) min in the control group, and (6.0±0.6), (7.7±0.5) and (39.7±6.2) min in the trial group, respectively,with no significant differences between the two groups (P>0.05). There were no differences in mean arterial pressure and heart rate between the two groups before surgery, at the time of sugammadex administration, and 5 and 10 min after administration (P>0.05). No adverse reactions occurred in the both groups.
Dexamethasone 0.15 mg·kg-1 has no significant effect on the reversal of deep NMB by sugammadex.
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors comprise a new class of oral hypoglycemic agents that promote the excretion of urine sugar and reduce blood sugar mainly by inhibiting the reabsorption of glucose in proximal renal tubules. Numerous clinical studies have found that SGLT-2 inhibitors have good effects on cardiovascular system. At the same time, many basic studies have found that a variety of SGLT-2 inhibitors exhibit anti-inflammatory activity in both cellular and animal models, and the cardiovascular protective mechanism may be closely related to inhibiting inflammatory response. For example, canagliflozin inhibits inflammatory response by enhancing anti-inflammatory signaling pathways such as AMP activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Dapagliflozin significantly reduces the expression of inflammatory factors such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and promotes the polarization of macrophages towards anti-inflammatory phenotype. Empagliflozin reduces cardiac inflammation in diabetes cardiomyopathy, hypertension, and heart failure models.
Antibody-drug conjugate (ADC), a new type of targeted drugs for breast cancer, is formed by connecting a chemotherapeutic drug with a monoclonal antibody using a linker. The monoclonal antibody is used as a carrier to transport the chemotherapeutic drug to the specific tumor cells, thereby exerting anti-tumor effects. ADCs are classified into human epidermal growth factor receptor 2 (HER2), human trophoblast surface antigen 2 (Trop-2), and other molecules according to antigens that act on the different target. At present, there are three ADCs approved worldwide for the treatment of breast cancer. In addition to trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) for HER2-positive breast cancer, sacituzumab govitecan (SG) is beneficial for triple-negative breast cancer (TNBC). ADCs are effective in the treatment of HER2-positive breast cancer, and also have made important progress in the treatment of advanced TNBC and some HER2 low-expressing breast cancer. These ADCs provide more options for patients with different molecular types of breast cancer.
To observe the effect of vonoprazan quadruple 14-day therapy on Helicobacter pylori (Hp) infection.
A total of 120 Hp positive patients were included and divided into treatment group and control group, 60 cases in each group. The treatment group was given vonoprazan 20 mg + bismuth potassium citrate 220 mg + amoxicillin 1 000 mg+ furazoldone 100 mg, and the control group was given omeprazole 20 mg+ amoxicillin 1 000 mg+ bismuth potassium citrate 220 mg+ furazoldone 100 mg, twice a day for 14 days. The 14C-urea breath test was performed in all patients 4 to 6 weeks after the course of treatment, and the eradication rate of Hp and the occurrence of adverse reactions in the two groups were observed respectively.
Among the 120 patients included, there were 57 males and 63 females, aged from 20 to 69 years old, with an average age of (37.9±5.4) years. The Hp eradication rate in the treatment group was higher than that in the control group (97% vs. 80%, P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05).
Quadruple 14-day therapy with vonoprazan is a safe and highly effective treatment for Hp eradication and can be used as a first- and second-line treatment.
Carvedilol, a β-blocker with the function of blocking α1 and β adrenoceptors, has been widely used in existing clinical practice for cardio vascular diseases, such as hypertension, chronic heart failure and arrhythmia. In recent years, some clinical researches showed that carvedilol might have some potentially novelty prospect on prevention of atherosclerosis, protection of cardiac function of patients with different complications, improvement of diabetic patients’ ability to regulate blood sugar, and treatment of breast cancer and Alzheimer’s disease. Moreover, with the further study of G protein coupled receptor (GPCR), the special mechanism of β-arrestin-biased GPCR signal transduction had been found in carvedilol, Which could contribute to its highly selective action on target cells and could reduce the incidence of adverse drug reactions.
To evaluate the relative risk of respiratory tract disease in rheumatoid arthritis (RA) patients treated with tofacitinib.
From PubMed, Embase, Web of Science, and Cochrane Library databases, the double-blind randomized controlled trials (RCTs) of RA patients who treated with tofacitinib were searched, and the search time limit was from the establishment of the databases to September 2022. The Cochrane risk of bias tool was used to evaluate the quality of the included trials, the RevMan 5.3 software was used for statistical analysis, and the Mantel-Haenszel fixed-effects method was used for relative risk (RR) comparison to evaluate the results.
Fourteen double-blind RCTs were included, with a total of 6 372 RA patients. The results of meta-analysis showed that compared with the control group, the risk of lower respiratory tract infection was significantly increased in the tofacitinib group (RR= 2.32, 95% CI:1.27 to 4.24,P=0.006), while the risk of pulmonary embolism was significantly reduced (RR=0.16, 95% CI:0.03 to 0.94, P=0.04). There was no significant difference in the risk of upper respiratory tract infection, influenza, pneumonia, opportunistic respiratory tract infection, and other non-infectious respiratory adverse events between the tofacitinib group and the control group (P>0.05).
Tofacitinib used for the treatment of RA will increase the risk of lower respiratory tract infection, but has no correlation with the risk of other respiratory tract diseases.