Latest ArticlesWhether in vivo gene therapy products or in vitro gene-modified cell therapy products, the risk of gene insertion and mutation of integration in the gene modification safety evaluation are all key contents of concern. With the development of high-throughput sequencing and bioinformatics analysis technology, integrated site detection and analysis have been able to provide important information for understanding and judging risk. However, the safety prediction has not been achieved ideally. One of the core challenges is the methodological development of integration sites detection. On the one hand, it is the technical limitation of the assays, on the other hand, there is no public technical standard for the assays. In this paper, the commercial integration site detection technologies in safety evaluation of cell and gene therapy products are introduced. The challenges and future solutions are also discussed.
Non-coding RNA (ncRNA), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB) signaling pathways are involved in the interaction between ncRNA, Nrf2 and NF-κB, the mechanism that regulates blood lipids and anti-atherosclerosis. ncRNA, including microRNA (miRNA), small interfering RNA (siRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA), are potential drug targets in the study of lipid regulation and anti-atherosclerosis drugs. Nrf2-NF-κB signaling pathway is an important pathway for regulating oxidative stress and inflammatory responses, regulating lipid levels and reducing the risk of cardiovascular diseases such as atherosclerosis. In addition, ncRNA, as an important regulatory molecule, can regulate oxidative stress and inflammation by regulating Nrf2-NF-κB signaling pathway, thus play an important role in regulating blood lipids and anti-atherosclerosis. This paper reviews the current research and development status of ncRNA-Nrf2-NF-κB signaling pathway in the field of lipid-regulating anti-atherosclerotic drugs, including drugs currently on the market and drugs under development, in order to provide new ideas and directions for the prevention and treatment of cardiovascular diseases such as atherosclerosis.
Pyroptosis plays an important role in the development of rheumatoid arthritis (RA) and the molecules involved in the pyroptosis pathway can influence the course of RA. Therefore, inhibition of pyroptosis may be an effective therapeutic strategy to slow down the development of RA. In this paper, we systematically reviewed the relationship between pyroptosis and RA, explored the mechanism of pyroptosis in RA from three aspects: nucleotide oligomerisation structural domain-like receptor protein 3 inflammatory vesicles, Gasdermin family of proteins and inflammatory cytokines, and revealed how the relevant molecules in the pyroptosis pathway contribute to inflammatory responses and intercellular signalling, thereby exacerbating the progression of RA. The aim of this review is to provide a theoretical basis for the study of the pathological mechanisms of RA and the development of therapeutic drugs for RA that target the inhibition of pyroptosis.
Obesity is a ‘key’ component that contributes to the further development of type 2 diabetes mellitus (T2DM). Adipose tissue releases adipokines that act on the cardiovascular system in an endocrine and paracrine manner, different adipokines have different effects. Pro-inflammatory adipokines exacerbate inflammatory responses and oxidative stress in cardiomyocytes, leading to myocardial hypertrophy and interstitial fibrosis, inducing heart failure. Anti-inflammatory adipokines protect against high glucose-induced vascular endothelial dysfunction and delay the development of cardiovascular complications in T2DM by inhibiting endoplasmic reticulum stress, oxidative stress and increasing nitric oxide production. Balancing the roles played by pro-inflammatory and anti-inflammatory adipokines in diabetic cardiomyopathy (DCM) is crucial. In this paper, we will study the effect of obesity-associated adipokines in DCM, summarise novel glucose-lowering drugs in the clinic that can both reduce body weight and benefit the heart, and provide a theoretical basis for preventing and treating the development of obesity-combined DCM.
After the occurrence of complications in diabetes mellitus (DM) patients, the condition will be aggravated, resulting in sustained effects on multiple tissues and organs in the body, thus many complications. Chronic kidney disease (CKD) and cardiovascular disease (CVD) are major complications of type 2 diabetes mellitus (T2DM), increasing the risk of cardiovascular and all-cause death. Current therapeutic agents that delay the progression of CKD and CVD include angiotensin-converting enzyme inhibitors, angiotensin Ⅱ receptor blockers, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and salocorticoid receptor antagonists, etc. Although the use of these drugs can delay the progression of macrovascular and microvascular complications in patients with diabetes, T2DM patients with CKD are still at high risk of CVD. This review explores the relationship between CKD and CVD in T2DM patients, in order to provide evidence for clinical treatment.
Low density lipoprotein cholesterol (LDL-C) is a pathogenic risk factor for atherosclerotic cardiovascular disease (ASCVD), so domestic and international guidelines recommend strict management of its level. Statins are the cornerstone of lipid-lowering therapy, however, some patients are still unable to achieve LDL-C target with moderate doses of statins. There is a 6% effect of statins, so combination with a novel lipid-lowering drugs is needed. Proprotein convertase chymotrypsin 9 (PCSK9) inhibitors are currently novel lipid-lowering drugs, which further reduce LDL-C levels in plasma by lowering the level or inhibiting the function of PCSK9 in vivo, thus playing a role in regulating blood lipids and reversing atherosclerotic plaques. The PCSK9 inhibitors currently used in clinical application in China include eloeu monoclonal antibody, aliskiren monoclonal antibody and inksilan, etc. This article briefly describes the classification of PCSK9 inhibitors and related clinical studies and summarizes the current research status of PCSK9 inhibitors in regulating blood lipids and affecting atherosclerotic plaques.
To analyze the clinical characteristics of patients infected with emphysematous pyelonephritis (EPN) and the drug resistance of the strains. To enhance the understanding of EPN, provide a basis for the selection of antibacterial drugs in clinical practice.
Evaluated 15 EPN patients’ clinical characteristics and outcome, analysis of pathogenic bacteria and drug resistance.
Among the 15 EPN patients, 66.67% (10 cases/15 cases) patients were cured, 13.33% (2 cases/15 cases) patients died, and 20.00% (3 cases/15 cases) patients were adverse. Fluid cultures identified 12 strains of pathogenic bacteria, with Escherichia coli being the most prevalent (66.67%, 8 cases/12 cases), followed by Klebsiella pneumoniae (25.00%, 3 cases/12 cases), and Pseudomonas aeruginosa was the least common (8.33%, 1 cases/12 cases), 75.00% (9 cases/12 cases) of the strains were multi-drug resistant. The drug sensitivity test results showed that amikacin, cefotetan, and cefoperazone sulbactam were 100.00% sensitive antibiotics; the sensitivity rates of meropenem, imipenem, and ertapenem were 91.67%.
Patients with EPN have high mortality and poor prognosis. Escherichia coli was the most common pathogenic bacteria, followed by Klebsiella pneumoniae, and the proportion of multi-drug resistant strains was high. We recommend the use of over 90% of the pathogen-sensitive drugs with susceptibility about 90% identified in this study.
To observe the clinical efficacy and safety of different doses of atorvastatin calcium tablets combined with trimetazidine hydrochloride tablets in the treatment of patients with chronic heart failure (CHF).
CHF patients were randomly assigned to low-dose group, high-dose group and control group using a digital randomization method. The control group received conventional heart failure treatment in addition to trimetazidine hydrochloride tablets (20 mg per dose, tid). The low-dose group received conventional atorvastatin calcium tablets (20 mg per dose, qd) on basis of the treatment given to the control group. The high-dose group received higher dose of atorvastatin calcium tablets (40 mg per dose, qd) in addition to the treatment for the control group. All treatment continued for 3 months. The clinical efficacy, heart function indicators, three-dimensional myocardial fibrosis parameters, myocardial cell apoptosis-related factors and safety were compared among the three groups.
A total of 8 cases were dropped during the trial, and 30 cases were included in the low-dose group, 24 cases in the high-dose group, and 26 cases in the control group. After treatment, the efficacy rates were 76.67% (23 cases/30 cases) for the low-dose group, 91.67% (22 cases/24 cases) for the high-dose group, and 61.54% (16 cases/26 cases) for the control group. The difference between the high-dose group and the control group was statistically significant (P<0.05). After treatment, the left ventricular ejection fractions for the low-dose group, high-dose group and control group were (52.25±2.11)%, (55.34±2.76)% and (48.72±2.48)%, respectively; the left ventricular end-diastolic diameters were (51.33±3.94), (48.63±4.79) and (55.79±4.85) mm, respectively; the left ventricular end-systolic diameters were (39.77±3.53), (36.72±3.29) and (42.78±3.69) mm, respectively; troponin Ⅰ levels were (1.62±0.33), (1.36±0.29) and (1.84±0.36) ng·L-1, respectively; N-terminal pro B-type natriuretic peptide levels were (797.25±79.32), (749.20±84.65) and (854.15±90.57) pg·mL-1, respectively; global strain values were -29.87±5.19, -32.96±5.82 and -26.33±5.46, respectively; cell membrane receptor protein levels were (2.55±0.46), (2.30±0.36) and (2.84±0.50) μg·L-1, respectively; soluble Fas ligand levels were (0.23±0.06), (0.19±0.04) and (0.28±0.09) μg·L-1, respectively; the differences among the three groups and between each pair of groups for the above indicators were statistically significant (P<0.05, P<0.01, P<0.001). The main adverse drug reactions in the low-dose group were gastrointestinal bloating and constipation, while the high-dose group primarily experienced constipation. The control group mainly reported nausea. The incidences of adverse drug reactions in the low-dose, high-dose and control groups were 6.67%, 4.17% and 3.85%, respectively, without statistically significant differences (all P>0.05).
The curative effect of intensive dose atorvastain calcium tablets combined with trimetazidine hydrochloride tablets in the treatment of CHF is better than that of conventional dose atorvastatin combined with trimetazidine hydrochloride tablets, and the safety is good.
To observe the analgesic effects and safety of flurbiprofen axetil injection combined with dezocine injection in postoperative patient-controlled intravenous analgesia (PCIA) for patients with intertrochanteric femoral fractures (IFF).
IFF patients were divided into control group and treatment group based on cohort method. The control group was given 0.5 mg·kg-1 dezocine injection diluted with 100 mL of 0.9% NaCl and then injected with analgesic pump. The treatment group was given 1.0 mg·kg-1 flurbiprofen axetil injection + 0.3 mg·kg-1 dezocine injection diluted with 100 mL of 0.9% NaCl and then injected with analgesic pump Postoperative visual analog scale (VAS), Ramsay sedation score (RSS), mini-mental state examination (MMSE), hemodynamic parameters (heart rate, mean arterial pressure), and safety evaluations were compared between the two groups.
A total of 67 patients were enrolled in the control group; and 53 patients were enrolled in the treatment group. Postoperative VAS scores at 2, 12 and 24 h were (1.95±0.39), (2.52±0.31) and (2.21±0.40) points in the treatment group, and (2.47±0.44), (3.17±0.34) and (2.76±0.37) points in the control group. RSS scores at the same time were (3.15±0.33), (3.39±0.35) and (3.72±0.46) points for the treatment group, and (2.79±0.54), (3.16±0.43) and (3.28±0.68) points for the control group. MMSE scores at 1, 3, and 7 days postoperatively were (25.08±2.40), (26.80±2.01) and (27.64±2.59) points in the treatment group, and (22.36±2.24), (24.53±2.25) and (25.37±1.84) points in the control group. Thirty minutes after surgery, the heart rate was (86.61±4.80) beat·min-1 in the treatment group and (82.74±4.17) beat·min-1 in the control group, while the mean arterial pressure was (74.28±4.49) mmHg and (71.76±3.42) mmHg, respectively. These indicators in the treatment group showed statistically significant differences compared to the control group (all P<0.05). The main adverse drug reactions in the treatment group were dizziness, fatigue, drowsiness, and nausea/vomiting, while the control group also had respiratory depression in addition to dizziness, fatigue, drowsiness, and nausea/vomiting. The total incidence of adverse drug reactions was 7.55% (4 cases/53 cases) in the treatment group and 20.90% (14 cases/67 cases) in the control group, with statistically significant difference (P<0.05).
Flurbiprofen axetil injection combined with dezocine injection for postoperative PCIA in IFF patients provides superior analgesic and sedative effects compared to dezocine monotherapy, enhances cognitive function, stabilizes hemodynamics, and has good safety.
To observe the clinical efficacy and safety of general anesthesia induction with different doses of remimazolam in the vascular interventional treatment of intracranial aneurysms, and observe the safety.
The patients with intracranial aneurysms who will receive vascular interventional treatment for intracranial aneurysms were divided into low-dose group (0.2 mg·kg-1 remimazolam), middle-dose group (0.3 mg·kg-1 remimazolam) and high-dose group (0.4 mg·kg-1 remimazolam) according to cohoert. The three groups completed intravenous injection of 0.2-0.4 mg·kg-1 remimazolam. When the consciousness of patients disappeared, 10 μg·kg-1 alfentanil and 0.2 mg·kg-1 cisatracurium besilate were used for anesthesia induction, and 0.3-1.0 mg·kg-1·h-1 remimazolam+ 0.1 μg·kg-1·min-1 remifentanil + 0.2 mg·kg-1·h-1 cisatracurium besilate were applied for anesthesia maintenance. The anesthetic effect, heart rate (HR) and mean arterial pressure (MAP) during recovery period, oxidative stress indexes at different time points and, remimazolam remedy were compared among the three groups, and the safety was evaluated.
There were 27 cases in low-dose group, 28 cases in middle-dose group and 25 cases in high-dose group. The HR values at extubation in low-dose group, middle-dose group and high-dose group were (79.47±6.85), (75.84±6.71) and (72.03±5.79) beat·min-1, HR values at 5 min after extubation were (81.92±6.59), (78.09±7.03) and (74.17±7.26) beat·min-1, serum superoxide dismutase (SOD) levels at 24 h after surgery were (87.61±11.25), (95.49±14.02) and (103.86±15.37) U·mL-1, serum malondialdehyde (MDA) levels were (19.69±2.74), (17.24±2.45) and (15.08±2.29) mmol·L-1, serum catalase (CAT) levels were (66.75±8.39), (71.69±8.55) and (76.91±9.13) U·mL-1, the onset time of sedation was (94.36±4.42), (82.29±4.15) and (75.17±5.38) s, respectively, and there were significant differences between any two groups of the three groups (all P<0.05). There were 4 cases (14.81%), 0 case and 0 case of remimazolam remedy in low-dose group, middle-dose group and high-dose group, respectively, and the index in middle-dose group and high-dose group was significantly different compared with that in low-dose group (P<0.05). In the low-dose group, there was 1 case (3.70%) of hypotension, 1 case (3.70%) of respiratory depression, and 2 cases (7.41%) of intraoperative body movement. In the middle-dose group, there was 1 case (3.70%) of hypotension, 1 case (3.57%) of bradycardia, and 1 case (3.70%) of respiratory depression. In the high-dose group, there was 1 case (4.00%) of hypotension, 2 cases (8.00%) of bradycardia, and 2 cases (8.00%) of respiratory depression. There was no statistically significant difference in the incidence of adverse drug reactions among the three groups (all P>0.05).
The induction of general anesthesia with different doses of remimazolam has a certain application effect in the vascular interventional treatment of intracranial aneurysms, and the induction of general anesthesia with high doses of remimazolam (0.4 mg·kg-1) is the most ideal. It is not only beneficial to maintaining the stability of hemodynamics during the recovery period, and alleviating the oxidative stress response, but also shortening the onset time of sedation, reduce the number of remedial cases, and it has good safety.
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