Latest ArticlesThe phosphatidy linositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway promotes the occurrence and development of endometriosis (EMs) by participating in angiogenesis and cell invasion. In recent years, with the deepening of pharmacological research, traditional Chinese medicine (TCM) has been widely recognized for its advantages of multi-targets, multi-pathways, and fewer adverse drug reactions, and the research on the treatment of EMs by TCM through the modulation of the PI3K/Akt signaling pathway has also achieved certain results. Based on this, this paper analyzes the roles of single Chinese medicine, Chinese medicinal compound and TCM therapeutic methods in regulating the PI3K/Akt signaling pathway in the treatment of EMs, with the aim of providing a theoretical basis for the treatment of EMs by TCM.
Ciprofol is a type of innovative drug independently developed in China and with global independent intellectual property rights. It is a short-acting intravenous sedative based on the structural modification of propofol. It has the advantages of fast onset, fast recovery, high titer, good selectivity, low accumulation, stable respiratory circulation, and few adverse reactions, providing a better choice for clinical stable sedation and anesthesia, and has good clinical application potential. A series of clinical studies have evaluated the sedative effects of ciprofol in various procedures and settings, demonstrating its application in endoscopic sedation, general anesthesia, and sedation during intensive care. This paper reviewed the mechanism of action, pharmacokinetics and pharmacokinetic properties of ciprofol, and the progress of clinical application research, and evaluated the effectiveness and safety of ciprofol by synthesizing relevant clinical trial data.
Testing for carcinogenicity is a key toxicological test that supports marketing authorization and an important part of nonclinical safety studies for pharmaceuticals. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) S1B “Testing for carcinogenicity of pharmaceuticals” provides recommendations on approaches for evaluating the carcinogenic potential of pharmaceuticals which can include the conduct of a 2-year rat carcinogenicity study. With the application of the ICH S1B (R1) “Addendum to testing for carcinogenicity for pharmaceuticals” in China, sponsors are allowed to use the weight of evidence (WoE) method rather than the conventional 2-year rat carcinogenicity study, a more scientific and comprehensive assessment of the carcinogenic potential of certain molecules specified in ICH S1A “Guideline on the need for carcinogenicity studies of pharmaceuticals”. This addendum identifies key factors supporting WoE assessment and emphasizes the importance of survey investigative studies and emerging technology in assessing human carcinogenic risks. This article discusses the background information on the development of ICH S1B (R1), main technical issues, and follow-up work, in order to facilitate the understanding and implementation of this guideline.
To observe the clinical efficacy and safety of escitalopram oxalate tablets combined with levodopa and benserazide hydrochloride tablets in the treatment of patients with Parkinson’s disease.
The patients with Parkinson’s disease were randomly divided into control group and treatment group. The control group received levodopa and benserazide hydrochloride tablets 125 mg per time, tid, orally. On the basis of control group, the treatment group received escitalopram oxalate tablets 10 mg per time, qd, orally. Two groups were treated for 3 months. The clinical efficacy, Montreal cognitive assessment (MoCA) scores, Hamilton depression rating scale (HAMD) scores, unified Parkinson’s disease rating scale (UPDRS) scores, the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and nerve growth factor (NGF), and safety were compared between two groups.
Treatment group was enrolled 116 cases, 4 cases dropped out, and 112 cases were finally included in the statistical analysis. Control group was enrolled 116 cases, 2 cases dropped out, and 114 cases were finally included in the statistical analysis. After treatment, the total effective rates of treatment and control group were 82.14% (92 cases / 112 cases) and 65.79% (75 cases / 114 cases), with significant difference (P<0.05). After treatment, the MoCA scores of treatment and control groups were (24.89±2.87) and (19.58±2.62) points, the HAMD scores were (10.45±1.06) and (15.84±1.49) points, the UPDRS scores were (40.06±5.28) and (47.78±5.52) points, the IL-6 levels were (4.12±0.63) and (6.71±1.13) mg·L-1, the TNF-α levels were (8.71±1.64) and (11.14±2.05) mg·L-1, the NGF levels were (41.56±5.20) and (30.47±4.14) ng·mL-1, respectively. The differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of treatment group were somnolence and nausea/vomiting, while those in control group were nausea/vomiting and constipation. The total incidences of adverse drug reactions in treatment and control groups were 15.18% and 12.28%, without statistically significant difference (P>0.05).
Escitalopram oxalate tablets combined with levodopa and benserazide hydrochloride tablets significantly improves clinical efficacy in the treatment of patients with Parkinson’s disease, which can significantly ameliorate the inflammatory responses and neurotrophic factor levels, without increasing the incidence of adverse drug reactions.
To evaluate the efficacy and safety of Morinda officinalis oligoes (MOs) capsules in the 24-week maintenance phase treatment of mild and moderate depression.
This study was the maintenance phase part of phase Ⅳ clinical trial for MOs capsules. Patients who was diagnosed as mild or moderate depressive episode were included into this study. Participants who were finished MOs capsules’ 8-week acute phase and 24-week continuation phase would go on to take MOs capsules for 24 weeks. During the acute phase, patients would take the start treatment dosage MOs capsules 300 mg qd for 2 weeks. On the final of week two, if HAMD-17 reduce rate <30%, patients would take an increased dosage treatment about MOs capsules 600 mg qd, and if HAMD-17 reduce rate ≥30%, patients would continue the start treatment dosage. The dosage remained unchanged during the first 16 weeks in maintenance phase, and from week 17 to week 24 the dosage would be cut to the half. The changes from baseline to endpoint of Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Clinical Global Impression-Severity (CGI-S) and Arizona Sexual Experience Scale (ASEX) were evaluated, and recovery rate, relapse rate, relapse time were reported. The incidence of adverse events was reported.
The scores of HAMA at baseline and after treatment were (3.64±2.51) and (2.84±2.60) points, the difference was statistical significant (P<0.05). The scores of HAMD-17 at baseline and after treatment were (4.00±2.13) and (3.90±4.09) points, CGI-S were (1.02±0.51) and (0.90±0.79) points, scores of ASEX were (16.15±5.65) and (15.95±5.70) points, the differences were not statistical significant (P>0.05). After 24-week’s treatment, the recovery rate was 84.21% (96 cases/114 cases), the relapse rate was 6.14% (7 cases/114 cases), the relapse time was (82.14±39.66) d. The incidence of treatment-related adverse events was 33.05% (39 cases/118 cases).
MOs capsules can be used for the maintenance treatment of mild or moderate depression, and were well tolerated and safe.
To analyze the effect of insulin degludec/insulin aspart injection combined with metformin extended-release tablets on insulin resistance in patients with type 2 diabetes mellitus (T2DM).
T2DM patients were divided into control group and treatment group using a cohort method. The control group received oral metformin extended-release tablets (0.5 g, tid) and subcutaneous injections of insulin glargine injection (10 U, qd), while the treatment group received oral metformin extended-release tablets (0.5 g, tid) and subcutaneous injections of insulin degludec/insulin aspart injection (0.1-0.2 U·kg-1·d-1, evenly divided before breakfast and dinner). Both groups were treated for 12 weeks. The efficacy, blood glucose control [fasting blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin A1c(HbA1c)], insulin function [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment-β (HOMA-β)]were compared, and safety was evaluated.
A total of 49 cases were enrolled in the treatment group and 51 cases in the control group. The overall effective rates in the treatment and control groups were 93.88% (46 cases/49 cases) and 80.39% (41 cases/51 cases), respectively, showing a statistically significant difference (P<0.05). After treatment, the fasting blood glucose levels in the treatment and control groups were (5.83±0.79) and (6.53±0.81) mmol·L-1; the 2-hour postprandial blood glucose levels were (7.73±0.86) and (8.41±0.97) mmol·L-1; HbA1c levels were (6.34±0.88)% and (6.80±0.92)%; FINS levels were (6.02±1.13) and (7.13±1.04) mU·L-1; HOMA-IR values were 1.56±0.20 and 2.07±0.23; HOMA-β values were 51.67±3.18 and 47.06±3.31, respectively, with all differences being statistically significant (all P<0.05). The adverse drug reactions in the treatment group mainly included hypoglycemia, nausea, dizziness, and diarrhea, while the adverse drug reactions in the control group mainly included hypoglycemia and nausea. The incidence of adverse drug reactions was 10.20% (5 cases/49 cases) in the treatment group and 11.76% (6 cases /51 cases) in the control group, with no statistically significant difference (P<0.05).
The combination of insulin degludec/insulin aspart injection and metformin extended-release tablets can improve insulin resistance and regulate blood glucose levels in T2DM patients, with good safety profiles.
To compare the clinical efficacy and safety of sodium bicarbonate ringer’s injection and 0.9% NaCl as resuscitation fluid in the treatment of patients with diabetic ketoacidosis (DKA).
Patients with DKA were randomly divided into treatment group and control group. After enrollment, the treatment group was immediately given sodium bicarbonate ringer’s , and the control group was given 0.9% NaCl for fluid resuscitation. Other treatment protocols for DKA were the same in two groups. The incidence of hyperchloremia in 96 hour the change value of chloride in 96 hours (with the maximum value minus the baseline value), the total volume of fluid administered over 24 hours, the volume of urine produced over 24 hours, and the incidence of acute kidney injury(AKI) were compared between the two groups. Additionally, the incidence of hypokalemia in the two groups during the 96-hour observation period was recorded, and the safety of the intervention was evaluated.
The study cohort comprised 20 cases in the treatment group, of whom two were dislodged, finally 18 cases were included in the statistical analysis. In the control group, 20 cases were enrolled, with one case being dislodged, leaving 19 cases included in the statistical analysis. The incidence of 96 hour hyperchloraemia in the treatment group and the control group was 27.78% (5 cases/18 cases) and 73.68% (14 cases/19 cases), respectively. Furthermore, the change values of chloride in 96 hour were 11.05(9.30, 13.13) and 19.10(14.10, 29.10) mmol·L-1, respectively. Notably, the differences between the two groups were statistically significant(all P<0.05). The total fluid volume was 3 410.00 and 3 600.00 mL, the 24 hour urine output was 2 075.00 and 2 950.00 mL, and the incidence of AKI was 0% (0 cases/18 cases) and 5.26% (1 cases/19 cases) in the treatment group and the control group, respectively. No statistically significant differences were observed in any of the statistical comparisons(all P>0.05). However, the incidence of hypokalaemia in the treatment group(22.22%) was lower than that in the control group(57.89%), and this difference was statistically significant (P<0.05).
The administration of sodium bicarbonate ringer’s injection for the resuscitation of patients with diabetic ketoacidosis has been demonstrated to reduce the incidence of hyperchloremia at 96 hours, and have good safety.
To investigate the effects of baicalein on apoptosis and immune escape of laryngeal carcinoma cells and its mechanism.
Human laryngeal carcinoma TU686 cells were randomly divided into control group(routine culture), baicalein group (50 μmol·L-1 baicalein), Vector group (transfected with Vector+50 μmol·L-1 baicalein) and CD47 group [transfected with differentiation cluster 47(CD47) +50 μmol·L-1 baicalein]. Cell proliferation and apoptosis were detected by 5-acetylidene-2′-deoxyuridine (Edu) method and Annexin V-FITC/PI double staining method. The expression of proliferative and apoptotic proteins were detected by Western blot. Human peripheral lymphocytes were co-cultured with cells in each group to detect the killing rate of TU686 cells. The phagocytosis rate of TU686 cells was observed.
The Edu positive cell rates in control group, baicalein group, Vector group and CD47 group were (36.24±2.74)%, (13.33±1.93)%, (14.22±1.48)% and (27.80±2.74) %, respectively; the apoptosis rates were (3.94±0.40)%, (28.40±1.76)%, (26.60±1.41)% and (12.33±0.84)%, respectively; the relative expressions of CD47 protein were 1.00±0.11, 0.42±0.07, 0.44±0.06 and 1.21±0.12, respectively; the relative expression levels of CyclinD1 protein were 0.86±0.08, 0.37±0.05, 0.36±0.04 and 0.74±0.08, respectively; the relative expression levels of cleaved cysteine aspartate proteinase-7(Cl-Caspase-7) protein were 0.35±0.04, 0.99±0.12, 1.00±0.11 and 0.50±0.06, respectively; the killing rates of human peripheral lymphocytes to TU686 cells (1∶1 ratio) were (10.61±1.19)%, (32.02±2.27)%, (31.86±2.06)% and (14.39±1.07)%, respectively; the phagocytosis rates were (6.35±0.71)%, (11.99±1.64)%, (12.03±0.76)% and (7.06±0.57)%, respectively. The above indicators, baicalein group compared with the control group, Vector group compared with CD47 group, the differences were statistically significant (P<0.05, P<0.01, P<0.001).
Baicalein may induce the apoptosis of laryngeal carcinoma cells and inhibit the immune escape of laryngeal carcinoma cells by inhibiting the expression of CD47, thus slowing down the progression of laryngeal carcinoma.
Study on the long non-coding RNA (lncRNA) LINC00922 regulating secreted frizzled related protein 1 (SFRP1) to inhibit the malignant progression of human oral mucosal fibroblasts (hOMF) induced by arecoline.
Cells were divided into blank control (NC) group (hOMF cells were not treated in any way), model group (60 mg·L-1 arecoline treatment), oe-LINC02147 group (60 mg·L-1 arecoline treatment, transfected with overexpression of LINC02147 vector), si-SFRP1 group (60 mg·L-1 arecoline treatment, transfected with overexpression of LINC02147 vector, transfected with SFRP1 inhibitor vector). Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of SFRP1 mRNA in each group of cells; immunofluorescence was used to detect the positive expression of alpha-smooth muscle actin (α-SMA) and vimentin in each group of cells; 5-ethynyl-2′-deoxyuridine was used to detect the proliferation rate of each group of cells; dichlorodihydrofluorescein diacetate fluorescence probe method was used to detect the content of reactive oxygen species (ROS) in each group of cells.
The relative expression levels of SERP1 mRNA in model group and oe-LINC02147 group were 1.00±0.08 and 3.75±0.59, respectively; the cell proliferation rates of NC group, model group, oe-LINC02147 group and si-SFRP1 group were (43.61±6.97)%, (12.98±4.27)%, (38.66±5.12)% and (15.73±5.42)%, respectively; ROS content were (9.42±1.73)%, (36.58±6.16)%, (12.89±2.08)% and (33.45±5.76)%, respectively; α-SMA positive expression were 1.00±0.13, 5.02±1.46, 2.36±0.48 and 4.37±0.97, respectively; the positive expressions of vimentin were 1.00±0.15, 4.63±1.51, 1.98±0.85 and 3.92±1.36, respectively. The above indexes in the model group were compared with the NC group, the above indexes in the oe-LINC02147 group were compared with the model group, and the above indexes in the si-SFRP1 group were compared with the oe-LINC02147 group, and the differences were statistically significant (all P<0.001).
LINC02147 may inhibit the malignant progression of arecoline-induced human oral mucosa fibroblasts by regulating SFRP1.
To investigate the role of miRNA-633 in targeting the regulation of bone morphogenetic protein (BMP) and Smad protein pathways in promoting the proliferation and differentiation of dental pulp stem cells into dentin.
Human dental pulp stem cells were randomly divided into control, ov-miRNA-633, NC, anti-miRNA-633 and cotransfection groups. The ov-miRNA-633 and control groups were transfected with miRNA-633 overexpression vector and corresponding control blank vector, respectively. The anti-miRNA-633 and NC groups were transfected with miRNA-633 knockout vector and corresponding control blank vector, respectively. The cotransfection group was transfected with miRNA-633 overexpression vector + shRNA-N-Cadherin. Cell proliferation was detected by CCK-8 method. The expression levels of N-Cadherin were detected by real-time polymerase chain reaction. The expression levels of phosphorylated Smad 1/5/8 (p-Smad 1/5/8) were detected by Western blotting.
The optical density values on the 7th day of the control, ov-miRNA-633, NC, anti-miRNA-633 and cotransfection groups were 1.65±0.05, 1.79±0.08, 1.55±0.05, 1.19±0.08 and 1.76±0.07; the relative expression levels of N-Cadherin mRNA were 1.09±0.03, 0.63±0.03, 1.06±0.04, 1.31±0.09 and 0.46±0.06; the relative expression levels of p-Smad 1/5/8 protein were 0.79±0.05, 1.28±0.08, 0.80±0.09, 0.62±0.06 and 1.09±0.18, respectively. The differences of above indexes were statistically significant between the ov miRNA-633 group and the control group (P<0.05, P<0.01). And the differences of above indexes were statistically significant between the cotransfection group and the anti miRNA-633 group (all P<0.05).
miRNA-633 could promote the proliferation and differentiation of dental pulp stem cells into dentin by inhibiting N-cadherin expression, activating the BMPs/Smad pathway.