To observe the clinical efficacy and safety of dexmedetomidine injection combined with esketamine injection in the treatment of patients with oral squamous cell carcinoma radical resection.

Patients with oral squamous cell carcinoma radical resection were randomly divided into treatment and control groups. The treatment group will receive intravenous administration of 0.6 μg·kg^-1 dexmedetomidine 10 minutes before anesthesia induction. Subsequently, anesthesia induction will be performed with intravenous administration of 0.5 mg·kg^-1 esketamine. Anesthesia maintenance will be achieved with intravenous infusion of 0.25 mg·kg^-1·h^-1 esketamine and 0.3 μg·kg^-1·h^-1 dexmedetomidine used an infusion pump. The control group will receive intravenous administration of an equivalent volume of 0.9% NaCl 10 minutes before anesthesia induction. Anesthesia induction will then be performed with intravenous administration of 2.5-5.0 μg·kg^-1 fentanyl. Anesthesia maintenance will involve intravenous infusion of 0.10-0.25 μg·kg^-1·min^-1 remifentanil used an infusion pump. The anesthesia effectiveness, analgesic effectiveness, hemodynamics and safety were compared between the two groups.

Treatment group were enrolled 62 cases, 1 case dropped out, and 61 cases were finally included in the statistical analysis. Control group were enrolled 61 cases, 1 case dropped out, and 60 cases were finally included in the statistical analysis. The recovery room stay time of treatment and control groups was (25.97±4.52) and (18.39±3.64) min, the extubation time was (16.75±4.84) and (10.16±3.18) min, and the differences were statistically significant (all P<0.05). After operation 24 h, visual analogue scores of treatment and control groups were (0.85±0.17) and (1.39±0.25) points, adrenocorticotropin levels were (60.07±7.13) and (72.64±9.81) pg·mL^-1, cortisol levels were (481.20±49.15) and (539.94±57.77) nmol·L^-1, and the differences were statistically significant (all P<0.05). The mean arterial pressure at 30 min after anesthesia induction (T1) and at the end of surgery (T2) in treatment group were (82.34±4.98) and (86.57±4.18) mmHg, while those in control group were (77.25±7.16) and (76.02±6.29) mmHg; the heart rates of T1 and T2 in treatment groups were (64.08±4.19) and (66.45±4.83) time·min^-1, while those in control group were (68.44±6.02) and (72.08±7.27) time·min^-1; and the differences were statistically significant (all P<0.05). The adverse drug reactions in two groups were nausea, vomiting, bradycardia and dizziness. The total incidences of adverse drug reactions in treatment and control groups were 8.20% and 15.00%, without significant difference (P>0.05).

Dexmedetomidine injection combined with esketamine injection has a definitive analgesia efficacy in the treatment of patients with oral squamous cell carcinoma radical resection, which can significantly reduce stress responses, maintain hemodynamic stability, without increasing the incidence of adverse drug reactions.

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 investigate the mechanism of Achyranthoside Ⅰ inhibits pyroptosis in chondrocytes through the nuclear factor-κB (NF-κB)/NOD receptor protein structure domain related proteins 3 (NLRP3)/cystine containing aspartate specific proteins-1 (caspase-1) signaling pathway.

Primary mouse chondrocytes were divided into blank group (phosphate buffered solution with the same volume), model group [10 ng·mL^-1 interleukin-1β (IL-1β)], control group (10 ng·mL^-1 IL-1β+20 μmol·L^-1 celecoxib) and experimental group (10 ng·mL^-1 IL-1β+3 μg·mL^-1 Achyranthoside Ⅰ). After 24 hours of intervention, the cell proliferation was measured by cell counting kit 8, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), IL-1 and IL-6 were detected by enzyme-linked immunosorbent assay, the protein expression levels of NF-κB p65, NLRP3 and caspase-1 were detected by Western Blot.

The apoptosis rates in experimental, control, model and blank groups were (13.34±0.61)%, (15.64±1.01)%, (21.81±1.10)% and 0; the SOD levels were (147.03±16.49), (130.09±7.33), (122.03±10.71) and (164.40±22.74) nU·mL^-1; the MDA levels were (6.43±0.71), (7.63±1.01), (8.89±1.84) and (5.69±0.81) nmol·L^-1; the IL-1 levels were (338.69±40.95), (361.78±32.15), (391.44±30.59) and (289.23±25.19) pg·mL^-1; the IL-6 levels were (89.96±8.81), (101.10±11.59), (120.39±14.71) and (60.29±6.03) pg·mL^-1; the relative expression levels of NF-κB p65 were 0.68±0.05, 0.97±0.05, 1.26±0.05 and 0.57±0.05; the relative expression levels of NLRP3 were 0.71±0.08, 1.02±0.10, 1.50±0.06 and 0.31±0.05; the relative expression levels of caspase-1 were 0.70±0.07, 1.29±0.08, 1.66±0.07 and 0.51±0.07, respectively. Compared with the model group, the differences of above indexes were statistically significant in the experimental group (all P<0.05).

Achyranthoside Ⅰ can improve the oxidative stress status induced by IL-1β in chondrocytes, reduce the expression of proteins related to the NF-κB signaling pathway, and thereby decrease the occurrence of caspase-1 dependent pyroptosis, providing a protective effect on chondrocytes.

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 explore the protective effect of resveratrol on myocardial damage caused by sepsis in rats.

Forty SD rats were randomly divided into control group, model group, experimental group and combined group, with 10 rats in each group. Except the control group, the other rats were intraperitoneally injected with 20 mg·kg^-1 lipopolysaccharide, while the control group was injected with the same amount of normal saline. Two hours before modeling, the experimental group and combinated group were given 50 mg·kg^-1 resveratrol by gavage, and the control group and model group were given the same amount of normal saline by gavage. The combined group was injected with 10 nmol of micro RNA-155 (miR-155) agomir through the tail vein, and the other group was injected with equal volume of normal saline through the tail vein. Left ventricular function parameters of rats were measured by echocardiography. The level of myocardial injury markers was detected by colorimetry. Quantitative reverse transcription polymerase chain reaction was used to detect the expression of miR-155. The expression of sirtuin 1 (SIRT1) and related proteins of nuclear factor κB signaling pathway were detected by Western blot.

The left ventricular ejection fraction of control group, model group and experimental group were (80.78±12.85)%, (55.92±7.86)% and (71.55±10.71)%, respectively; left ventricular fractional shortening were (34.08±5.75)%, (22.92±2.96)%, (28.72±4.25)%, respectively; left ventricular end disatolic diameter were (3.12±0.46), (6.34±0.69), (4.95±0.57) mm, respectively; the left ventricular end systolic diameter were (5.98±0.65), (7.24±0.80), (6.16±0.78) mm, respectively; the fractional shortening were (38.91±5.38)%, (22.67±3.53)%, (30.74±3.97)%, and the expression levels of creatine kinase-MB were (661.56±85.44), (1181.41±142.14), (915.02±105.19) U·L^-1, respectively; the expressions levels of cardiac troponin Ⅰ were (148.17±28.48), (448.17±60.34) and (375.44±49.01) ng·mL^-1, respectively. The expression of miR-155 in control group, model group, experimental group and combined group were 1.00±0.12, 3.79±0.45, 1.87±0.23 and 4.03±0.49, respectively; the protein relative expression levels of nuclear factor κB (NF-κB) were 1.00±0.08, 5.04±0.59, 2.73±0.35, 5.58±0.63, respectively; the protein relative expression levels of inhibitor of NF-κB-β were 1.00±0.11, 3.03±0.37, 1.35±0.15 and 2.89±0.34, respectively; the protein relative expressions of inhibitor of NF-κB-α were 1.00±0.13, 0.86±0.08, 1.21±0.18, 0.77±0.09, respectively; the protein relative expression levels of SIRT1 were 1.00±0.16, 0.66±0.07, 0.93±0.14, 0.54±0.06, respectively. The above indicators of the model group were compared with the control group, the experimental group were compared with the model group, and the above indicators of the combined group were compared with the experimental group, and the differences were statistically significant (all P<0.05).

Resveratrol can alleviate myocardial injury and improve cardiac function in sepsis rats, which may be achieved by down-regulating the expression of miR-155, up-regulating the level of SIRT1, and inhibiting the nuclear factor κB signaling pathway.

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.

To explore the pharmacokinetic (PK) characteristics of desloratadine tablets and reference drugs in healthy subjects, and evaluate their bioequivalence and safety.

The random, open, two-period, cross-over pharmacokinetic study method was adopted, each subject received a single oral dose of desloratadine tablets test drug(T) or reference drug(R) for 5 mg. The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS); and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.

The main PK parameters of T and R of desloratadine were as follows: the fasting condition C_max were respectively (3 809.82±1 016.54) and (3 642.36±777.07) pg·mL^-1; AUC_0-120h were respectively (5.75×10⁴±5.03×10⁴) and (5.51×10⁴±4.00×10⁴) pg·h·mL^-1; AUC_0-∞ were respectively (6.85×10⁴±1.03×10⁴) and (6.37×10⁴±7.92×10⁴) pg·h·mL^-1. The fed condition C_max were respectively (4 398.98±1 191.22) and (4 744.40±1 511.97) pg·mL^-1; AUC_{0-120 h} were respectively(5.25×10⁴±1.82×10⁴) and (5.55×10⁴±1.98×10⁴) pg·h·mL^-1; AUC_0-∞ were respectively(5.37×10⁴±1.86×10⁴) and (5.68×10⁴±2.04×10⁴) pg·h·mL^-1. The 90% confidence interval of C_max, AUC_0-t and AUC_0-∞ of desloratadine were all within 80.00%~125.00%.

There was no significant difference in the main PK parameters between T and R under fasting or high-fat postprandial conditions, and desloratadine tablets were bioequivalent, safe and well tolerated.

To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.

A single-center, randomized, open, two-agent, two-sequence, four-cycle, fully repeated crossover, single-dose trial design was used in this study, healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state, and blood samples were taken at different time points, respectively. The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.

The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows: C_max were (339.63±156.47) and (318.86±132.13) ng·mL^-1; t_1/2 were (2.34±0.68) and (3.60±2.40) h; AUC_0-t were (556.62±251.65) and (528.50±201.78) ng·mL^-1·h; AUC_0-∞ were (563.39±255.69) and (535.15±203.24) ng·mL^-1·h; t_max were 3.65 and 6.99 h. After high-fat diet, the C_max and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased, C_max decreased by 6.12%, AUC_0-t decreased by 5.05%, AUC_0-∞ decreased by 5.01%, and t_max was delayed by about 3.34 h. C_max, AUC_0-t and AUC_0-∞90% confidence interval were 73.13%-115.10%, 83.22%-112.28% and 83.40%-112.13%, respectively. Neither was between 85.00%-125.00%.

High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated, so it is suitable to be administered on an empty stomach.

To establish a ultra-high performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method for determining the concentration of sotagliflozin in rat plasma and apply it to pharmacokinetic studies in rats.

Electrospray negative ion multi-reaction ion detection was used. Chromatographic column: EXT-C₁₈ (2.1 mm×100.0 mm, 2.7 μm); column temperature: 45 ℃; mobile phase: 5 mmol·L^-1 ammonium acetate aqueous solution-acetonitrile; flow rate: 0.35 mL·min^-1; ion pairs: sotagliflozin m/z 483.3→315.1, dapagliflozin m/z 467.4→329.2; injection volume: 6 μL, plasma samples were processed using methyl tert-butyl ether liquid-liquid extraction. Six male SD rats were administered a single oral dose of sogliflozin at 40 mg·kg^-1, and detected the concentration of sogliflozin in plasma. Pharmacokinetic parameters were calculated using Drug And Statistics (DAS) 2.1.1.

Sotagliflozin showed good linearity within the range of 5-2 000 ng·mL^-1, with intra-day and inter-day precision both less than 15%. The recovery rate, matrix effect, and stability were all within the specified range. Pharmacokinetic parameters: C_max was (3 716.67±568.28) ng·mL^-1, t_max was (1.00±0.32) h, t_1/2 was (2.28±0.45) h, AUC_0-t was (1.70×10⁴±2 075.87) ng·mL^-1·h.

This study established a method for determining the concentration of sotagliflozin in rat plasma, which is characterized by high sensitivity, rapid detection, and good repeatability. It is suitable for the determination of sotagliflozin concentration in plasma and pharmacokinetic studies.

To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.

This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S. Food and Drug Administration (FDA) from 2005 to 2022, included the drugs mentioned in the QT interval prolongation risk, analyzed the clinical research and QT research results, and sorted out the identification and warning rules of the instructions.

A total of 35 drugs were included, 4 drugs wrote the risk of QT interval prolongation in the black box warning, 21 drugs were wrote in the warning and precautions position, 6 drugs were wrote in the adverse reaction section, and 2 drugs were only described under clinical pharmacology section. According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences, they were displayed in the warnings (black box warnings), precautions (warnings and precautions) and adverse reactions in the instructions.

The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments. It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research, and continue to carry out safety monitoring and update the instructions in time after listing.