To investigate and analyze the adverse drug event (ADE) signals associated with ceftriaxone in children in the real world, and provide references for the safety evaluation of ceftriaxone in children.

ADE reports in the US FDA Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2022 involving children aged 0-17 years with ceftriaxone as the primary suspected drug were extracted. ADEs were classified into organ systems using the Medical Dictionary for Regulatory Activities (MedDRA). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were utilized to identify ADE signals associated with ceftriaxone.

A total of 999 ADE reports were collected for children aged 0-17 years with ceftriaxone as the primary suspected drug. There were 139 related ADE signals affecting 18 organ systems. The top 3 ADEs in terms of frequency were acute kidney injury, cholelithiasis, and postrenal acute renal failure. The top 3 ADEs in terms of signal strength were postrenal acute renal failure, ureteral calculus, and intravascular hemolysis. The top 10 ADEs in terms of signal strength for ceftriaxone in different age groups of children primarily involved the hepatobiliary system, renal and urinary system, and the blood and lymphatic system. After the update of the ceftriaxone package insert in July 2007, the proportion of pediatric stone-related ADEs caused by ceftriaxone decreased from 5.88% to 5.61% among all ADEs. Among the top 10 concomitant medications reported in ADEs, other types of antibiotics and nonsteroidal anti-inflammatory drugs were the most commonly used.

When ceftriaxone is used in children, caution should be exercised regarding its potential adverse events on the liver, gallbladder, and renal system. Additionally, attention should be paid to the risk of adverse events when used in combination with other medications.

To evaluate the influence of age on the effectiveness of midazolam oral solution in managing preoperative anxiety in pediatric patients.

Pediatric patients, aged 1 to 6 years, scheduled for elective surgery under general anesthesia, regardless of gender, American Society of Anesthesiologists Ⅰ-Ⅱ classification, were divided into two age groups: infants (1 ≤ age ≤ 3 years) and children (3 < age ≤ 6 years). The initial dose of oral midazolam solution administered was 0.5 mg·kg^-1. Subsequent dosages were determined using a bias coin design dose-up-and-down sequential method, based on the patient’s modified Ramsay sedation score, parental separation anxiety score, and facemask induction score after admission. The behavior scores and adverse reactions during sedation between the two groups were recorded and compared. The 95% effective dose (ED₉₅) and corresponding 95% confidence interval (95% CI) of midazolam oral solution for preoperative anxiety relief in children was calculated through isostatic regression analysis.

The ED₉₅ for infants and children was 0.83 mg·kg^-1 (95%CI: 0.69 to 0.88 mg·kg^-1) and 0.89 mg·kg^-1 (95%CI: 0.69 to 0.97 mg·kg^-1), respectively. No statistically significant difference in ED₉₅ was observed between the two groups (P>0.05). A comprehensive analysis of both age groups yielded an overall ED₉₅ of 0.89 mg·kg^-1 (95%CI: 0.79 to 0.97 mg·kg^-1) for midazolam oral solution in alleviating preoperative anxiety in children aged 1 to 6 years. There was a statistically significant difference in the behavior scores between the two groups (P<0.05), but no difference in parental satisfaction (P>0.05).Adverse events including hypoxemia, respiratory depression, nausea and vomiting were not observed in the two groups during the induction period and the anesthesia recovery period.

The efficacy of midazolam oral solution in alleviating preoperative anxiety in children is not affected by age. The dose of ED₉₅ for relieving preoperative anxiety in children aged 1 to 6 years is 0.89 mg·kg^-1.

To explore the median effective dose (ED₅₀) of ciprofol combined with remifentanil for sedation in painless gastroscopy of school-aged children.

School-aged children scheduled for painless gastroscopy were selected, regardless of gender, aged 6-12 years old. Following the intravenous injection of remifentanil 0.5 μg·kg^-1, the pediatric patient was administered with ciprofol (starting with an initial dose of 0.5 mg·kg^-1, the dose for the next child was determined using the Dixon sequential method, based on the sedation situation. A decrease of 0.05 mg·kg^-1 was applied for successful sedation, while an increase of 0.05 mg·kg^-1 was applied for failed sedation). The ED₅₀, 95% effective dose (ED₉₅) and corresponding 95% confidence interval (CI) of ciprofol were calculated by Probit method. The mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) of the pediatric patients before sedation (T₀), after remifentanil administration (T₁), and after ciprofol administration (T₂), as well as the occurrence of adverse reactions were recorded.

The ED₅₀ of ciprofol when combined with 0.5 μg·kg^-1 remifentanil in anesthesia induction for school-aged children in painless gastroscopy was 0.302 mg·kg^-1 (95% CI: 0.184 to 0.356 mg·kg^-1)，and the ED₉₅ was 0.461 mg·kg^-1 (95% CI: 0.390 to 1.004 mg·kg^-1). Compared with those at T₀, the MAP, HR, and RR of the children decreased significantly at T₁ and T₂ (P<0.05). Compared with those at T₁, only MAP decreased significantly at T₂ (P<0.05).During the examination, there were 6 cases of hypotension, 5 cases of bradycardia, and 5 cases of respiratory depression (including 3 cases of transient apnea), with no injection pain or chest wall rigidity.

The ED₅₀ of ciprofol combined with 0.5 μg·kg^-1 remifentanil for sedation in painless gastroscopy of school-aged children was 0.302 mg·kg^-1 (95% CI: 0.184 to 0.356 mg·kg^-1)，and the ED₉₅ was 0.461 mg·kg^-1 (95% CI: 0.390 to 1.004 mg·kg^-1).

To analyze the safety of tocilizumab in children with rheumatic immune disease and provide reference for clinical medication.

The medical records of tocilizumab from January 1st, 2016 to August 9th,2022 through the medical record system were collected. Retrospective analysis of the adverse events (AE) incidence and influencing factors, distribution, occurrence time, and outcome.

A total of 53 children treated with tocilizumab were included, 48 cases of systemic juvenile idiopathic arthritis, 1 case of Sjogren’s syndrome, 2 cases of autoimmune disease (autoimmune disease), 1 case of juvenile idiopathic arthritis (polyarticular type), and 1 case of multiple arteritis. The incidence of AE was 87% (46/53). The main AE were hypertriglyceridemia (60%), liver injury (49%), hypercholesterolemia (30%), hyperbilirubinemia (8%), neutropenia (9%), hypersensitivity (8%). Hypersensitivity was the main AE leading to drug withdrawal. The occurrence of hypercholesterolemia was associated with higher dose, and the occurrence of liver injury was associated with higher age and higher body mass index. Most of AE were mild and could recover to normal without treatment, and continuous medication rate was 96% (44/46).

The incidence of AE related to the use of tocilizumab in children is high. Hypersensitivity reactions may lead to drug withdrawal, and attention should be paid during the medication period. Although most children only suffer from mild liver injury, it is still necessary to be alert to the possibility of severe liver failure.

To evaluate the effects of remimazolam on painless gastroenteroscopy in elderly patients.

The aged patients scheduled for painless gastroenteroscopy were enrolled and randomly divided into 2 groups.The anesthesia induction regimen of the control group was sufentanil 0.1 μg·kg^-1+ propofol 1.5 mg·kg^-1, and the additional dose of propofol was 0.5 mg·kg^-1 each time during the examination. The administration regimen of the experimental group was sufentanil 0.1 μg·kg^-1 + remimazolam 0.15 mg·kg^-1 induction, and each additional dose of remimazolam was 1/3 of the first dose during the examination. Heart rate, respiratory rate, mean arterial pressure, and blood oxygen saturation during anesthesia were recorded. The time of induction, recovery and exit, and adverse reactions such as injection pain, hypoxemia and hypotension were observed.

A total of 441 patients were included in the analysis, 225 in the control group and 116 in the experimental group. Compared with the control group, the mean arterial pressure of the experimental group was higher than that of the control group at 5 and 10 min after administration, and the difference was significant (P<0.05).The induction, recovery and exit time of the experimental group were (41.8±4.3) s, (5.7±4.4) and (10.2±6.5) min, and those in the control group were (32.6±2.7) s, (6.6±3.9) and (12.9±7.4) min, respectively. The induction time of the experimental group was longer than that of the control group, and the recovery and exit time of the control group were shorter, with significant differences (P<0.05). Compared with the control group, the incidence of injection pain (54.2% vs. 2.3%), hypotension (16.4% vs. 6.9%) and hypoxemia (19.6% vs. 14.8%) in the experimental groups was significantly reduced (P<0.05).

Remimazolam is safe and effective for painless gastroenteroscopy in elderly patients, and has the advantages of fast recovery and low incidence of adverse reactions.

To investigate the effects of sub-anesthetic doses of esketamine on cerebral oxygenation and hemodynamics in elderly patients undergoing hip arthroplasty.

Sixty patients ( age ≥ 65 years and ASA classification Ⅱ to Ⅲ) for elective hip arthroplasty were selected and randomly divided into 2 groups of 30 patients each.Anesthesia was induced and maintained essentially in the same way in the two groups, with the addition of esketamine 0.5 mg·kg^-1 intravenously at the time of induction followed by continuous pumping with esketamine 0.25 mg·kg^-1·h^-1 in the experimental group, and an equal amount of sodium chloride injection given at the corresponding time point in the control group. The mean arterial pressure (MAP), heart rate (HR), surgical volume index (SPI), and regional cerebral oxygen saturation (rSO₂) were collected at the patient’s admission to the operating room (T₀), 3 min after the procedure of induction (T₁), intubation were immediately applied (T₂), 10 min after induction (T₃), skin incision (T₄) and 1 h after surgery (T₅). The intraoperative drug use and recovery quality during awakening were observed.

Compared with that at T₀, MAP (except T₄ in the experimental group) and SPI was significantly lower (P<0.05) and rSO₂ was significantly higher (P<0.05) at all time points from T₁ to T₅ in the two groups. Compared with the control group, MAP was significantly increased at T₁, T₂, T₃ in the experimental group (P<0.05). There was no significant difference in SPI, HR, and rSO₂ between the two groups from T₁ to T₅ (P>0.05). The intraoperative usage rates of atropine and ephedrine, and the dosages of propofol and remifentanil in the experimental group were significantly lower than those in the control group (P<0.05).There was no significant difference in postoperative eye opening time and extubation time between the two groups (P>0.05).

The sub-anesthetic doses of esketamine has no significant effect on the rSO₂ in elderly patients undergoing hip arthroplasty, which can provide more stable hemodynamics for patients undergoing anesthesia, and help maintain the balance between supply and demand of oxygen in brain tissue during perioperative period.

To evaluate the effects of flurbiprofen combined with quadratus lumborum block (QLB) on postoperative neurocognitive function and inflammatory response in elderly patients undergoing nephrectomy.

Sixty elderly patients undergoing laparoscopic nephrectomy were randomized into group Q (QLB group) and group FQ (flurbiprofen combined with QLB group), 30 patients in each group. Ultrasound guided anterior QLB were performed in all patients on the surgical side. Patients in group FQ received flurbiprofen 1 mg·kg^-1 iv 10 min before surgery. Then both groups received general anesthesia. The dosages of propofol and remifentanil during surgery and the effective number of analgesia pump presses were recorded. The scores of visual analogue scale (VAS) and Bruggrmann comfort scale (BCS) were evaluated at 6, 24, 48 h after surgery. The neurocognitive function was evaluated at 1 d before surgery and 1 d and 7 d after surgery using the mini-mental state examination (MMSE), and the incidence of postoperative neurocognitive disorder (PND) within 7 d after surgery was recorded. Venous blood was collected and the serum levels of high mobility group box protein 1 (HMGB1) and interleukin 6 (IL-6) were tested 1 h before surgery and 30 min and 24 h after the surgery.

Compared with group Q, the dosage of remifentanil was significantly reduced in group FQ (P<0.05), and the effective numbers of analgesia pump presses were reduced in group FQ (P<0.05). At 6, 24 h after surgery, the VAS score was lower, and the BCS score was higher in group FQ than group Q (P<0.05). Compared with group Q, the MMSE score at 1, 7 d after surgery was significantly higher in the group FQ (P<0.05), the incidence of PND within 7 d after surgery was lower in group FQ (P<0.05). The HMGB1 and IL-6 levels at 30 min, 24 h after the surgery were significantly lower in group FQ than group Q (P<0.05).

Flurbiprofen combined with QLB can reduce the incidence of PND in elderly patients undergoing nephrectomy, which may be related to the perfect early postoperative analgesia and the decreased levels of inflammatory cytokines.

To explore the effect of crocin on gastric mucosal epithelial cells injury induced by clopidogrel and the molecular mechanism.

The gastric mucosal epithelial cells GES-1 were divided into control group, model group (0.5 mmol ·L^-1 clopidogrel), and crocin low, medium, and high concentration (0.1, 1, 10 nmol·L^-1) groups, and additionally divided into anti-miR-NC group, miR-877-5p inhibitor group, crocin (10 nmol·L^-1) + miR-NC group, crocin (10 nmol·L^-1) + miR-877-5p mimic group. MTT and colony formation assays were used to detect cell survival rate and the number of colony formation. Flow cytometry was used to detect cell apoptosis. qRT-PCR was used to detect the expression level of miR-877-5p. Western blot was used to detect the expression of occludin, zonula occluden-1 (ZO-1), and p-P38 protein.

Compared with the control group, the survival rate and the number of cell clone formation in model group were decreased, the apoptosis rate and the expression of miR-877-5p and p-P38 were increased, and the expressions of occludin and ZO-1 were decreased (P<0.05). Compared with the model group, the survival rate and the number of cell clone formation in the crocin medium and high concentration groups were increased, the apoptosis rate and the expression of miR-877-5p and p-P38 were decreased, and the expression of occludin and ZO-1 were increased (P<0.05). Compared with the anti-miR-NC group, the survival rate, the number of cell clone formation, and expression of occludin and ZO-1 were increased in the miR-877-5p inhibitor group, and apoptosis rate and expression of miR-877-5p and p-P38 were decreased (P<0.05).Compared with the crocin+miR-NC group, the survival rate, the number of cell clone formation, and the expression of occludin and ZO-1 were decreased in the crocin+miR-877-5p mimic group, while the apoptosis rate and the expression of miR-877-5p and p-P38 were increased (P<0.05).

Crocin may inhibit clopidogrel-induced apoptosis of gastric epithelial cells and promote cell proliferation by down-regulating miR-877-5p.

To evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) on gastrointestinal adverse reactions in patients with type 2 diabetes mellitus (T2DM).

The databases PubMed, Embase, and Cochrane Library were systematic searched for randomized controlled trials of GLP-1RA for the treatment of T2DM from the time of construction until October 1st, 2023, with one GLP-1RA as the drug in the trial arm and placebo or another GLP-1RA as the drug in the control arm. Bayesian network meta-analysis was used to explore the risk of gastrointestinal adverse reactions, such as nausea, vomiting, anorexia, constipation, dyspepsia, and diarrhea.

Forty-five papers were included, involving 27 729 patients. The overall incidence of gastrointestinal adverse reactions caused by GLP-RA was 11.66%. Compared with placebo, tirzepatide caused the highest risk of nausea, diarrhea, dyspepsia, and anorexia, lixisenatide caused the highest risk of vomiting, and semaglutide caused the highest risk of constipation. Compared with placebo, all GLP-1RA except loxenatide significantly increased the risk of vomiting; all GLP-1RA except lixisenatide significantly increased the risk of diarrhea; all GLP-1RA significantly increased the risk of constipation except tirzepatide and lixisenatide; all GLP-1RA significantly decreased appetite and increased the risk of dyspepsia (P<0.05).

GLP-1RA significantly increased the risk of gastrointestinal adverse reactions in T2DM patients, and different drugs have different risks of various symptoms, among which tirzepatide has a higher risk of gastrointestinal symptoms, which deserves clinical attention and vigilance.

To study the mechanism of gigantol inhibiting the proliferation of pancreatic carcinoma (PC) cells by targeting urokinase-type plasminogen activator (PLAU).

PC cells (PANC-1 and SW1990) were treated with different concentrations of gigantol. The cells activity was detected by CCK-8, and half-maximal inhibitory concentration (IC₅₀) was calculated. Cell clone assay was performed to detect the effects of gigantol on cells growth ability. The effects of gigantol on cells growth cycle and apoptosis were detected by flow cytometer. The targets of gigantol were analyzed by bioinformatics, expressions of these targets in PC tissues and their relationship with poor clinical phenotypes were analyzed.PC cells were transfected with PLAU or vector plasmid, and divided into normal group (vector plasmid), gigantol group (45 μmol·L^-1 or 50 μmol·L^-1) and gigantol + PLAU (PLAU plasmid) group. The effects of gigantol on cells proliferation, clone, cells cycle and apoptosis by targeting PLAU were observed. The expression of PLAU protein in cells was detected by Western blot. The inhibitory effects of gigantol on cells proliferation in vivo were detected by xenograft assay in nude mice.The expression of proliferating cell antigen (Ki67) was detected by immunohistochemistry.

Compared with the normal group, gigantol group showed a significant decrease in cell proliferation and clone number (P<0.05), and an increase in the number of G₀/G₁-phase cells, a decrease in the number of S-phase cells (P<0.05), and an increase in the number of apoptotic cells (P<0.05). There were no significant difference in the number of G2/M-phase cells between the two groups (P<0.05). Bioinformatics results showed that PLAU was the target of gigantol, which was up-regulated in PC tissues and related to poor clinical phenotypes of PC. Gigantol could inhibit the expression of PLAU protein in PC cells, showing concentration and time dependence (P<0.05). PLAU protein expression, proliferation activity and clone number, and the number of S-phase cells in PC cells were higher in the gigantol +PLAU group than in the gigantol group, while the number of apoptotic cells was less than in the gigantol group (P<0.05). In the nude mice experiments, the volume and weight of transplanted tumors in the gigantol group were significantly lower than those in the normal group (P<0.05), and the relative expression of Ki67 in tumor tissues was lower than that in the normal group (P<0.05).

Gigantol can inhibit the proliferation of PC cells, affect cells cycle and promote apoptosis by targeting the expression of PLAU protein.

To assess the in vitro antibacterial activity of polymyxin B in combination with meropenem, amikacin, and fosfomycin against carbapenem-resistant Enterobacteriaceae (CRE) strains carrying various resistance genes.

A total of 76 CRE strains isolated from the clinical laboratory of our hospital between 2019 and 2021 were collected for identification and confirmation of carbapenemase genotype. The minimum inhibitory concentrations (MIC) of polymyxin B, meropenem, amikacin, and fosfomycin against CRE were determined using the broth microdilution method.The in vitro combined sensitivity tests of polymyxin B with meropenem, amikacin, and fosfomycin were performed using the microdilution checkerboard method to calculate the fractional inhibitory concentration index (FICI) for determining their interactions.

Among the 76 strains of CRE, 24 strains were identified to carry the bla_KPC, while 28 strains carried the bla_NDM and another 24 strains carried the bla_OXA-48-like. The drug-resistance rates of CRE strains to polymyxin B, meropenem, amikacin, and fosfomycin were determined as 3%, 92%, 39%, and 45%, respectively. The highest synergistic + partial synergistic rate was observed in combination of polymyxin B with meropenem (54%), followed by fosfomycin (43%) and amikacin (18%). For CRE carrying bla_KPC, bla_OXA-48-like, or bla_NDM, the synergistic + partial synergistic rates of polymyxin B combined with fosfomycin were 37%, 42%, and 50%, respectively, while combined with meropenem were 75%, 21%, and 64%, respectively, and combined with amikacin were 8%, 25%, and 21%, respectively. No antagonistic effect was observed between polymyxin B and these three antibiotics.

The combination of polymyxin B and meropenem exhibits the best synergistic antibacterial effect against CRE, and the combined effect is related to the drug-resistance genotype of bacteria, so active detection of drug-resistance genes can help to promote the rational use of antibiotics in clinical practice.