Latest ArticlesIschemia-reperfusion injury (I/R) is a common pathological process in clinical practice, referring to the phenomenon where the degree of tissue or organ damage intensifies when blood flow is restored after ischemia. In the urinary system, renal I/R is a key factor in inducing acute kidney injury, and its mechanism is closely related to the burst of reactive oxygen species (ROS) and systemic inflammatory responses after ischemia, which can also cause chain damage to multiple organs such as the testis through the blood circulation. Garlic, as a traditional food and medicine, its derived organic polysulfides (such as allicin, S-allyl cysteine, etc.) have been proven to have pharmacological activities such as anti-oxidative stress, anti-apoptosis and anti-inflammation. This article systematically reviews the protective effects and molecular mechanisms of garlic-derived organic polysulfides in urinary system I/R injury. At the level of oxidative stress, it restores the oxidative balance by regulating the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and ROS-generating enzymes; at the anti-apoptotic level, it inhibits excessive apoptosis of renal tubular epithelial cells by targeting the B-cell lymphoma 2 protein (Bcl-2)/ Bcl-2 associated X protein (Bax) family and cysteine aspartate-specific protease (Caspase) cascade pathways; at the anti-inflammatory level, it regulates the balance of interleukin (IL)-4/IL-10 and IL-6/ tumor necrosis factor-alpha (TNF-α), and controls the nuclear factor-kappa B (NF-κB) pathway and macrophage polarization, its protective effects have multi-target and multi-organ characteristics. This article aims to provide new ideas for the prevention and treatment of urinary system I/R-related injuries, and at the same time looks forward to further exploring the cross-regulation mechanism of oxidative stress-apoptosis-inflammation in the future, with the expectation of promoting it to become a potential clinical treatment option.
With the advancement of artificial intelligence, the European Medicines Agency released " Guiding principles on the use of large language models in regulatory science and for medicines regulatory activities" in 2024, emphasizing the importance of the safe and responsible use of large language models. This guidance covers general ethical considerations, user principles and organizational principles, clearly outlining the potential of large language models in areas such as text processing assistance and data mining, while also warning of risks such as hallucinations, data privacy issues, and biased outputs. It proposes measures including continuous learning, risk monitoring and mechanism-building to address these challenges. Although China has not yet issued similar guidelines, large language models hold potential application prospects in areas such as assisting in the processing of review materials, formulating and revising guidance principles and identifying risks. At the same time, challenges related to decision interpretability, data bias, legal accountability and talent reserves remain. It is recommended that China’s regulatory authorities draw on international experience to construct an application framework tailored to national conditions as soon as possible, thereby promoting the integration of artificial intelligence technology with the field of drug regulation.
To observe the clinical efficacy and safety of dexmedetomidine injection combined with remifentanil injection and scalp nerve block in patients undergoing craniotomy for aneurysm clipping.
Patients who underwent craniotomy for aneurysm clipping were divided into control group and treatment group according to random number method . All patients were treated with a unified scheme for anesthesia induction, and ultrasound-guided scalp nerve block was performed after induction. During the anesthesia maintenance phase, remifentanil injection (0.1-0.2 μg·kg-1·min-1), atracurium besylate injection (0.2 mg·kg-1·h-1) and propofol emulsion injection (3-8 mg·kg-1·h-1) were continuously pumped into the two groups. And dexmedetomidine injection (0.4 μg·kg-1·min-1) was pumped into the treatment group on the basis of control group. The recovery time, extubation time, hemodynamic changes, analgesia and sedation scores, brain injury and emergency response related markers were compared between the two groups, and the safety was evaluated.
A total of 110 cases were enrolled, including 55 in control group and 55 in treatment group. The recovery time of control group and treatment group were (19.73±3.52) and (17.87±2.69) min, respectively; and the extubation time were (21.78±3.83) and (19.33±3.46) min, respectively; the mean arterial pressure (MAP) at 5 minutes after intubation (T1) were (83.67±12.99) and (89.31±14.39) mmHg, respectively; and at nerve block (T2), the MAP were (81.40±13.92) and (86.58±12.18) mmHg, respectively; at 10 minutes after the operation (T5), the MAP were (83.56±12.58) and (89.02±13.48) mmHg, respectively; and the heart rate (HR) at T1 were (65.55±11.39) and (72.42±11.66) beats·min-1, respectively; the HR at T2 were (63.65±13.54) and (70.15±12.29) beats·min-1, respectively; at 10 minutes after nerve block (T3), the HR were (64.65±14.26) and (71.13±12.49) beats·min-1, respectively; when sawing the skull (T4), the HR were (62.44±12.67) and (69.02±13.57) beats·min-1, respectively; and at T5, the HR were (67.18±10.40) and (74.84±13.77) beats·min-1, respectively. Compared with control group, the differences of the above indicators of treatment group were all statistically significant (all P<0.05). The total incidence of adverse drug reaction rates in control group and treatment group were 30.91% (17 cases /55 cases) and 14.55% (8 cases /55 cases), respectively, with statistically significant difference (P<0.05).
Dexmedetomidine injection combined with remifentanil injection and scalp nerve block has good clinical efficacy and safety in craniotomy and aneurysm clipping.
To observe the clinical efficacy and safety of subanesthetic dose of esketamine injection and quadratus lumborum block in elderly patients undergoing radical resection of colorectal cancer.
Patients undergoing radical resection of colorectal cancer were divided into treatment group and control group according to the anesthesia method. Both groups underwent bilateral quadratus lumborum block under ultrasound guidance. Anesthesia induction was performed with etomidate injection at a dose of 0.1-0.3 mg·kg-1, sufentanil injection at a dose of 0.3-0.6 μg·kg-1, midazolam injection at a dose of 0.04-0.06 mg·kg-1, and cisatracurium injection at a dose of 0.2 mg·kg-1. Anesthesia was maintained with propofol injectation emulasion 4-8 mg·kg-1·h-1, remifentanil for injection 0.15-0.3 μg·kg-1·min-1, and dexmedetomidine injection 0.2-1.0 μg·kg-1·h-1. The treatment group received a single intravenous injection of 0.25 mg·kg-1 esketamine injection 5 min before surgery, while the control group received routine anesthesia management without esketamine injection intervention. Both groups received intravenous patient-controlled analgesia postoperatively. Hemodynamics, analgesia and sedation, postoperative opioid consumption, and recovery quality were compared between the two groups, and safety was evaluated.
A total of 108 patients were enrolled, the treatment group included 52 cases and the control group included 56 cases. The mean arterial pressure (MAP) at T3 in the treatment and control groups were (86.04±6.43) and (83.20±6.80) mmHg, respectively; the heart rate (HR) at T3 were (76.21±5.56) and (73.96±5.31) beats·min-1, respectively; the numerical rating scale (NRS) at 12 h postoperatively were (2.04±0.77) and (2.29±0.65) points, respectively; sufentanil consumption were (88.63±11.28) and (94.30±12.22) μg, respectively; the effective pressing times of the analgesia pump within 24 h postoperatively were (5.65±1.17) and (6.23±1.40) times, respectively, and the effective pressing times of the analgesia pump within 24-48 h postoperatively were (7.06±1.51) and (7.89±2.18) times, respectively; the awakening time were (21.25±4.58) and (23.68±4.87) min, respectively, and the length of stay in the postanesthesia care unit (PACU) were (36.23±6.91) and (40.05±7.42) min, respectively. The differences were all statistically significant (P<0.05, P<0.01). The adverse drug reactions in the treatment group were dizziness, nausea and vomiting, while the adverse drug reaction in the control group was skin pruritus. The total incidence of adverse reactions in the treatment and control groups was 3.85% (2 cases/52 cases) and 1.79% (1 case/56 cases), respectively, and the difference was not statistically significant (P>0.05).
The application of subanesthetic dose of esketamine and quadratus lumborum block in elderly patients undergoing radical resection of colorectal cancer can effectively reduce postoperative opioid consumption, provide good sedation and analgesia, maintain hemodynamic stability, protect lung function, and improve recovery quality. It has little impact on cognitive function and sleep quality, and has good safety.
To observe the clinical efficacy and safety of duloxetine hydrochloride enteric-coated capsules combined with Bifidobacterium quadruple live bacteria tablets in patients with depression accompanied by gastrointestinal disorders.
According to the treatment method, patients with depression and gastrointestinal dysfunction were divided into control group and treatment group. The control group took 30 mg duloxetine hydrochloride enteric-coated capsules once a day after breakfast, and adjusted to 60 mg once a day after 1 week. The treatment group was combined with 1.5 g Bifidobacterium quadruple viable tablets, 3 times a day. Both groups were treated for 8 weeks. The clinical therapeutic effects, and intestinal microbiota composition of the two groups of patients were compared, and safety evaluation was conducted.
A total of 76 patients were enrolled, 32 patients were included in the control group and 44 patients in the treatment group. After treatment, the total effective rate of the treatment group was 84.09% (37 cases /44 cases), and that of control group was 62.50% (20 cases/32 cases), and the difference was statistically significant (P<0.05). After treatment, the Lactobacillus of treatment group and control group were (7.14±1.14) and (6.54±1.24) lg CFU·g-1, respectively; Staphylococcus were (3.73±0.73) and (4.12±0.74) lg CFU·g-1, respectively; Bifidobacterium were (8.39±1.44) and (7.69±1.34) lg CFU·g-1, respectively; Escherichia coli were (7.08±0.93) and (7.52±0.81) lg CFU·g-1, respectively; Enterococcus faecalis were (5.95±0.76) and (6.50±0.84) lg CFU·g-1, respectively. The above indicators of treatment group were compared with those of the control group, and the differences were statistically significant (all P<0.05). The adverse drug reactions in the treatment group mainly included nausea, dry mouth, constipation, insomnia and dizziness. The adverse drug reactions in the control group mainly included palpitations, nausea, dry mouth, constipation, insomnia and dizziness. The total incidence of adverse drug reactions in the treatment group and the control group were 15.91% (7 cases /44 cases) and 40.63% (13 cases /32 cases), respectively, with no statistically significant different (P<0.05).
Duloxetine hydrochloride enteric-coated capsules combined with Bifidobacterium quadruflora live bacteria tablets have a good clinical efficacy in patients with depression accompanied by gastrointestinal disorders. They can improve the intestinal flora of patients and reduce the occurrence of adverse drug reactions.
To observe the clinical efficacy and safety of emedastine difumarate sustained-release capsules in conjunction with tacrolimus ointment for treating elderly patients with skin pruritus.
The senile patients with pruritus who were treated in our hospital were divided into control group and treatment group according to the treatment methods. The control group was treated with tacrolimus ointment twice a day on the basis of conventional treatment for 6 consecutive weeks. The treatment group, on the basis of the control group, orally administered 2 mg of emestine fumarate sustained-release capsules after breakfast or before going to bed, twice a day for 6 consecutive weeks. The clinical efficacy of patients, evaluation of itching degree, the levels of eosinophils (EOS), histamine and immunoglobulin E (IgE), levels of inflammatory response indicators recurrence situation, and safety were compared between two groups.
A total of 122 cases were included in this study, including 59 cases in the control group and 63 cases in the treatmnet group. The total effective rates of treatment in the treatmnet group and the control group were 92.06% (58 cases/63 cases) and 76.27% (45 cases/59 cases), respectively; the pruritus degree scores were (2.35±0.48) and (2.64±0.52) points, respectively; the EOS were (208.07±33.69) and (225.61±34.82) ×106·L-1 respectively; the histamine was (0.79±0.13) and (1.25±0.21) ng·mL-1, respectively; the IgE was (42.07±6.56) and (45.17±6.08) ng·mL-1, respectively; the monocyte chemoattractant protein-1 was (279.77±39.14) and (298.52±47.64) pg·mL-1, respectively; the eosinophil chemoattractant was (44.77±6.21) and (47.96±7.45) pg·mL-1, respectively; the interleukin-6 was (6.56±1.07) and (7.13±1.08) pg·mL-1, respectively; the tumor necrosis factor -α was (5.91±0.69) and (6.24±0.89) pg·mL-1, respectively, and the recurrence rates were 11.11% and 25.42%, respectively. The comparison of above indicators showed that there were statistically significant differences between the two groups (P<0.05, P<0.01, P<0.001). The adverse reactions in the control group included a burning sensation on the skin and rosacea, while those in the treatmnet group included a burning sensation on the skin, rosacea, drowsiness, headache, dizziness and tinnitus. The adverse reaction rates of the control group and the treatmnet group were 11.86% and 19.05%, without tatistically significant difference (P>0.05).
Emedastine difumarate sustained-release capsules combined with tacrolimus ointment can alleviate patients′ pruritus symptoms, reduce inflammatory response, regulate immune function, improve efficacy and reduce the risk of recurrence without increasing adverse reactions.
To understand the distribution and antibiotic resistance changes of clinical isolated Klebsiella pneumoniae in Xinjiang from 2019 to 2023, and provide a basis for the rational use of antibiotics in clinical practice.
Clinical isolates from Xinjiang region between 2019 and 2023 were collectd and identified and subjected to drug sensitivity tests using the fully automated bacterial identification analyzer VITEK-2 compact and VITEK-MS, supplemented by the K-B paper method.
Over the course of 5 years, a total of 72 678 strains of Klebsiella pneumoniae were detected, among which 19 061 were extended-spectrum β-lactamases (ESBLs) producing strains, accounting for a detection rate of 26.23%. The strains mainly come from sputum, urine, blood, etc. The top three departments in terms of strain distribution were the intensive care medicine, respiratory medicine, and pediatrics. The resistance rates of Klebsiella pneumoniae to third-generation cephalosporins ceftriaxone and ceftazidime were 21.42% and 15.73%, respectively. The resistance rates to carbapenems ranged from 6.82% to 7.48%, and the resistance rate to amikacin was 4.15%.
Klebsiella pneumoniae has become one of the most common pathogenic bacteria in clinical practice. The resistance of Klebsiella pneumoniae detected in Xinjiang is not optimistic. In order to improve the treatment effect of antibiotics, the resistance of antibiotics in the local area should be continuously monitored, and antibiotics should be selected reasonably based on drug sensitivity results.
To evaluate the in vitro antibacterial effects and post-antibiotic effect (PAE) of dequalinium chloride against common pathogens isolated from oral infections in China in recent years.
The minimum inhibitory concentration (MIC) was determined by the standard microbroth or agar (for anaerobes) two-fold dilution method; the minimum bactericidal concentration (MBC) was determined by the broth two-fold dilution method; time-kill curves and PAE were determined by the colony count method.
MICs of dequalinium chloride and commonly used antimicrobial drugs were determined for 274 bacterial strains from 22 hospitals in 19 cities across China. Result showed that, for Gram-positive bacteria, the MIC50 values of dequalinium chloride against Staphylococcus aureus and Streptococcus pyogenes were 1 and 2 mg·L-1, respectively, with MIC90 values of 2 and 4 mg·L-1, respectively. For Streptococcus pneumoniae, Enterococcus faecalis, and the viridans group streptococci, the MIC50 values were 8, 4 and 8 mg·L-1, respectively, while the MIC90 values were 8, and 16 mg·L-1, respectively. Among Gram-negative bacteria, the MIC50 and MIC90 values of dequalinium chloride against Klebsiella pneumoniae were both 64 mg·L-1; and >512 mg·L-1 for MIC50 against Pseudomonas aeruginosa. For 32 strains of anaerobic bacteria, the MIC50 and MIC90 of dequalinium chloride were 16 and 128 mg·L-1, respectively. Dequalinium chloride showed superior antibacterial activity against genera of Peptostreptococcus and Porphyromonas compared to Prevotella. MBC and time-kill curves showed that dequalinium chloride has a good bactericidal effect on Staphylococcus aureus, Streptococcus pyogenes, and oral streptococci, killing bacteria from an initial count of 1.0×105-1.0×106 CFU·mL-1 to 0 at 1-4 times MIC concentration within 4-24 h. It also showed good bactericidal effect on Enterococcus faecalis. The time-kill curves indicating a concentration-dependent characteristic of the drug. The PAE of dequalinium chloride against the above four bacterial strains was between 0.5-1 h.
Dequalinium chloride exhibits superior antibacterial activity against Gram-positive bacteria than Gram-negative bacteria and anaerobes, especially against Staphylococcus aureus and Streptococcus pyogenes, warranting further clinical research.
To evaluate in vitro activity of ceftobiprole against clinical isolated bacteria in recent years in China.
The minimal inhibitory concentrations (MICs) were determined by the microbroth dilution method.
A total of 948 clinical isolates collected from nationwide between 2019 to 2020 were studied. Ceftobiprole exhibited excellent antibacterial activity against gram-positive cocci, the value of MIC90 was 0.5 mg·L-1 for methicillin susceptible Staphylococcus spp and susceptibility rates of methicillin resistant Staphylococcus aureus (MRSA) were 93.1%, which was better than that of ceftaroline (72.3%). The MIC values of ceftobiprole against penicillin nonsusceptible Streptococcus pneumoniae (PNSSP) ranged from 0.06 to 1 mg·L-1, with 80.0% susceptibility rate . The values of MIC90 of ceftobiprole were ≤2 mg·L-1 for other streptococci and Enterococcus faecalis. Against Gram-negative bacteria, ceftobiprole also showed better antibacterial activity against non-extended spectrum β-lactamases (ESBLs) Escherichia coli, non-ESBLs Klebsiella pneumoniae, ampicillin-susceptible Haemophilus influenzae and Moraxella catarrhalis, the values of MIC90 ≤0.5 mg·L-1 and susceptible strains more than 98.1%. The activity of ceftobiprole against Pseudomonas aeruginosa was similar to that of ceftazidime and cefepime.
Ceftobiprole showed excellent antibacterial activity against clinical isolates, include MRSA, PNSSP, and Haemophilus influenzae in recent years in China, which similar to the surveillance results in Europe and America. The clinical prospect is worthy of expectation.
To discuss the effects of acacetin on lung injury in Mycoplasma pneumoniae pneumonia (MPP) mice and analyze the relationship between its mechanism and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
A MPP mouse model was constructed, and successfully modeled mice were stochastically divided into model group, low, medium and high dose acacetin experimental groups (acacetin-L, M, and H groups: 12.5, 25.0, and 50.0 mg·kg-1 acacetin) and high-dose acacetin-H+JAK2 activator coumarin group (acacetin-H+coumarin 50 mg·kg-1 acacetin-L and 2 mg·kg-1 coumarin), each with 12 mice. Twelve normal healthy mice were intranasally instilled with an equal amount of physiological saline as the control group. Blood gas analyzer was used to detect arterial partial pressure of carbon dioxide (PaCO2) and arterial partial pressure of oxygen (PaO2) of mice, oxygen concentration analyzer was used to detect fraction of inspired oxygen (FiO2), and the oxygenation index (OI) was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory factors. Biochemical method was used to detect oxidative stress indicators. The lung index and lung wet dry ratio were weighed and calculated. Hematoxylin-eosin (HE) staining was employed to evaluate the pathological lesions in lung tissue. Western blot assay was performed to detect the protein expression of JAK2/STAT3 signaling pathway-related molecules.
The OI value of the acacetin-L, -M, -H groups, control group, model group, and acacetin-H+coumamycin group were (274.63±30.02), (320.16±35.79), (374.55±39.88), (403.57±43.61), (220.31±26.78) and (241.03±29.14)mmHg, respectively; the IL-6 levels were (124.56±13.27), (87.61±9.23), (56.34±6.77), (36.50±4.15), (172.59±18.24) and (149.33±16.05)pg·mL-1, respectively; the MDA contents were (4.06±0.45), (2.97±0.31), (1.93±0.22), (1.82±0.20), (5.31±0.58) and (4.69±0.49) nmol·mL-1, respectively; the lung index was 1.31±0.15, 0.99±0.11, 0.57±0.07, 0.52±0.06, 1.78±0.19, and 1.54±0.17, respectively; the lung wet/dry weight ratio was (6.83±0.73)%, (5.61±0.58)%, (4.35±0.49)%, (4.10±0.45)%, (7.86±0.86)% and (7.33±0.81)%, respectively; the phosphorylated(p)-JAK2/JAK2 ratio were 0.71±0.08, 0.56±0.06, 0.43±0.05, 0.39±0.04, 0.86±0.09 and 0.79±0.08, respectively; the p-STAT3/STAT3 ratio were 0.67±0.07, 0.46±0.06, 0.30±0.04, 0.16±0.02, 0.83±0.09 and 0.74±0.08, respectively. There were statistically significant differences in the above indicators between the model group and the control group, between the acacetin-H group and the model group, and between the acacetin-H+coumarin group and the acacetin-H group (all P<0.05).
Acacetin can effectively improve lung injury in MPP mice, possibly by inhibiting the JAK2/STAT3 signaling pathway.