Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

Objective:To explore the clinical efficacy and safety of endoscopic multi-band ligation (EMBL) in the management of refractory gastroesophageal reflux disease (RGERD) combined with esophageal hiatal hernia (HH).Methods:This study was a prospective, multicenter, small-sample cohort study. Patients who were diagnosed as having RGERD combined with HH at Inner Mongolia Medical University Cancer Hospital and Inner Mongolia Medical University Hospital from January 2020 to June 2022 were selected to undergo EMBL. The 24-hour esophageal pH monitoring and high-resolution manometry (HRM) related indicators, gastroesophageal reflux index (GERI), gastroesophageal reflux disease questionnaire (GERD-Q) scores, and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores were compared before and after the operation. The patient satisfaction and complications were also investigated.Results:A total of 25 patients were included, all of whom were successfully treated with EMBL. Reflux symptoms were relieved to varied degrees in all patients. There were no serious complications during or after the operation, such as perforation, bleeding, and dysphagia. Postoperative follow-up at 6 and 12 months showed a significant decrease in DeMeester scores [18.00 (5.83, 54.75) points, 16.30 (4.38, 60.00) points] compared to preoperative baseline [105.00 (60.80, 147.70) points, Z=-3.72, P<0.001; Z=-3.82, P<0.001]. The percentage of time of pH<4 [8.80 (6.10, 11.80)%, 8.95 (5.15, 10.90)%] significantly decreased compared to the baseline [31.15 (16.75, 54.75)%, Z=-3.72, P<0.001; Z=-3.72, P<0.001], the number of long refluxes [7.90 (4.93, 11.75) times, 6.90 (4.00, 10.75) times] significantly decreased compared to the baseline [33.00 (13.00, 43.00) times, Z=-3.82, P<0.001; Z=-3.58, P<0.001], and the number of acid refluxes (14.86±8.71 times, 12.93±5.51 times) significantly decreased compared to before (30.42±17.99 times, t=5.88, P<0.001; t=4.79, P<0.001). Lower esophageal sphincter resting pressure [9.70 (5.80, 19.58) mmHg, 11.70 (5.40, 19.78) mmHg] was significantly higher compared to before [4.70 (3.25, 7.00) mmHg, Z=-2.84, P<0.001; Z=-3.10, P<0.001]. GERD-Q scores (10.00±2.01 points, 9.43±1.74 points) were significantly higher compared to before (15.34±1.51 points, t=8.90, P<0.001; t=9.87, P<0.001), GERD-HRQL scores [7.00 (5.00, 7.75) points, 6.00 (5.75, 8.25) points] significantly decreased compared to preoperative baseline [13.50 (11.00, 21.25), Z=-3.73, P<0.001; Z=-3.72, P<0.001], and GERI (2.26%±1.58%, 2.07%±1.17%) significantly decreased compared to before (5.72%±2.27%, t=8.92, P<0.001; t=9.86, P<0.001). At 6 and 12 months postoperative follow-up, patient satisfaction [68.00% (15/25), 84.00% (21/25)] significantly increased compared to before [0.00% (0/25), Z=-4.63, P<0.001; Z=-6.48, P<0.001]. Conclusion:Preliminary small-sample study has shown that EMBL is safe, reliable and effective for the treatment of RGERD with HH.

OBJECTIVE To analyze the relationship between the postoperative intervertebral space infection and the expressions of β-catenin and glycogen synthase kinase-3β(GSK-3β)in the patients with lumbar disc herniation(LDH).METHODS A total of 201 patients with LDH who received surgical procedures in Harbin Orthopedics and Traumatology Hospital from Jan.2022 to May 2024 were enrolled in the study and were divided into the infection group and the no infection group according to the status of postoperative intervertebral space infection.The distri-bution and drug resistance of pathogens isolated from the patients of the infection group were detected.The rela-tive expression levels of peripheral blood Wnt,β-catenin and GSK-3β proteins were compared between the two groups.RESULTS Among the 201 patients who received surgical procedures,21 had postoperative intervertebral space infections,with the infection rate 10.45％.Totally 26 strains of pathogens were isolated from the 21 patients in the infection group,11(42.31％)of which were gram-negative bacteria,and 15(57.69％)were gram-positive bacteria.The operation duration of the infection group was(3.46±0.89)hour,longer than(3.09±0.73)hour of the no infection group(t=2.146,P=0.033).There were significant differences in the expressions of peripheral blood β-catenin and GSK-3β proteins between the infection group and the no infection group(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the areas under the curves(AUCs)of the relative ex-pression levels of β-catenin and GSK-3β were 0.836 and 0.800,respectively;the sensitivities were 52.40％and 66.70％,respectively;the specificities were 90.56％and 93.89％,respectively;the cut-off point were 5.65 and 2.15,respectively.CONCLUSIONS The LDH patients are at high risk of postoperative intervertebral space infec-tion,the patients with the infection show the activation of Wnt/β-catenin signaling pathways and the rise of ex-pression levels of β-catenin and GSK-3β proteins.The levels of the indexes may facilitate the prediction of postop-erative intervertebral space infection in the LDH patients.

Objective To clarify the evidence of the frequency and risk factors for falls in knee osteoarthritis(KOA)of adults by meta-analysis.Methods Computerized searches of the CNKI,VIP,Wanfang data,CBM,PubMed,Cochrane Library,Embase,Web of Science were conducted for literature on risk factors for falls in adults with KOA from the inception of the databases to August 2024.After literature screening,data extraction,and quality evaluation,RevMan 5.4 software was used for Meta-analysis.Results A total of 26 articles were involved.Meta-analysis result showed that the rate of falls was 29.0％.Factors associated with increased risk of falls included being female(OR=1.35),decreased lower limb muscle strength(OR=1.72),decreased knee flexion muscle strength(OR=7.05),decreased static posture stability(OR=1.28),opioid use(OR=1.79),antidepressant use(OR=1.69),frequent stair climbing(OR=7.58),combined neurological disease(OR=1.77),history of falls(OR=3.29)and fear of falling(OR=2.54).Conclusion The rate of falls of patients with KOA is high.The adults with KOA who are women,have lower muscle strength of lower limbs and knee flexion muscle strength,poorer static posture stability,use opioids,antidepressant,frequent stair climbing,combined neurological disorders,previous falls in the past year and fear of falls are at higher risk of falls.Healthcare professionals should dynamically assess and detect the risk of falls in the patients with KOA and adopt targeted,individualized interventions to prevent falls.

Objective To investigate pharmacologically active components of Yiqi Zishen Formula(YZF)and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease(COPD).Methods Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum.A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis.A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways.Fifty male C57BL/6J mice were randomized equally into control group,COPD model group,high-and low-dose YZF treatment groups,and N-acetylcysteine treatment group.Pulmonary function of the mice was assessed using whole-body plethysmography,and lung histopathology,alveolar structure,and airway remodeling were analyzed using HE staining.The levels of IL-1β,IL-6,and TNF-α in bronchoalveolar lavage fluid(BALF)were determined with ELISA,and pulmonary expressions of PI3K,Akt,phosphorylated Akt(p-Akt),p65,and phosphorylated p65(p-p65)were detected using immunohistochemistry.Results We identified a total of 156 chemical components(including 26 flavonoids or flavonoid glycosides,27 alkaloids,and 11 saponins)in YZF and 43 prototype components in medicated rat serum.Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets.Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway.In mouse models of COPD,YZF treatment significantly increased mean alveolar number and peak expiratory flow(P<0.05),reduced mean linear intercept,bronchial wall thickness,lung coefficient,and BALF cytokine levels,and suppressed the expressions of PI3K,Akt,p-Akt,p65,and p-p65 in the lung tissues.Conclusion YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF-κB pathway through its multiple components that interact with multiple targets.

Objective With the development of manned space missions to the moon and space exploration,extravehicular activities become more frequent and extravehicular mission become more complex,which puts forward higher requirements for the extravehicular spacesuit.In order to ensure the ergonomics of spacesuit,the flexible joints are usually adopted in the limbs of spacesuit.The structural design of large angle of movement and low resistance joints is the basic for ensuring the ergonomics of spacesuit.Methods This study established a method of spacesuit joint structure to analysis the motion characteristic of typical joints.Firstly,the structure and activity characteristics of the spacesuit and lunar space suits were comprehensively analyzed,and the activity characteristics of different typical structure are qualitatively analyzed based on existing empirical method.Then,the dynamics of typical structure was analyzed by finite element model.By studying the change trend of motion of spacesuit joint with motion angle,and the motion characteristic curve was obtained.Finally,the model was studied according to different structural size parameters.The influence of structural parameters on the motion characteristics was analyzed,and the curves was obtained to provide a basis for design of spacesuit motion joint structure.Results Through the above analysis,the motion characteristics of different typical structure are obtained qualitatively.And the influence of different structure parameters on the motion characteristics was analyzed.This establishes the method basis for structure design.Conclusion The study was carried out a method based on finite element model for joint motion analysis,which is suitable for the design of typical joint structure of spacesuit.

Objective To discuss the application value of comfort medical mode in patients with uterine fibroids receiving interventional embolization therapy during hospitalization.Methods A total of 27 patients with uterine fibroids,who received interventional embolization at the Third Affiliated Hospital of Zhengzhou University of China,were enrolled in this study.The patient's basic data,including age,the sum of the maximum diameter of the measurable uterine fibroids and the hemoglobin level at admission,were collected.After admission and before discharge,the self-efficacy scale score,Becker anxiety scale score,and positive and negative emotions scale score were determined in all the patients.According to the different medical management mode adopted during the hospitalization,the patients were divided into study group(n=14)and control group(n=13).Comfort medical mode guided by quantitative evaluation strategy was employed for the patients of the study group,while conventional management mode was adopted for the patients of the control group.SPSS 26.0 software was used for data analysis.Measurement data within group were analyzed by independent sample t-test,and measurement data between groups were analyzed by paired sample t-test,and P＜0.05 was defined as a statistically significant difference.Results There were no statistically significant differences in the basic data between the two groups,and no statistically significant differences in the self-efficacy scale score,Becker anxiety scale score,and positive and negative emotions scale score at admission existed between the two groups.In the study group,the self-efficacy score and positive emotion score at discharge were strikingly higher than those at admission(P＜0.001),and the anxiety degree and negative emotion score at discharge were obviously lower than those at admission(P＜0.001).In the control group,the scores of the above-mentioned scales at discharge did not differ from those at admission.Conclusion The comfort medical mode guided by quantitative evaluation strategy has better clinical effect in patients with uterine fibroids receiving interventional embolization therapy,it can improve patient's comfortableness degree during hospitalization period.

OBJECTIVES: To investigate pharmacologically active components of Yiqi Zishen Formula (YZF) and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease (COPD). METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum. A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis. A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways. Fifty male C57BL/6J mice were randomized equally into control group, COPD model group, high- and low-dose YZF treatment groups, and N-acetylcysteine treatment group. Pulmonary function of the mice was assessed using whole-body plethysmography, and lung histopathology, alveolar structure, and airway remodeling were analyzed using HE staining. The levels of IL-1β, IL-6, and TNF‑α in bronchoalveolar lavage fluid (BALF) were determined with ELISA, and pulmonary expressions of PI3K, Akt, phosphorylated Akt (p-Akt), p65, and phosphorylated p65 (p-p65) were detected using immunohistochemistry. RESULTS: We identified a total of 156 chemical components (including 26 flavonoids or flavonoid glycosides, 27 alkaloids, and 11 saponins) in YZF and 43 prototype components in medicated rat serum. Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets. Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway. In mouse models of COPD, YZF treatment significantly increased mean alveolar number and peak expiratory flow (P<0.05), reduced mean linear intercept, bronchial wall thickness, lung coefficient, and BALF cytokine levels, and suppressed the expressions of PI3K, Akt, p-Akt, p65, and p-p65 in the lung tissues. CONCLUSIONS YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF‑κB pathway through its multiple components that interact with multiple targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Male ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; NF-kappa B/metabolism* ; Inflammation/drug therapy* ; Rats

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents