OBJECTIVE To evaluate the effect of manipulation of Imipenem and cisplatin sodium （ICS） for injection on the consistency of its main drug imipenem （IPN） content， and the stability of different concentrations of ICS solution， to provide a reference for the safe and effective use of ICS in children. METHODS Three operators prepared ICS solutions according to the two commonly used dosage methods for children （10 mL or 20 mL 0.9% Sodium chloride injection to prepare the initial ICS solution and draw the required dose from the initial suspension）. The content of IPN was determined by ultra-high performance liquid chromatography-tandem mass spectrometry after parallel processing. The content consistency of solutions in each group was determined according to the coefficient of variation （CV）＜15% of the IPN content. ICS test solution X1 was prepared according to the instructions， and then test solutions X2 and X3 were prepared by diluting X1 with 0.9% Sodium chloride injection in the volume ratios of 1∶1 and 1∶2， which were stored at room temperature （[ 23.0±0.5） ℃]， in a thermostatic water bath at 30 ℃， and in a refrigerator at 2-8 ℃. The stability of the drug solution was determined by the ratio of the IPN mass concentration measured at the specified temperature and time to the initial （0 h） mass concentration （if the ratio was≥90%， it was considered that the drug solution was stable）. RESULTS CV of IPN content was ＜15% in each group of solutions prepared with two manipulation methods by each operator， indicating a small deviation in IPN content. The solutions at the three concentration levels were stable at room temperature for 6 h or refrigerated for 18 h. The test solutions X1 and X2 were also stable when placed at 30 ℃ for 6 h， but the IPN concentration in test solution X3 decreased by about 20% compared with that of 0 h. CONCLUSIONS The consistency of the content of IPN is good in the two commonly used methods for ICS manipulation in children. The stability of ICS solution is affected by concentration， temperature and time. Lower concentrations at higher temperatures resulted in decreased stability of IPN. Clinical attention should be paid to controlling the amount of solvent as well as temperature and time during preparation and use.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Mechanical ventilation is commonly employed for respiratory support in patients with respiratory failure. Despite the optimization of ventilator parameters and treatment methods, mechanical ventilation can still lead to both acute and chronic lung injury in patients with acute respiratory distress syndrome (ARDS) as well as in those without ARDS, a phenomenon referred to as ventilator-induced lung injury (VILI). VILI can be categorized into four types: barotrauma, volumetric injury, atelectasis injury, and biotic injury. Among these, biotic injury, characterized by inflammation, plays a significant role in the pathogenesis of VILI. Numerous studies have investigated the inflammatory mechanisms underlying VILI; however, these mechanisms remain complex and not entirely understood. At present, clinical practice lacks specific prevention and treatment strategies for VILI, aside from the implementation of protective ventilation strategies. Long non-coding RNAs (lncRNA) are a category of non-coding RNA longer than 200 nucleotides. LncRNAs regulate physiological and pathological processes such as cell proliferation, apoptosis, inflammatory response, and immune regulation, this regulation occurs through mechanisms such as modulating gene activity, inhibiting specific states, assisting in transcription initiation, affecting pre-mRNA splicing modifications, influencing translation processes, and expressing biofunctional peptides. They play an important role in the course of multiple diseases. Studies have shown that compared with control animals and cell models, lncRNAs are differentially expressed in VILI animal models and cell stretch models. Experiments have verified that certain lncRNAs play a crucial role in the pathogenesis of VILI by regulating the expression of inflammatory factors, the transformation of macrophage types, neutrophil activation, and cell apoptosis. Given the adverse effects of VILI on mechanical ventilation in critically ill patients, the important role of lncRNAs in biological regulation, and the urgent need to explore more effective strategies for the prevention and treatment of VILI, this paper summarizes the mechanisms through which lncRNA contributes to the VILI process, and discusses its possibility as a diagnostic and therapeutic target of VILI, in order to provide a reference for the clinical treatment of VILI.
RNA, Long Noncoding ; Ventilator-Induced Lung Injury ; Humans ; Respiration, Artificial/adverse effects* ; Animals ; Respiratory Distress Syndrome ; Apoptosis

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe critical condition marked by rapid progression and high fatality. It results from direct/indirect lung-related or systemic triggers, leading to widespread injury of lung epithelial and endothelial cells. Its pathogenesis involves uncontrolled inflammation and breakdown of the lung's blood-air barrier due to leaky blood vessels and epithelial damage. Current management of ALI/ARDS remains primarily supportive, offering symptomatic relief but limited improvement in prognosis, necessitating deeper exploration of upstream pathogenic mechanisms to identify safer and more effective therapies. Exosomal microRNAs (miRNA), small extracellular vesicles (40-150 nm) containing non-coding single-stranded RNAs, regulate post-transcriptional cellular processes and participate in ALI/ARDS pathophysiology. Studies reveal that exosomes transport proteins, nucleic acids, and miRNAs to recipient cells, mediating intercellular communication. In ALI/ARDS models, exosomal miRNAs delivered to alveolar epithelial cells, endothelial cells, macrophages, and neutrophils critically modulate autophagy, pyroptosis, apoptosis, proliferation, inflammatory signaling, macrophage polarization, and neutrophil activation, either exacerbating or alleviating disease progression. Recent advances in engineering techniques have enhanced the therapeutic potential of exosomal miRNAs by overcoming limitations of natural exosomes. This review focuses on exosomal miRNA-mediated regulation of ALI/ARDS pathogenesis across key cell types, providing insights for novel therapeutic strategies.
Exosomes ; Humans ; MicroRNAs ; Acute Lung Injury ; Respiratory Distress Syndrome ; Animals

Objective: To evaluate the clinical efficacy of a novel autologous blood recovery device during the weaning process from extracorporeal membrane oxygenation (ECMO). Methods: A total of 16 patients who received ECMO support and underwent blood recovery during the weaning process from January 2022 to September 2024 at our hospital were included in the experimental group. In contrast, 58 patients who did not receive blood recovery during the weaning process were assigned to the control group. Transfusion components, costs, and changes in routine blood tests and coagulation functions were compared between the two groups from the day of weaning until 48 hours post-weaning. Results: Significant differences were observed in the volumes of red blood cell transfusions, plasma transfusions, and transfusion costs between the two groups from the day of weaning to 48 hours post-weaning (P<0.05). Additionally, in the experimental group, significant differences were noted in hemoglobin (Hb), platelet (Plt), and activated partial thromboplastin time (APTT) results when comparing values before and after extubation (P<0.05). Conclusion: The application of a novel autologous blood recovery device during ECMO weaning reduces patient costs, minimizes wastage of autologous blood, decreases reliance on exogenous blood transfusions, and mitigates the risks associated with allogeneic blood transfusion. This approach merits further promotion for clinical use.

Background Suicidal ideation serves as a sensitive predictive indicator for non-suicidal self-injury(NSSI)behavior,and NSSI behavior brings profound effects to both mental and physical health of senior high school students.Existing studies have made exploration on the relationship among insomnia,anxiety and NSSI behavior in the general population,but the internal mechanism of NSSI behavior in senior high school students with suicidal ideation requires further study.Objective To explore the pathway of anxiety between insomnia and NSSI behavior in senior high school students,so as to provide references for the intervention on NSSI behavior in such demographic.Methods From December 10 to 15,2021,cluster sampling was adopted to select 2 572 senior high school students across three senior high schools in Hubei Province as the research objects.Assessment was conducted by using Insomnia Severity Index(ISI),Generalized Anxiety Disorder Scale-7 item(GAD-7)and Adolescents Self-Harm Scale.Spearman correlation analysis was conducted to examine the correlation among scores of scales finished by senior high school students with suicidal ideation.Model 4 from the SPSS 20.0 Process 4.2 was employed to test the mediating path of anxiety between insomnia and NSSI behavior.Results A total of 2 421 valid questionnaires(94.13%)were recovered,which revealed 554 cases(22.88%)with suicidal ideation and 408 cases(16.85%)with NSSI behavior.The scores of ISI,GAD-7 and Adolescents Self-Harm Scale of senior high school students with suicidal ideation were higher than those of students without suicidal ideation(Z=17.124,20.611,21.314,P<0.01).As correlation analysis showed,the ISI score of senior high school students with suicidal ideation was positively correlated with scores of GAD-7 and Adolescents Self-Harm Scale(r=0.646,0.354,P<0.01),and GAD-7 score was positively correlated with the score of Adolescents Self-Harm Scale(r=0.375,P<0.01).Among senior high school students with suicide ideation,anxiety acted in a mediating role between insomnia and NSSI behavior,with effect value of 0.111(95%CI:0.053～0.185),accounting for 53.88%of the total effect.Conclusion Insomnia of senior high school students with suicidal ideation can not only directly affect NSSI behavior,but also indirectly affect NSSI behavior through anxiety.

Objective:To retrospectively analyze the surgical treatment of isolated pulmonary mucormycosis, explore the timing and effect of operation.Methods:Clinical data of patients with isolated pulmonary mucormycosis who underwent surgical treatment from April 2019 to April 2024 were collected and retrospectively analyzed, combined with literature review.Results:The clinical data of 13 patients with pulmonary mucormycosis who underwent operation were collected, including 9 males and 4 females, aged 22~64(45.4±15.4)years old. The basic diseases included diabetes mellitus in 10 cases and hematological malignancy in 3 cases. Seven patients had hemoptysis during the course of the disease. All 13 patients received adequate antifungal therapy before surgery, and 12 patients received bronchoscopic interventional therapy. Ten patients underwent lobectomy, two underwent pneumonectomy, and one underwent a right sleeve pneumonectomy. All patients were cured except one patient with bronchopleural fistula after operation. All patients achieved complete elimination of mucor and also discontinuation of antifungal drug.Conclusion:For isolated pulmonary mucormycosis, on the basis of systemic antifungal treatment, actively seek the opportunity of surgical intervention, can shorten the course of the disease and achieve good therapeutic results.

Objective To analyze the anesthetic effect and hemodynamic impact of oxybutynin(OBI)combined with dexmedetomidine(DEX)on patients undergoing endoscopic dacryocystorhinostomy(En-DCR).Methods Patients who underwent En-DCR from February 2024 to May 2024 at Mianyang Wanjiang Eye Hospital were recruited.They were randomly divided into the DEX group(DEX administration only)and the combined group(DEX combined with OLI administration)according to the random number table method.The primary observational index in this study was the 24-h postoperative pain numerical rating scale(NRS)scores.The secondary observation indexes were heart rate(HR),mean arterial pressure(MAP),respiratory recovery time(SRT),extubation time(ET)and awakening time(AT),peak systolic value(PSV),end-diastolic blood flow velocity(EDV),resistance index(RI)and blood flow(BF).The occurrence of adverse events in patients during hospitalization was observed and recorded.Results A total of 80 patients were included in the study,with 40 in each of the DEX group and the combined group.In terms of analgesia,the NRS scores in the combined group were lower than those in the DEX group at T1(within 0.5 h after catheter removal),T2(4 h postoperatively),T3(8 h postoperatively),and T4(24 h postoperatively)(P＜0.05),and the remedial analgesia rate in the combined group was significantly lower than that in the DEX group(P＜0.05).Regarding anesthetic effects,HR and MAP at time points T6(during induction of anesthesia),T7(intraoperatively)and T8(during resuscitation)were lower in the combined group than in the DEX group(P＜0.05);and SRT,ET and AT were shorter in the combined group compared with the DEX group(P＜0.05).In terms of hemodynamics,at 24 h postoperatively,PSV,EDV and BF were significantly higher in both groups compared with those before anesthesia,whereas RI was significantly lower than before anesthesia(P＜0.05);PSV,EDV and BF were higher in the combined group than those in the DEX group,and RI was lower than that in the DEX group(P＜0.05).Regarding adverse reactions,the incidence of adverse reactions in the combined group was significantly lower than that in the DEX group(P＜0.05).Conclusion OLI combined with DEX prophylactic analgesia for patients with En-DCR is effective,not only to reduce postoperative pain,stabilize hemodynamics,shorten the time of extubation and awakening,and reduce the incidence of adverse reactions.

That the property of peripheral pulmonary lesions(PPLs)is clarified need conduct biopsy,while it brings challenge for clinical diagnosis because the PPLs position stays away from the central airway and close to the pleura.Robotic bronchoscopy system is a new technique to help the diagnosis for pulmonary lesions,which can be used in navigation,positioning,biopsy and interventional treatment.Compared with conventional bronchoscopy,it is more stable and accurate,and it can reach farther and thinner inside of the airways.Moreover,the robotic bronchoscopy system can combine with many inspection equipment to further improve the accuracy of biopsy.At the same time,it has fewer complications than conventional percutaneous lung puncture biopsy.This article reviewed the development and application of robotic bronchoscopy,and prospected the combination of that and interventional therapy,which can provide more choices for PPLs biopsy method.

Objective To comprehensively characterize the diterpene alkaloids in Radix Aconiti Kusnezoffii.Methods The diterpene alkaloids were isolated and purified by strong acid cation exchange resin solid phase extraction column(SCX-SPE),and identified by ultra high performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS).Results A total of 99 diterpene alkaloids were identified from Radix Aconiti Kusnezoffii,including 27 diester diterpene alkaloids(DDA),29 monoester diterpene alkaloids(MDA),40 amide diterpene alkaloids(ADA),2 polyester diterpene alkaloids(PDA)and 1 long-chain ester diterpene alkaloid(LDA).Conclusion The SCX-SPE combined with UHPLC-Q-Exactive Orbitrap MS method,established in this paper,can rapidly identify a large number of diterpene alkaloids in Radix Aconiti Kusnezoffii,which provides scientific proof for the study of pharmacodynamic substance basis and quality control of Radix Aconiti Kusnezoffii.