Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

Objective To analyze the possible mechanism and drug treatment plan of diffuse alveolar hemorrhage induced by human granulocyte colony-stimulating factor injection, point out medication risks and provide reference for medical treatment and pharmaceutical care of such patients. Methods The abnormal lung conditions of a patient treated with human granulocyte colony-stimulating factor injection was found by clinical pharmacists, who participated in clinical diagnosis and treatment by analyzing of adverse drug reactions, optimization of medical treatment and pharmaceutical care. Results Diffuse alveolar hemorrhage was likely an adverse drug reaction caused by human granulocyte colony-stimulating factor injection. The physician discontinued the medication immediately and provided treatment such as oxygen inhalation, high-dose hormone shock, plasma exchange, etc. The patient’s oxygen saturation was improved, alveolar bleeding was decreased, and the condition was improved. Conclusion Clinical pharmacists participate in patients’ medication treatment, carry out pharmaceutical guardianship, and assist physicians in adjusting treatment plans, which could contribute to the effectiveness and safety of patient treatment.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Alternative splicing (AS) serves as a fundamental regulatory mechanism in gene expression, contributing to proteomic diversity by generating an array of mRNA isoforms from precursor mRNA via distinct splice site combinations. In light of the limited therapeutic options currently available, the exploration of AS as a target for drug development is of paramount importance. This review offers an exhaustive analysis of the biological functions and underlying molecular mechanisms associated with various AS-induced splice variants, RNA-binding proteins, and cis-elements, highlighting their significance as clinical biomarkers. We place particular emphasis on the current therapeutic applications of AS in an array of lung diseases, including but not limited to lung cancer, cystic fibrosis, silicosis, acute respiratory distress syndrome, pneumonia, asthma, chronic obstructive pulmonary diseases, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis. The review delves into the role of AS events in the diagnosis and treatment of lung diseases, focusing on the regulatory influence of splicing factors and RNA-binding proteins, while also enumerating the mutated components implicated in AS misregulation. Consequently, a comprehensive understanding of the intricate mechanisms governing these splicing events could potentially offer novel avenues for the development of splicing-targeted therapeutics and diagnostic tools for the prevention and treatment of lung diseases.

The pathogenesis of tinnitus is unclear and may involve the peripheral and central nervous sys-tems.Recent studies have found that neuroinflammatory response leads to hyperactivity of nerve center,in which tumor necrosis factor-α(TNF-α)has an important impact on neurotransmitter transmission,transmembrane ion concentration,neuronal synaptic structure and functional reorganisation,and may play an important role in the path-ogenesis of acute tinnitus.This article discusses the central mechanism of TNF-α in mediating the onset of acute tin-nitus.

Objective:To explore the diagnostic value of fractional flow reserve (FFR) based on optical coherence tomography (OCT) for coronary functional ischemia, and to investigate the feasibility of synchronously obtaining Doppler blood flow velocity information with the help of OCT technology.Methods:This study was a single-center, prospective, self-controlled clinical study on coronary heart disease patients who underwent OCT and FFR assessment at Department of Cardiology, the Second Hospital of Jilin University from January 2024 to February 2025. Linear regression analysis was used to evaluate the correlation and consistency between OCT-FFR and FFR. With FFR≤0.80 as the gold standard for judging whether the target vessel was ischemic, the diagnostic performance of OCT-FFR was evaluated, and the diagnostic value of OCT-FFR for significant coronary artery ischemia was assessed using subject operating characteristic curves. Blood flow OCT data were analyzed by Doppler processing algorithm to obtain information on coronary blood flow velocity.Results:A total of 31 vessels from 28 patients were analyzed, the correlation coefficient r between OCT-FFR and FFR of the 31 vessels was 0.84 ( P<0.001). With FFR as the gold standard to determine whether a coronary artery is ischemic, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for OCT-FFR was 93.55%, 75.00%, 100.00%, 1.00, 0.92. In clinical practice, Doppler OCT was used for the first time to obtain information on coronary blood flow velocity. Conclusion:OCT-FFR had an excellent correlation and consistency with FFR in judging whether there is coronary artery ischemia. The feasibility of the simultaneous acquisition of OCT-FFR and Doppler flow velocity information in coronary stenosis was preliminarily verified.

Objective:To investigate the epidemiological characteristics and trends of birth defects related to assisted reproductive technology (ART) in Jiangxi Province from 2014 to 2023, and to explore the correlation factors of birth defect occurrence.Methods:A retrospective collection of ART treatment data and follow-up results from January 2014 to December 2023 across 18 reproductive centers in Jiangxi Province was conducted. The trend of birth defects and the rank order of defect types were analyzed. Exact probability methods were used to estimate the 95% confidence intervals ( CI) of the incidence rates, and Poisson regression was applied to identify independent correlation factors. Results:A total of 65 003 ART offspring were included in this study, comprising 2 025 offspring from intrauterine insemination (IUI) and 62 978 from in vitro fertilization and embryo transfer (IVF-ET). The overall incidence of birth defects was 13.46‰ (95% CI: 12.59‰-14.38‰), with 9.38‰ (95% CI: 5.66‰-14.61‰) for IUI and 13.59‰ (95% CI:12.70‰-14.53‰) for IVF-ET. The incidence of birth defects showed a decreasing trend from 2014 to 2023 (17.11‰ to 11.47‰, Ptrend=0.003). The top three birth defect types were circulatory system defects (3.71‰, 95% CI: 3.25‰-4.21‰), musculoskeletal system defects (2.37‰, 95% CI: 2.01‰-2.77‰), and congenital malformations of the face, ears, eyes, and neck (1.23‰, 95% CI: 0.98‰-1.53‰). Univariate analysis indicated that male offspring from IVF-ET had a higher incidence of birth defects than that in female offspring (14.72‰ vs. 12.31‰, P=0.009). Additionally, gestational age, birth weight, fetal number, cause of infertility, and year of delivery were significantly associated with birth defect incidence in IVF-ET offspring ( P<0.001, P<0.001, P<0.001, P=0.025, P=0.037). Multivariate analysis showed that in singleton pregnancies, male offspring, gestational age 32-36 weeks birth weight <1 500 g, and infertility with bilateral factors were independent risk factors for birth defects ( OR=1.21, 95% CI: 1.00-1.47, P=0.046; OR=1.90,95% CI: 1.41-2.56, P<0.001; OR=3.37, 95% CI: 1.33-8.51, P=0.010; OR=1.38, 95% CI: 1.12-1.69, P=0.003), while in multiple pregnancies, male offspring, gestational age <32 weeks, gestational age 32-36 weeks, birth weight <1 500 g, birth weight 1 500-2 499 g, maternal age 25-29 years and maternal age 30-34 years were independent risk factors ( OR=1.25, 95% CI: 1.03-1.52, P=0.023; OR=2.06, 95% CI: 1.35-3.15, P=0.001; OR=1.32,95% CI: 1.05-1.66, P=0.016; OR=1.98,95% CI: 1.19-3.28, P=0.009; OR=2.06,95% CI: 1.64-2.60, P<0.001; OR=2.00, 95% CI: 1.31-3.06, P=0.001; OR=1.90,95% CI: 1.24-2.92, P=0.003). Conclusion:Over the past 10 years, the incidence of birth defects in ART offspring in Jiangxi Province has shown a decreasing trend annually, with circulatory system malformations being the most common. The occurrence of birth defects in IVF offspring is primarily associated with maternal and infant characteristics, such as gender, gestational age, birth weight, number of fetuses, and cause of infertility, independent of ART treatment factors.

Objective:To evaluate the efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator (short for "3M fixator") for Sanders types II and III calcaneal fractures.Methods:A retrospective case series study was conducted to analyze the clinical data of 26 patients (26 feet) with calcaneal fractures admitted to Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to June 2024, including 21 males and 5 females, aged 27-69 years [(46.5±2.5)years]. Among them, 10 patients had fractures in the left foot and 16 in the right. According to the Sanders classification, the fractures were classified as type II in 16 patients and type III in 10. All the patients were treated with the close reduction with reduction robot system combined with 3M fixator in a minimally invasive procedure. The surgical waiting time, operative duration, and fracture healing time were recorded. The length, width and height of the calcaneus, B?hler′s angle and Gissane′s angle were compared before operation and at 1, 3 months after operation. The visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score before operation and at 1, 3 months after operation and at the last follow-up were detected. The postoperative complications were recorded.Results:All the patients were followed up for 6-12 months [(9.7±1.1)months]. The surgical waiting time was 1-4 days [(2.0±0.8)days]. The operative duration was 36-66 minutes [(53.2±9.5)minutes]. All the fractures achieved primary union with a healing period of 3-4 months [(3.2±0.4)months]. At 1, 3 months after operation, the length of the calcaneus [(83.3±3.7)mm and (83.6±3.6)mm], width of the calcaneus [(44.3±5.8)mm and (44.3±5.7)mm], height of the calcaneus [(50.1±3.8)mm and (50.3±3.6)mm], B?hler′s angle [(29.8±2.9)° and (29.8±3.0)°], and Gissane angle [(121.1±6.7)° and (123.9±5.9)°] were significantly improved compared with those before operation [(79.3±4.5)mm, (53.6±4.1)mm, (46.2±3.7)mm, (18.9±3.8)°, (109.0±7.5)°, respectively] ( P<0.05), with no significant differences between those indicators at 1, 3 months after operation ( P>0.05). The VAS scores were (3.2±0.6)points, (1.9±0.5)points, and (1.6±0.3)points at 1, 3 months after operation and at the last follow-up, which were lower than (7.1±0.5)points preoperatively and decreased with the prolongation of follow-up time ( P<0.05). The AOFAS scores were (73.5±6.9)points, (90.1±4.3)points, and (92.0±3.6)points, which were higher than (32.0±4.6)points preoperatively and increased with the follow-up time ( P<0.05). One patient had lateral calcaneal pain after operation, and was alleviated after rehabilitation. No complications such as infection or nonunion were found after operation. Conclusion:The reduction robot system combined with 3M fixator for Sanders types II and III calcaneal fractures demonstrates significant clinical advantages, such as reduced surgical waiting time and operative duration, promoted fracture healing, early alleviated pain, enhanced ankle joint functional recovery, and decreased complication occurrence.

Objective:To analyze the epidemiological characteristics of human metapneumovirus（hMPV）in respiratory samples from patients in Suzhou，China，and investigate the results of whole-genome sequencing，so as to provide scientific evidence for a deeper understanding of its genetic diversity and the development of preventive measures.Methods:In this study，1 340 influenza-like illness（ILI）samples and 970 severe acute respiratory infection（SARI）samples were collected from two sentinel hospitals in Suzhou in 2024. Nucleic acid detection was performed using a multiplex real-time fluorescence PCR method. For hMPV-positive samples，whole-genome sequencing was conducted on the Illumina Miseq platform. Mutations，insertions，deletions，and other variations were identified using the pathogenic virus whole-genome analysis system. A phylogenetic tree was constructed by the Maximum Likelihood method for lineage analysis.Results:Among 2 310 respiratory samples，the overall hMPV positivity rate was 1.69%（39/2 310），with positivity rates of 1.27%（17/1 340）in ILI samples and 2.27%（22/970）in SARI samples. No statistically significant difference was observed between the two groups（ P>0.05）. The proportion of mixed infections in hMPV-positive samples was 46.15%（18/39），with mixed infection rates of 23.53%（4/17）in the ILI group and 63.64%（14/22）in the SARI group. In terms of temporal distribution，the peak period of hMPV infection primarily concentrated in January and December. The whole genomes of 13 hMPV strains were successfully obtained，and 554 missense mutations were identified in the coding region，with particularly significant variations observed in the G gene region. Phylogenetic analysis revealed that 4 strains belonged to the A2b2 subtype，while 9 strains belonged to the B2 subtype. Conclusions:In Suzhou，hMPV exhibits a relatively balanced distribution between ILI and SARI clinical groups，with infection peaks mainly occurring in winter and a high proportion of mixed infections. The predominant circulating strain is the B2 subtype，and its genome shows significant genetic variation，particularly in the G gene region.

OBJECTIVE To explore the diagnostic value of combined detection of microRNA(miRNA)and alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in ascites and serum ex-tracellular vesicles(EVs)for hepatitis B virus(HBV)-related primary hepatocellular carcinoma(HCC).METHODS From Nov.2023 to Nov.2024,41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chi-nese PLA General Hospital were selected as study subjects.Ascites and serum samples were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-21,miR-125a,miR-150 and miR-200a in EVs.Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites,serum and EVs from ascites and serum.An artificial neural network was utilized to con-struct a combined diagnostic model of serum and ascites markers.RESULTS The area under the curve(AUC)for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933.The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912.By screening all detected indicators using an artificial neural network and incorporating indicators with a relative im-portance＞0.5 into the diagnostic model,the model included four indicators:ascites AFP,ascites EVs miR-21,ascites EVs miR-200a and serum EVs miR-200a.This model had a sensitivity of 80.77％,a specificity of 87.80％and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.CONCLUSION The combined diagnos-tic markers of miRNA,AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.