Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

Musashi-2 potentiates colorectal cancer immune infiltration by regulating the post-translational modifications of HMGB1 to promote DCs maturation and migration.

Post-translational modifications (PTMs) of the non-histone protein high-mobility group protein B1 (HMGB1) are involved in modulating inflammation and immune responses. Recent studies have implicated that the RNA-binding protein (RBP) Musashi-2 (MSI2) regulates multiple critical biological metabolic and immunoregulatory functions. However, the precise role of MSI2 in regulating PTMs and tumor immunity in colorectal cancer (CRC) remains unclear. Here, we present data indicating that MSI2 potentiates CRC immunopathology in colitis-associated colon cancer (CAC) mouse models, cell lines and clinical specimens, specifically via HMGB1-mediated dendritic cell (DC) maturation and migration, further contributes to the infiltration of CD4+ and CD8+ T cells and inflammatory responses. Under stress conditions, MSI2 can exacerbate the production, nucleocytoplasmic transport and extracellular release of damage-associated molecular patterns (DAMPs)-HMGB1 in CRC cells. Mechanistically, MSI2 mainly enhances the disulfide HMGB1 production and protein translation via direct binding to nucleotides 1403-1409 in the HMGB1 3' UTR, and interacts with the cytoplasmic acetyltransferase P300 to upregulate its expression, further promoting the acetylation of K29 residue in HMGB1, thus leading to K29-HMGB1 nucleocytoplasmic translocation and extracellular release. Furthermore, blocking HMGB1 activity with glycyrrhizic acid (Gly) attenuates MSI2-mediated immunopathology and immune infiltration in CRC in vitro and in vivo. Collectively, this study suggests that MSI2 may improve the prognosis of CRC patients by reprogramming the tumor immune microenvironment (TIME) through HMGB1-mediated PTMs, which might be a novel therapeutic option for CRC immunotherapy.

Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion.

BACKGROUND: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown. METHODS: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected. RESULTS: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00). CONCLUSIONS: Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.

Small Things Make a Big Difference: Conductive Cross-Linking Sodium Alginate@MXene Binder Enables High-Volumetric-Capacity and High-Mass-Loading Li-S Battery.

Binders are crucial for maintaining the integrity of an electrode, and there is a growing need for integrating multiple desirable properties into the binder for high-energy batteries, yet significant challenges remain. Here, we successfully synthesized a new binder by cross-linking sodium alginate (SA) with MXene materials (Ti3C2Tx). Besides the improved adhesion and mechanical properties, the integrated SA@Ti3C2Tx binder demonstrates much improved electronic conductivity, which enables ruling out the fluffy conductive additive from the electrode component with enhanced volumetric capacity. When SA@Ti3C2Tx is used to fabricate sulfur (S) cathodes, the conductive-additive-free electrode demonstrates extremely high capacity (1422 mAh cm-3/24.5 mAh cm-2) under an S loading of 17.2 mg cm-2 for Li-S batteries. Impressively, the SA@Ti3C2Tx binder shows remarkable feasibility in other battery systems such as Na-S and LiFePO4 batteries. The proposed strategy of constructing a cross-linking conductive binder opens new possibilities for designing high-mass-loading electrodes with high volumetric capacity.

Musashi-2 Deficiency Triggers Colorectal Cancer Ferroptosis by Downregulating the MAPK Signaling Cascade to Inhibit HSPB1 Phosphorylation.

BACKGROUND: Musashi-2 (MSI2) is a critical RNA-binding protein (RBP) whose ectopic expression drives the pathogenesis of various cancers. Accumulating evidence suggests that inducing ferroptosis of tumor cells can inhibit their malignant biological behavior as a promising therapeutic approach. However, it is unclear whether MSI2 regulates cell death in colorectal cancer (CRC), especially the underlying mechanisms and biological effects in CRC ferroptosis remain elusive. METHODS: Experimental methods including qRT‒PCR, immunofluorescence, flow cytometry, western blot, co-immunoprecipitation, CCK-8, colony formation assay, in vitro cell transwell migration and invasion assays, in vivo xenograft tumor experiments, liver and lung CRC metastasis models, CAC mice models, transmission electron microscopy, immunohistochemistry, histopathology, 4D label-free proteomics sequencing, bioinformatic and database analysis were used in this study. RESULTS: Here, we investigated that MSI2 was upregulated in CRC and positively correlated with ferroptosis inhibitor molecules. MSI2 deficiency suppressed CRC malignancy by inhibiting cell proliferation, viability, migration and invasion in vitro and in vivo; and MSI2 deficiency triggered CRC ferroptosis by changing the intracellular redox state (ROS levels and lipid peroxidation), erastin induced cell mortality and viability, iron homeostasis (intracellular total irons and ferrous irons), reduced glutathione (GSH) levels and mitochondrial injury. Mechanistically, through 4D-lable free proteomics analysis on SW620 stable cell lines, we demonstrated that MSI2 directly interacted with p-ERK and MSI2 knockdown downregulated the p-ERK/p38/MAPK axis signaling pathway, which further repressed MAPKAPK2 and HPSB1 phosphorylation, leading to decreased expression of PCNA and Ki67 and increased expression of ACSL4 in cancer cells. Furthermore, HSPB1 could rescue the phenotypes of MSI2 deficiency on CRC ferroptosis in vitro and in vivo. CONCLUSIONS: This study indicates that MSI2 deficiency suppresses the growth and survival of CRC cells and promotes ferroptosis by inactivating the MAPK signaling pathway to inhibit HSPB1 phosphorylation, which leads to downregulation of PCNA and Ki67 and upregulation of ACSL4 in cancer cells and subsequently induces redox imbalance, iron accumulation and mitochondrial shrinkage, ultimately triggering ferroptosis. Therefore, targeted inhibition of MSI2/MAPK/HSPB1 axis to promote ferroptosis might be a potential treatment strategy for CRC.

Enhanced Chemodynamic Therapy Mediated by a Tumor-Specific Catalyst in Synergy with Mitophagy Inhibition Improves the Efficacy for Endometrial Cancer.

Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H2 O2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H2 O2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1)high catalase (CAT)low therapeutic window for the use of NQO1 bioactive drug ß-lapachone (ß-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes ß-Lap to produce excess H2 O2 and initiate oxidative stress, which selectively suppress NQO1high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis. Moreover, shRNA-mediated NQO1 knockdown or dicoumarol rescues NQO1high EC cells from ß-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal-organic frameworks (MOF(Fe)) further promote the conversion of the accumulated H2 O2 into highly oxidative ·OH, which in turn, exacerbates the oxidative damage to RGD-positive target cells. Furthermore, mitophagy inhibition by Mdivi-1 blocks a powerful antioxidant defense approach, ultimately ensuring the anti-tumor efficacy of stepwise-amplified reactive oxygen species signals. The tumor growth inhibition rate (TGI) is about 85.92%. However, the TGI of MOF(Fe)-based synergistic antitumor therapy decreases to only 50.46% in NQO1-deficient KLE tumors. Tumor-specific chemotherapy and CDT-triggered therapeutic modality present unprecedented therapeutic benefits in treating NQO1high EC.

Introducing of Cu(I) in MOFs by In Situ Reduction with Ni as the Catalyst for Efficient Olefin/Paraffin Separation.

Olefins can be cracked to provide more low-carbon olefins than paraffins; therefore, separation of olefin/paraffin mixtures is essential for arranging hydrocarbon molecules for directed conversion. In this article, a simple approach for reducing copper atoms in Cu-BTC has been developed to improve olefin/paraffin adsorption capacity and selectivity. Considering that Cu-BTC shows adsorption benefits, its olefin/paraffin adsorption and separation performance were improved further by in situ reduction of Cu(II) to Cu(I) in Cu-BTC using ethanol as the reducing agent and nickel ions as the catalyst. The results revealed that during the reduction process, Cu ion conversion from tetra-ligand to diligand considerably increased their specific surface area, resulting in more active adsorption sites inside the modified sample. The ratio of Cu(I)/Cu(II) in the modified samples varied from 0.57 to 0.96. When Cu(II) of Cu-BTC was reduced to Cu(I), the adsorption capacities of 1-hexene increased from 145.97 to 243.65 mg/g, whereas n-hexane adsorption increased only slightly from 8.18 to 11.43 mg/g, resulting in an acceptable increase in selectivity from 17.84 to 21.32. Cu-BTC, due to its own Cu atoms, minimizes the substantial requirements for the synthesis process as well as the oxygen avoidance conditions for storage when monovalent copper is introduced, compared to other porous materials. Experimental results found that when Cu(I) was introduced, the Lewis acidic sites of the modified Cu-BTC material were increased, and Cu(I) has an electrical structure that makes it susceptible to both accepting and donating too many d electrons, resulting in a stronger adsorption of olefins containing π-electrons to them. Materials Studio simulation revealed that the isosteric heats of modified Cu-BTC increased by 2.7 kJ/mol, indicating that it has a stronger adsorption capacity for olefins.

Quality of life in patients with cervical cancer between the Han nationality and ethnic minorities in the Yunnan Province of China.

BACKGROUND: Cervical cancer is the fourth most diagnosed cancer and the leading cause of cancer death, and it still poses a crippling threat to women's health. China launched the National Cervical Cancer Screening Program for Rural Women in 2009, and an increasing number of cervical cancer patients have been detected. Health-related quality of life is not only the end point of cancer research but is also related to socioeconomic and clinical factors and has received an increasing amount of attention. In light of the characteristics of the Yunnan nationality, we conducted cross-sectional research to assess and explore the health-related quality of life in both Han and ethnic minority patients. METHODS: A cross-sectional study was conducted from January 2020 to May 2021 at the Third Affiliated Hospital of Kunming University/Yunnan Cancer Hospital. Patients, including 100 Han patients and 100 ethnic minorities, were interviewed using the FACT-Cx questionnaire within 3 months of receiving treatment. RESULTS: Patients of Han ethnicity and ethnic minorities were comparable in both sociodemographic and clinical features. The total FACT-Cx scores were 139.38 ± 9.83 and 134.39 ± 13.63 in Han and ethnic minority patients, respectively (P < 0.05). Significant differences were shown in physical well-being, emotional well-being and the FACT-Cx subscale between the Han and ethnic minority groups. Independent predictors of the FACT-Cx scale were ethnicity, educational level, participation in the National Cervical Cancer Screening Program for Rural Areas (NCCSPRA) and clinical stage. CONCLUSIONS: The results of our study imply that the HRQOL of Han patients is better than that of ethnic minority patients. Thus, clinicians and related health workers should pay more attention to the HRQOL of cervical cancer patients, especially for ethnic minority patients, and provide psychosocial interventions as much as possible to improve their HRQOL. Policies should also aim to strengthen health education regarding cervical cancer and expand the coverage of the NCCSPRA among those who are ethnic minorities, are older and have low educational levels.

A scoring model based on clinical factors to predict postoperative moderate to severe acute respiratory distress syndrome in Stanford type A aortic dissection.

BACKGROUND: Postoperative acute respiratory distress syndrome (ARDS) after type A aortic dissection is common and has high mortality. However, it is not clear which patients are at high risk of ARDS and an early prediction model is deficient. METHODS: From May 2015 to December 2017, 594 acute Stanford type A aortic dissection (ATAAD) patients who underwent aortic surgery in Anzhen Hospital were enrolled in our study. We compared the early survival of MS-ARDS within 24 h by Kaplan-Meier curves and log-rank tests. The data were divided into a training set and a test set at a ratio of 7:3. We established two prediction models and tested their efficiency. RESULTS: The oxygenation index decreased significantly immediately and 24 h after TAAD surgery. A total of 363 patients (61.1%) suffered from moderate and severe hypoxemia within 4 h, and 243 patients (40.9%) suffered from MS-ARDS within 24 h after surgery. Patients with MS-ARDS had higher 30-day mortality than others (log-rank test: p-value <0.001). There were 30 variables associated with MS-ARDS after surgery. The XGboost model consisted of 30 variables. The logistic regression model (LRM) consisted of 11 variables. The mean accuracy of the XGBoost model was 70.7%, and that of the LRM was 80.0%. The AUCs of XGBoost and LRM were 0.764 and 0.797, respectively. CONCLUSION: Postoperative MS-ARDS significantly increased early mortality after TAAD surgery. The LRM model has higher accuracy, and the XGBoost model has higher specificity.

[Simulation design and experimental study of magnetic stimulation coil for robot pigeon].

To explore the feasibility of applying magnetic stimulation technology to the movement control of animal robots, the influence of coil radius, number of turns and other factors on the intensity, depth and focus of magnetic stimulation was simulated and analyzed for robot pigeons. The coil design scheme was proposed. The coil was placed on the head and one of the legs of the pigeon, and the leg electromyography (EMG) was recorded when magnetic stimulation was performed. Results showed that the EMG was significantly strengthened during magnetic stimulation. With the reduction of the output frequency of the magnetic stimulation system, the output current was increased and the EMG was enhanced accordingly. Compared with the brain magnetic stimulation, sciatic nerve stimulation produced a more significant EMG enhancement response. This indicated that the magnetic stimulation system could effectively modulate the functions of brain and peripheral nerves by driving the coil. This study provides theoretical and experimental guidance for the subsequent optimization and improvement of practical coils, and lays a preliminary theoretical and experimental foundation for the implementation of magnetic stimulation motion control of animal robots.

Transcriptome and Quasi-Targeted Metabolome Analyze Overexpression of 4-Hydroxyphenylpyruvate Dioxygenase Alleviates Fungal Toxicity of 9-Phenanthrol in Magnaporthe oryzae.

Magnaporthe oryzae, the causal agent of rice blast disease, produces devastating damage to global rice production. It is urgent to explore novel strategies to overcome the losses caused by this disease. 9-phenanthrol is often used as a transient receptor potential melastatin 4 (TRPM4) channel inhibitor for animals, but we found its fungal toxicity to M. oryzae. Thus, we explored the antimicrobial mechanism through transcriptome and metabolome analyses. Moreover, we found that overexpression of a gene encoding 4-hydroxyphenylpyruvate dioxygenase involved in the tyrosine degradative pathway enhanced the tolerance of 9-phenanthrol in M. oryzae. Thus, our results highlight the potential fungal toxicity mechanism of 9-phenanthrol at metabolic and transcriptomic levels and identify a gene involving 9-phenanthrol alleviation. Importantly, our results demonstrate the novel mechanism of 9-phenanthrol on fungal toxicity that will provide new insights of 9-phenanthrol for application on other organisms.

Influence of Dynamic and Static Obstructive Renal Artery on Early Prognosis in Stanford Type A Aortic Dissection.

BACKGROUND: Acute kidney injury (AKI) after acute Stanford type A aortic dissection (STAAD) surgery has a high mortality rate. Clarifying what type of renal artery problem (dynamic obstructive renal artery, DORA, or static obstructive renal artery, SORA) secondary to STAAD benefits from true lumen opening is helpful in providing a reference for the indication of renal artery intervention. METHODS: From May 2018 to December 2019, 292 acute STAAD patients who underwent aortic surgery were enrolled in this study. DORA, SORA, and renal malperfusion were diagnosed according to preoperative aortic enhanced computed tomography (CTA). Renal artery problems secondary to STAAD were divided into three types: type 1, normal renal artery; type 2, DORA; and type 3, SORA. Acute kidney injury was divided into three stages: Stage 1, Stage 2, and Stage 3, according to 2012 Kidney Disease: Improving Global Outcomes (KDIGO). The primary endpoint was all-cause 30-day in-hospital death, and the secondary endpoint was postoperative dialysis requirement. Univariate and multivariate analyses were performed to assess the difference among the three types. RESULTS: Postoperative AKI occurred in 154 of 292 (52.7%) patients, and postoperative dialysis was present in 27 of 292 (9.2%) patients with STAAD. Postoperative AKI and dialysis were significantly more prevalent in the SORA group (AKI: 71% in SORA group vs 51.5% in DORA group vs 22.2% in normal group; postoperative dialysis: 22.2% in SORA group vs 5.4% in DORA group vs 6.1 in normal group). Thirty-day (30-day) mortality was also significantly higher in the SORA group (Log-rank test, p=0.012). Preoperative acute myocardial infarction and body mass index were the independent risk factors for 30-day mortality. Static obstructive renal artery, cardiopulmonary bypass time, and renal blood cell transfusion >3 units were the independent risk factors for postoperative dialysis requirement. CONCLUSION: Static obstructive renal artery led to higher 30-day in-hospital mortality and more postoperative dialysis. Open surgery reduced renal ischaemia injury caused by DORA, but it could not reduce renal ischaemia injury caused by SORA.

Extracts of Knoxia roxburghii (Spreng.) M. A. Rau Induce Apoptosis in Human MCF-7 Breast Cancer Cells via Mitochondrial Pathways.

Knoxia roxburghii (Spreng.) M. A. Rau (KR) is a plant clinically used in traditional Chinese medicine (TCM) for the treatment of cancer. The study objectives were to examine the effects of KR extracts, petroleum ether (PET), ethyl acetate (EtoAc), butanol (n-BuOH), and H2O-soluble fractions (HSF) of the 75% EtOH extraction on A549 (non-small cell lung cancer), HepG2 (liver cancer), HeLa (cervical cancer), MCF-7 (breast cancer), and L02 (normal hepatocyte) cells. It was found that HSF exhibited the strongest cytotoxic activity against MCF-7 cells, and was accompanied by reduced mitochondrial transmembrane potential, increased levels of intra-cellular reactive oxygen species (ROS) and activated caspases, and upregulated pro-apoptotic and downregulated anti-apoptotic proteins. LC-MS analysis further showed that HSF primarily consisted of calycosin, aloe emodin, rein, maackiain, asperuloside, orientin, vicenin-2, and kaempferide, which have been mostly reported for anti-tumor activity in previous studies. In summary, the current study illustrated the effect, mechanism, and the potential major active components of KR against breast cancer.

The quality of life in women with cervical cancer and precancerous lesions of Han and ethnic minorities in Southwest China.

BACKGROUND: As patients with cervical cancer and precancerous lesions can be diagnosed at early stage and live longer, it is imperative to understand their health-related quality of life so that better cancer-related policies could be promoted and reasonable distribution of limited resources could be implemented. We conducted a cross-sectional study in the Third Affiliated Hospital of Kunming Medical University to assess the health-related quality of life in our targeted population. Due to the characteristics of Yunnan nationality, our study population includes both Han people and ethnic minorities. METHODS: A cross-sectional study was conducted from January 2019 to December 2020, and 300 patients were selected, who were initially diagnosed with cervical cancer and cervical intraepithelial neoplasia (CIN) pathologically. EQ-5D questionnaire was used to evaluate their quality of life. RESULTS: Patients in Han and ethnic minorities showed good comparability. EQ-5D VAS score was statistically significant between Han and ethnic minorities (mean, 85.42 vs. 81.01; P<0.05). EQ-5D utility score was slightly different but without statistical significance between the two groups (mean, 0.959 vs. 0.932; P>0.05). Nationality, economic trouble, menopause status and participation of China National Cervical Cancer Screening Program (CNCCSP) are influencing factors of HRQoL among women with cervical cancer and precancerous lesions. Besides, we also found low awareness in the CNCCSP and human papilloma virus vaccine, as well as low participation in the national screening program. CONCLUSION: The results of our study imply that the difference of HRQoL does exist between Han people and ethnic minorities with cervical cancer and precancerous lesions. Health providers and health-related departments need to invest more health and financial resources to expand the awareness and participation of the screening project. More efforts should be made in underdeveloped minority areas to assure the accessibility of health resources and interventions. To mitigate economic trouble caused by the diseases, more equal insurance reimbursement should be suggested and implemented in people with or without employee insurance.

Emergency percutaneous thoracic endovascular aortic repair for patients with traumatic thoracic aortic blunt injury: A single center experience.

PURPOSE: To analyze the efficacy and outcome of percutaneous thoracic endovascular aortic repair (TEVAR) in patients with traumatic blunt aortic injury in our single-center. METHODS: From January 2014 to December 2018, a total of 89 patients with traumatic blunt aortic injuries were treated with emergency TEVAR in our center. Their clinical data such as demographics, operative details and postprocedure outcomes were analyzed retrospectively in this study using SPSS 20 software. Continuous variables were expressed as mean and standard deviation or median and interquartile range. Categorical variables are expressed as the numbers and percentages of patients. RESULTS: The median age of the patients was 37 years, and 76 (85.4%) were males. All the patients were involved in violent accidents and combined with associated injuries. Two patients died while awaiting the operations and 87 patients underwent emergency percutaneous TEVAR, with a 100% technique success. The mean time interval from admission to operating room was (90.1 ± 18.7) min, and the mean procedure time was (54.6 ± 11.9) min. Eighty (92.0%) patients were operated on under local anesthesia, while other 7 (8.0%) patients were under general anesthesia. Two cases underwent open repair of the femoral arteries because of the pseudoaneurysm formation of the access vessels. A total of 98 aortic covered stent grafts were deployed, of which 11 patients used two stent grafts (all in dissection cases). The length of the stent was (177.5 ± 24.6) mm. The horizontal diameter of aorta arch at the proximal left subclavian artery ostium was (24.9 ± 2.4) mm, the proximal diameter of the covered stent was (30.5 ± 2.6) mm, and the oversize rate of proximal site was (22.7 ± 4.0)%. The proximal landing zone length was (14.1 ± 5.5) mm. The left subclavian artery ostium was completely covered in 5 patients and partially covered in 32 patients. No blood flow reconstruction was performed. The overall aortic-related mortality was 2.25% (2/89). Among 87 patients, the median follow-up time was 24 months. Postoperative computed tomography angiography scans demonstrated no residual pseudoaneurysm, hematoma or endoleak. One patient complained of mild left upper limb weakness during follow-up due to left subclavian artery occlusion. Neither late death, nor neurological or other complications occurred. CONCLUSION: Emergency percutaneous endovascular repair is a less invasive and effective approach for the treatment of traumatic blunt aortic injuries. Long-term results remain to be further followed.

Pharmacogenomics research: a potential strategy for drug development.

Adverse drug reactions (ADR) and drug ineffectiveness are the common in clinical practice. Recent studies have indicated their strong connection to the genetic feature of patients. To further illustrate this relationship, the discipline of Pharmacogenomics (PGx) was born. At present, in vitro cell models and in vivo transgenic animal models have a large potential to study the influence of human genetic mutations on drug response. Moreover, PGx guided clinical trials also provide benefits to drug development. With the drug targets introduced by PGx, great success has been achieved in targeted therapy (eg. gefitinib, cetuximab and ado-trastuzumab). Although the progress on PGx research is fascinating, the translation of PGx into drug development is unsatisfactory. To improve this situation, a rounded system that includes individuals, medical staff, academics associations, Government and Pharmaceutics-Biotechnology Industry should be established, as well as a connected pipeline consisting of policy guidance, PGx research, genotyping technology, preclinical and clinical studies.

Isocentric fixed angle irradiation-based DRR: a novel approach to enhance x-ray and CT image registration.

Objective.Digitally reconstructed radiography (DRR) plays an important role in the registration of intraoperative x-ray and preoperative CT images. However, existing DRR algorithms often neglect the critical isocentric fixed angle irradiation (IFAI) principle in C-arm imaging, resulting in inaccurate simulation of x-ray images. This limitation degrades registration algorithms relying on DRR image libraries or employing DRR images (DRRs) to train neural network models. To address this issue, we propose a novel IFAI-based DRR method that accurately captures the true projection transformation during x-ray imaging of the human body.Approach.By strictly adhering to the IFAI principle and utilizing known parameters from intraoperative x-ray images paired with CT scans, our method successfully simulates the real projection transformation and generates DRRs that closely resemble actual x-ray images.Main result.Experimental results validate the effectiveness of our IFAI-based DRR method by successfully registering intraoperative x-ray images with preoperative CT images from multiple patients who underwent thoracic endovascular aortic procedures.Significance. The proposed IFAI-based DRR method enhances the quality of DRR images, significantly accelerates the construction of DRR image libraries, and thereby improves the performance of x-ray and CT image registration. Additionally, the method has the generality of registering CT and x-ray images generated by large C-arm devices.

Effect of different starting doses of FSH on laboratory and clinical outcomes in patients with moderate AMH level.

BACKGROUND: IVF and ICSI-ET are widely used ART for addressing infertility which have been developed and improved over the last four decades. COS is a crucial step in IVF/ICSI-ET, whereby medications stimulate the ovaries to produce multiple eggs. The success of the procedure depends on the number of eggs retrieved, and individualized ovarian stimulation protocols based on factors like age and ovarian reserve can optimize the chances of obtaining mature oocytes. The optimal starting dose of FSH at moderate AMH levels remains a topic of debate., tThis study aims to compare different starting doses of FSH in clinical outcomes by analyzing data from a single center. METHODS: This retrospective study collected clinical material from patients with moderate AMH levels at 1.2 ~ 4.5 ng/mL who received IVF/ICSI-ET under a follicular phase long protocol from July 2018 to December 2021 at Guiyang Maternal and Child Health Care Hospital, China. The patients' clinical data were retrieved from the hospital's software database and divided into two groups based on FSH starting dose, as follows: lower starting dose group: FSH ≤ 150 IU; and higher starting dose group: FSH > 150 IU. Multiple laboratory and clinical outcomes were compared between the two groups. RESULTS: A total of 1784 patients with moderate serum AMH levels who received IVF/ICSI-ET under a follicular phase long protocol were enrolled based on eligibility criteria. In the population with moderate AMH levels, a lower starting dose of FSH might have more benefit than a higher starting dose in numbers of follicles with diameters ≥ 14 mm and < 16 mm, ≥ 16 mm and < 18 mm, and ≥ 18 mm; numbers of retrieved oocytes, 2PNs, transferable embryos, high-quality embryos, and cleavage stage embryos transferred; and clinical pregnancy rate, intrauterine pregnancy rate, and parturition rate. Moreover, rFSH had a statistically significantly higher number of oocytes retrieved, number of 2PNs, and number of transferable embryos than that of patients who received uFSH. CONCLUSIONS: The starting dose of FSH in the moderate AMH population remains controversial and a higher starting dose may not lead to more benefit in laboratory and clinical outcomes.

Synergistic Cation-π Interactions and PEDOT-Based Protective Double-Layer for High Performance Zinc Anode.

Ensuring effective and controlled zinc ion transportation is crucial for functionality of the solid electrolyte interphase (SEI) and overall performance in zinc-based battery systems. Herein the first-ever demonstration of incorporate cation-π interactions are provided in the SEI to effectively facilitate uniform zinc ion flux. The artificial SEI design involves the immobilization of 4-amino-p-terphenyl (TPA), a strong amphiphilic cation-π interaction donor, as a monolayer onto a conductive poly(3,4-ethylenedioxythiophene) (PEDOT) matrix, which enable the establishment of a robust network of cation-π interactions. Through a carefully-designed interfacial polymerization process, a high-quality, large-area, robust is achieved, thin polymeric TPA/PEDOT (TP) film for the use of artificial SEI. Consequently, this interphase exhibits exceptional cycling stability with low overpotential and enables high reversibility of Zn plating/stripping. Symmetrical cells with TP/Zn electrodes can be cycled for more than 3200 hours at 1 mA cm-2 and 1 mAh cm-2 . And the asymmetric cells can cycle 3000 cycles stably with a high Coulomb efficiency of 99.78%. Also, under the extreme conditions of lean electrolyte and low N/P ratio, the battery with TP protective layer can still achieve ultra-stable cycle.

From antioxidant defense to genotoxicity: Deciphering the tissue-specific impact of AgNPs on marine clam Ruditapes philippinarum.

The escalating use of silver nanoparticles (AgNPs) across various sectors for their broad-spectrum antimicrobial capabilities, has raised concern over their potential ecotoxicological effects on aquatic life. This study explores the impact of AgNPs (50 µg/L) on the marine clam Ruditapes philippinarum, with a particular focus on its gills and digestive glands. We adopted an integrated approach that combined in vivo exposure, biochemical assays, and transcriptomic analysis to evaluate the toxicity of AgNPs. The results revealed substantial accumulation of AgNPs in the gills and digestive glands of R. philippinarum, resulting in oxidative stress and DNA damage, with the gills showing more severe oxidative damage. Transcriptomic analysis further highlights an adaptive up-regulation of peroxisome-related genes in the gills responding to AgNP-induxed oxidative stress. Additionally, there was a noteworthy enrichment of differentially expressed genes (DEGs) in key biological processes, including ion binding, NF-kappa B signaling and cytochrome P450-mediated metabolism of xenobiotics. These insights elucidate the toxicological mechanisms of AgNPs to R. philippinarum, emphasizing the gill as a potential sensitive organ for monitoring emerging nanopollutants. Overall, this study significantly advances our understanding of the mechanisms driving nanoparticle-induced stress responses in bivalves and lays the groundwork for future investigations into preventing and treating such pollutants in aquaculture.