Investigating the clinical role and prognostic value of genes related to insulin-like growth factor signaling pathway in thyroid cancer.

BACKGROUND: Thyroid cancer (THCA) is the most common endocrine malignancy having a female predominance. The insulin-like growth factor (IGF) pathway contributed to the unregulated cell proliferation in multiple malignancies. We aimed to explore the IGF-related signature for THCA prognosis. METHOD: The TCGA-THCA dataset was collected from the Cancer Genome Atlas (TCGA) for screening of key prognostic genes. The limma R package was applied for differentially expressed genes (DEGs) and the clusterProfiler R package was used for the Gene Ontology (GO) and KEGG analysis of DEGs. Then, the un/multivariate and least absolute shrinkage and selection operator (Lasso) Cox regression analysis was used for the establishment of RiskScore model. Receiver Operating Characteristic (ROC) analysis was used to verify the model's predictive performance. CIBERSORT and MCP-counter algorithms were applied for immune infiltration analysis. Finally, we analyzed the mutation features and the correlation between the RiskScore and cancer hallmark pathway by using the GSEA. RESULT: We obtained 5 key RiskScore model genes for patient's risk stratification from the 721 DEGs. ROC analysis indicated that our model is an ideal classifier, the high-risk patients are associated with the poor prognosis, immune infiltration, high tumor mutation burden (TMB), stronger cancer stemness and stronger correlation with the typical cancer-activation pathways. A nomogram combined with multiple clinical features was developed and exhibited excellent performance upon long-term survival quantitative prediction. CONCLUSIONS: We constructed an excellent prognostic model RiskScore based on IGF-related signature and concluded that the IGF signal pathway may become a reliable prognostic phenotype in THCA intervention.

Effects of laparoscopic radical prostatectomy on wound infection of surgery in patients with prostate cancer: A meta-analysis.

This meta-analysis aims to comprehensively assess the impact of laparoscopic radical prostatectomy (LRP) on wound infection in patients with prostate cancer (PCa). A systematic search was conducted, from database inception to November 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) comparing LRP with open radical prostatectomy (ORP) in the treatment of PCa. Two researchers independently screened the literature, extracted data and conducted quality assessments based on pre-defined inclusion and exclusion criteria. Stata 17.0 software was employed for data analysis. Overall, 15 RCTs involving 1458 PCa patients were included. The analysis revealed the incidence of wound infection (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.16-0.51, p < 0.001) and complications (OR = 0.27, 95% CI = 0.20-0.37, p < 0.001) was significantly lower in the LRP group compared to the ORP group. This study demonstrates that LRP in PCa patients can effectively reduce the incidence of wound infections and complications, indicating significant therapeutic efficacy and justifying its broader clinical application.

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP).

Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents an emerging paradigm for infectious disease control. In this scheme, a combination of a high efficacy and low solubility of anti-infection drugs permits the establishment of a pharmaceutical firewall in HIV-vulnerable groups over a long period. Although the structure-activity-relationship (SAR) of cabotegravir as an INSTI is known, the structural determinants of its low solubility have not been identified. In this work, we have integrated multiple experimental and computational methods, namely X-ray diffraction, solid-state NMR (SSNMR) spectroscopy, solution NMR spectroscopy, automated fragmentation (AF)-QM/MM and density functional theory (DFT) calculations, to address this question. The molecular organization of cabotegravir in crystal lattice has been determined. The combination of very-fast magic-angle-sample-spinning (VF MAS) SSNMR and solution NMR, as supported by AF-QM/MM and DFT calculations, permits the identification of structural factors that contribute to the low aqueous solubility of cabotegravir. Our study reveals the multitasking nature of pharmacophores in cabotegravir, which controls the drug solubility and, meanwhile, the biological activity. By unraveling these function-defining molecular features, our work could inspire further development of long-acting HIV PrEP drugs.

A real-world pharmacovigilance study of FDA adverse event reporting system events for sildenafil.

BACKGROUND: Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is widely used for the treatment of erectile dysfunction (ED). However, the safety profile of sildenafil, including adverse event (AEs), requires comprehensive evaluation. METHODS: This retrospective pharmacovigilance study aimed to evaluate AEs linked to sildenafil by analyzing data sourced from the FDA Adverse Event Reporting System (FAERS) database. A case/non-case design was utilized, and various algorithms including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) were employed to measure the signals indicating the presence of sildenafil-related AEs. RESULTS: Among 339,230 reports, 33,692 specifically mentioned sildenafil use. Most of AEs occurred in males over 60 years old. The United States accounted for the highest proportion of reported AEs. Severe outcomes, including death, disability, and life-threatening events, were reported. Significant system organ class (SOC) included "Reproductive system and breast disorders" (SOC: 10038604), "Neoplasms benign, malignant and unspecified" (SOC: 10038738), "Vascular disorders" (SOC: 10047065), and "Blood and lymphatic system disorders" (SOC: 10005329). Noteworthy preferred terms (PTs) associated with sildenafil included "Vision blurred," "Flushing," "sudden hearing loss," "Painful erection," and "Priapism." Unexpected AEs, such as "Malignant melanoma," "Pulmonary hypertension," "Malignant melanoma in situ," "Pulmonary arterial hypertension," "Metastatic malignant melanoma," "Malignant melanoma stage III," "Malignant melanoma stage II," "Acquired hemophilia," "Aortic dissection rupture," and "Intracranial artery dissection" were also identified. CONCLUSIONS: These findings emphasize the importance of monitoring and understanding the potential risks associated with sildenafil. Further investigation is warranted to validate these associations and address previously unrecognized safety concerns.

Repairing of recurrent leg ulcer induced by hydroxyurea with posterior tibial artery perforator propeller flap: Case report.

INTRODUCTION AND IMPORTANCE: Hydroxyurea is a cytotoxic drug commonly used to treat various myeloproliferative disorders. However, prolonged oral administration of this drug may trigger skin side effects and ulcers. There are few clinical reports on treating leg ulcers caused by hydroxyurea and even fewer clinical reports on managing recurrent ulcers after treatment. CASE PRESENTATION: An 87-year-old woman with essential thrombocythemia presented with a painful skin ulcer on her left calf. After failed outpatient treatment, she opted for hospitalisation for free skin grafting. Four months later, ulcers reappeared at the transplant site, leading to her readmission to the hospital. The diagnosis revealed that the leg ulcers were caused by hydroxyurea. Despite this, she persisted with hydroxyurea treatment and subsequently underwent posterior tibial artery perforator flap surgery. During the two-year follow-up, a new ulcer developed on the medial condyle of her other calf. However, no new ulcers or local pain were observed in the area where perforator flap grafting was performed. CLINICAL DISCUSSION: Leg ulcers caused by hydroxyurea are rare clinically and can easily be misdiagnosed. There is currently minimal research on ulcer recurrence after treatment. Posterior tibial perforator flaps may more effectively promote the healing of recurrent ulcers. CONCLUSION: Compared to conservative treatment and skin grafting surgery, the posterior tibial artery perforator flap offers a dependable blood supply and enhances the likelihood of wound healing. It can be considered an option, particularly for recurrent and refractory ulcers, even without discontinuing medication.

Flow diverter tail malapposition after implantation in the internal carotid artery for aneurysm treatment: a preliminary study.

Background and purpose: Favorable wall apposition of a flow diverter (FD) is essential for the treatment of intracranial aneurysms. The irretrievability and final drop point uncertainty of the proximal tail of the FD increase the difficulty of achieving good tail apposition. Therefore, understanding the factors associated with FD tail malapposition would be helpful for clinical practice. Methods: A total of 153 patients with 161 FD deployments in the carotid artery between 2020 and 2023 were retrospectively collected from our center's database for this study. Patient demographics, aneurysm characteristics, FDs, carotid artery anatomy, periprocedural complications, discharge modified Rankin scale (MRS) scores, and follow-up outcomes were investigated by comparing patients with and without FD tail malapposition. Comparisons were made with t tests or Kruskal-Wallis tests for continuous variables and the Pearson χ2 or Fisher exact test for categorical variables. Logistic regression was conducted to determine the predictors of malapposition. Results: Tail malapposition occurred for 41 out of the 161 FDs (25.5%). Univariate analysis revealed that the FD brand, FD length, FD distal to proximal vessel diameter ratio, FD tail position (straight or curved), and curvature of the vessel curve were significantly associated with FD tail malapposition (p < 0.05). Further multivariate analysis demonstrated that the application of a surpass FD (p = 0.04), the FD distal to proximal vessel diameter ratio (p = 0.022), the FD tail position (straight or curved) (p < 0.001) and the curvature of the vessel curve (p < 0.001) were factors significantly associated with FD tail malapposition. No significant difference was found in periprocedural or follow-up outcomes. The classification of FD tail malapposition was determined from imaging. The two major patterns of FD tail malapposition are unattached tails and protrusive tails. Conclusion: FD tail malapposition might be associated with a larger FD distal to the proximal vessel diameter difference, a curved vessel where the FD tail is located, and a larger curvature of the vessel curve. FD tail malapposition can be classified into unattached tails and protrusive tails, which have their own characteristics and should be noted in clinical practice.

Intelligent Nanoplatform Integrating Macrophage and Cancer Cell Membrane for Synergistic Chemodynamic/Immunotherapy/Photothermal Therapy of Breast Cancer.

Cell membrane-coated nanoplatforms for drug delivery have garnered significant attention due to their inherent cellular properties, such as immune evasion and homing abilities, making them a subject of widespread interest. The coating of mixed membranes from different cell types onto the surface of nanoparticles offers a way to harness natural cell functions, enhancing biocompatibility and improving therapeutic efficacy. In this study, we merged membranes from murine-derived 4T1 breast cancer cells with RAW264.7 (RAW) membranes, creating a hybrid biomimetic coating referred to as TRM. Subsequently, we fabricated hybrid TRM-coated Fe3O4 nanoparticles loaded with indocyanine green (ICG) and imiquimod (R837) for combination therapy in breast cancer. Comprehensive characterization of the RIFe@TRM nanoplatform revealed the inherent properties of both cell types. Compared to bare Fe3O4 nanoparticles, RIFe@TRM nanoparticles exhibited remarkable cell-specific self-recognition for 4T1 cells in vitro, leading to significantly prolonged circulation life span and enhanced in vivo targeting capabilities. Furthermore, the biomimetic RIFe@TRM nanoplatform induced tumor necrosis through the Fenton reaction and photothermal effects, while R837 facilitated enhanced uptake of tumor-associated antigens, further activating CD8+ cytotoxic T cells to strengthen antitumor immunotherapy. Hence, RIFe@TRM nanoplatform demonstrated outstanding synergy in chemodynamic/immunotherapy/photothermal therapies, displaying significant inhibition of breast tumor growth. In summary, this study presents a promising biomimetic nanoplatform for effective treatment of breast cancer.

Identification of potential therapeutic drugs targeting core genes for systemic lupus erythematosus (SLE) and coexisting COVID-19: Insights from bioinformatic analyses.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at risk during the COVID-19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID-19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. METHODS: The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein-protein interaction (PPI) network analysis, regulatory network construction, and gene-drug interaction construction. RESULTS: A total of 50 common DEGs were found between COVID-19 and SLE. Gene ontology (GO) functional annotation revealed that "immune response," "innate immune response," "plasma membrane," and "protein binding" were most enriched in. Additionally, the pathways that were enriched include "Th1 and Th2 cell differentiation." The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab-CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene-drug interaction. CONCLUSION: Four possible drugs that targeted two specific genes, which may be beneficial for COVID-19 patients with SLE.

Automated Fragmentation Quantum Mechanical Calculation of 15N and 13C Chemical Shifts in a Membrane Protein.

In this work, we developed an accurate and cost-effective automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method to calculate the chemical shifts of 15N and 13C of membrane proteins. The convergence of the AF-QM/MM method was tested using Krokinobacter eikastus rhodopsin 2 as a test case. When the distance threshold of the QM region is equal to or larger than 4.0 Å, the results of the AF-QM/MM calculations are close to convergence. In addition, the effects of selected density functionals, basis sets, and local chemical environment of target atoms on the chemical shift calculations were systematically investigated. Our results demonstrate that the predicted chemical shifts are more accurate when important environmental factors including cross-protomer interactions, lipid molecules, and solvent molecules are taken into consideration, especially for the 15N chemical shift prediction. Furthermore, with the presence of sodium ions in the environment, the chemical shift of residues, retinal, and retinal Schiff base are affected, which is consistent with the results of the solid-state nuclear magnetic resonance (NMR) experiment. Upon comparing the performance of various density functionals (namely, B3LYP, B3PW91, M06-2X, M06-L, mPW1PW91, OB95, and OPBE), the results show that mPW1PW91 is a suitable functional for the 15N and 13C chemical shift prediction of the membrane proteins. Meanwhile, we find that the improved accuracy of the 13Cß chemical shift calculations can be achieved by the employment of the triple-ζ basis set. However, the employment of the triple-ζ basis set does not improve the accuracy of the 15N and 13Cα chemical shift calculations nor does the addition of a diffuse function improve the overall prediction accuracy of the chemical shifts. Our study also underscores that the AF-QM/MM method has significant advantages in predicting the chemical shifts of key ligands and nonstandard residues in membrane proteins than most widely used empirical models; therefore, it could be an accurate computational tool for chemical shift calculations on various types of biological systems.

Fine-Tuning Electrolyte Concentration and Metal-Organic Framework Surface toward Actuating Fast Zn2+ Dehydration for Aqueous Zn-Ion Batteries.

Functional porous coating on zinc electrode is emerging as a powerful ionic sieve to suppress dendrite growth and side reactions, thereby improving highly reversible aqueous zinc ion batteries. However, the ultrafast charge rate is limited by the substantial cation transmission strongly associated with dehydration efficiency. Here, we unveil the entire dynamic process of solvated Zn2+ ions' continuous dehydration from electrolyte across the MOF-electrolyte interface into channels with the aid of molecular simulations, taking zeolitic imidazolate framework ZIF-7 as proof-of-concept. The moderate concentration of 2 M ZnSO4 electrolyte being advantageous over other concentrations possesses the homogeneous water-mediated ion pairing distribution, resulting in the lowest dehydration energy, which elucidates the molecular mechanism underlying such concentration adopted by numerous experimental studies. Furthermore, we show that modifying linkers on the ZIF-7 surface with hydrophilic groups such as -OH or -NH2 can weaken the solvation shell of Zn2+ ions to lower the dehydration free energy by approximately 1 eV, and may improve the electrical conductivity of MOF. These results shed light on the ions delivery mechanism and pave way to achieve long-term stable zinc anodes at high capacities through atomic-scale modification of functional porous materials.

Predictive factors and clinicopathological characteristics of outcome in poorly differentiated thyroid carcinoma: a single-institution study.

Objective: To elucidate the clinicopathological characteristics and prognostic factors of poorly differentiated thyroid carcinoma. Method: A total of 24912 thyroid carcinoma patients admitted to the First Medical Center of Chinese People's Liberation Army General Hospital from 2005 to 2020 were retrospectively reviewed. A total of 94 patients (39 males and 55 females, a male-female ratio of 1:1.4) fulfilled the selection criteria. Of these, 73 patients had undergone surgery. The clinical and pathological data were collected from each enrolled patient. Univariate and multivariate Cox regression analyses were performed to determine independent prognostic factors. All analyses were performed with the SPSS version 26.0 and R version 1.2.5033 in the R Studio environment. Results: The specimens included 20 cases of poorly differentiated thyroid carcinoma complicated with papillary thyroid carcinoma, 17 cases complicated with follicular thyroid carcinoma, 34 cases complicated with other pathological types and 23 with a separate entity. The patient demonstrated a large age span, median age was 57 years (range 8-85 years, average 55.20 ± 15.74 years). The survival time of the 94 cases was calculated, and the mean Overall survival time was 33 (range, 1-170) months, and the mean Recurrence-free survival time was 14 (range, 1-90) months. Recurrence-free mortality is related to the age at diagnosis, extrathyroidal extension and Associated thyroid cancer (p<0.05). In contrast, overall mortality is related to the age at diagnosis, sex, extrathyroidal extension, T stage (AJCC 8th), surgery and radiation (p<0.05). Conclusion: Middle-aged and elderly patients are still at high risk for poorly differentiated thyroid carcinoma. The pathologic results of poorly differentiated thyroid carcinoma are varied, and reasonable treatment has an important impact on the prognosis of poorly differentiated thyroid carcinoma.

Efficacy and safety of subcutaneous semaglutide in adults with overweight or obese: a subgroup meta-analysis of randomized controlled trials.

Introduction: Semaglutide shows significant performance on weight reduction in several clinical trials. However, it is not clear what kind of administration frequency or dosage will achieve better effects. This study aims to explore the different therapeutic effect of semaglutide on weight control under the diverse administration circumstances. Methods: The PubMed, Embase, Web of Science, Cochrane Library, and the Clinical Trials.gov were searched from inception until 6 June, 2022 to include randomized controlled trials evaluating the Efficacy and safety of subcutaneous semaglutide in overweight or obese adults. Random effects or fixed effects model was conducted based on the heterogeneity among trials. Subgroup analysis was performed to identify the detailed effects under different intervention situations. Results and discussion: Our study included 13 RCTs involving 5,838 participants with 3,794 ones in semaglutide group and 2,044 in placebo group. Semaglutide was associated with a significant reduction on weight loss related outcomes, including the absolute value of weight loss (WMD -8·97, 95% CI -10·73 to -7·21), percentage of weight loss (WMD -10·00, 95% CI -11·99 to -8·00), body mass index (WMD-3·19, 95% CI -4·02 to -2·37) and waist circumference (WMD -7·21,95% CI -8·87 to -5·56). Subgroup analyses illustrated participants with high weekly dosage, long-term treatment duration and severe baseline BMI (Class II obesity) had a more remarkably decreasing on the main outcomes of weight loss (P for interaction<0·05). Total adverse reactions occurred more frequently in the daily administration group than that in the weekly group (P for interaction =0·01). During the treatment, the incidence rate of hypoglycemia was higher in the group without lifestyle intervention compared with that with lifestyle intervention (P for interaction =0·04). Interpretation Subcutaneous semaglutide had significant benefits on weight loss with reasonable safety in overweight or obese adults. Moreover, additional benefits on cardiometabolic profiles were also seen. We recommended semaglutide treatment to be coupled with lifestyle interventions, and target dose of 2·0 mg or more subcutaneously once weekly. Clinicians can choose suitable treatment schemes based on diverse individual situations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337099, identifier PROSPERO (CRD42022337099).

Diagnostic value of a dynamic artificial intelligence ultrasonic intelligent auxiliary diagnosis system for benign and malignant thyroid nodules in patients with Hashimoto thyroiditis.

Background: A dynamic artificial intelligence (AI) ultrasonic intelligent assistant diagnosis system (dynamic AI) is a joint application of AI technology and medical imaging, which can conduct real-time synchronous dynamic analysis of nodules from multiple sectional views with different angles. This study explored the diagnostic value of dynamic AI for benign and malignant thyroid nodules in patients with Hashimoto thyroiditis (HT) and its significance in guiding surgical treatment strategies. Methods: Data of 487 patients (154 with and 333 without HT) with 829 thyroid nodules who underwent surgery were collected. Differentiation of benign and malignant nodules was performed using dynamic AI, and diagnostic effects (specificity, sensitivity, negative predictive value, positive predictive value, accuracy, misdiagnosis rate and missed diagnosis rate) was assessed. Differences in diagnostic efficacy were compared among AI, preoperative ultrasound based on the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS), and fine needle aspiration cytology (FNAC) diagnoses. Results: The accuracy, specificity and sensitivity of dynamic AI reached 88.06%, 80.19%, and 90.68%, respectively; besides, there was consistency with postoperative pathological consequences (κ=0.690; P<0.001). The diagnostic efficacy of dynamic AI was equivalent between patients with and without HT, and there were no significant differences in sensitivity, specificity, accuracy, positive predictive value, negative predictive value, missed diagnosis rate, and misdiagnosis rate. In patients with HT, dynamic AI had significantly higher specificity and a lower misdiagnosis rate than did preoperative ultrasound based on the ACR TI-RADS (P<0.05). Compared with FNAC diagnosis, dynamic AI had a significantly higher sensitivity and a lower missed diagnosis rate (P<0.05). Conclusions: Dynamic AI possessed an elevated diagnostic worth of malignant and benign thyroid nodules in patients with HT, which can provide a new method and valuable information for the diagnosis and development of management strategy of patients.

Quantifying the air quality impact of ship emissions in China's Bohai Bay.

Bohai Bay, as a significant economic bay area in China, has experienced considerable ecological consequences during its rapid economic development. One of the major environmental challenges is the emission of air pollutants from ships, which has had a severe impact on regional air quality and the health of residents. To assess the influence of pollutants on the air quality around the Bohai Bay area, a Weather Research and Forecasting and Community Multiscale Air Quality (WRF-CMAQ) model was established using a 9 km × 9 km high-resolution ship emission gridded inventory from 2018. The WRF-CMAQ model was employed to compare two scenarios: vessel emissions and non-vessel emissions, in order to evaluate the impact of ship emissions. By analyzing the pollutant concentrations in Bohai Bay and the degree of change in pollutant concentration in six cities under these two scenarios, significant differences were observed. Furthermore, a comparison of the hourly concentration contributions of ship emissions between port cities and inland cities within the same region revealed that inland cities were less affected by ship emissions. The main contributing factors to this disparity were identified as wind direction and wind speed.

Directing Highly a-Axis-Oriented ZSM-5 Nanosheets with Pre-estimated Bifunctional Imidazole Cations.

An MFI-topology nanosheet zeolite with a highly a-axis-oriented structure has rarely been reported but with a great potential for industrial applications. Theoretical calculations on the interaction energies between the MFI skeleton and ionic liquid molecules indicated the possibility of preferential crystal growth along a specific direction, according to which highly a-oriented ZSM-5 nanosheets were synthesized from commercially available 1-(2-hydroxyethyl)-3-methylimidazolium and layered silicate sources. The imidazolium molecules directed the structure formation and meanwhile acted as zeolite growth modifiers to restrict the crystal growth perpendicular to the MFI bc plane, which induced unique a-axis-orientated thin sheets with ∼12 nm thickness. The a-oriented ZSM-5 exhibited more competitive propylene selectivity and longer lifetime than bulky crystals in methanol-to-propylene (MTP) reaction. This research would provide a versatile protocol for the rational design and synthesis of shape-selective zeolite catalysts with promising applications.

A real-world data analysis of topotecan in the FDA Adverse Event Reporting System (FAERS) database.

OBJECTIVES: The objective of this study was to monitor and identify adverse events (AEs) associated with topotecan, a medication used for the treatment of solid tumors, in order to improve patient safety and guide medication usage. METHODS: To assess the disproportionality of topotecan-related AEs in real-world data, four algorithms (ROR, PRR, BCPNN, and EBGM) were employed as measures to detect signals of topotecan-associated AEs. RESULTS: A statistical analysis was conducted using data from the FAERS database, encompassing 9,511,161 case reports from 2004Q1 to 2021Q4. Among these reports, 1,896 were identified as primary suspected (PS) AEs related to topotecan, and 155 topotecan-related adverse drug reactions (ADRs) at the preferred terms (PTs) level were selected. The occurrence of topotecan-induced ADRs was analyzed across 23 organ systems. The analysis revealed several expected ADRs, such as anemia, nausea, and vomiting, which were consistent with the drug labels. Additionally, unexpected significant ADRs associated with eye disorders at the system organ class (SOC) level were identified, indicating potential adverse effects not currently mentioned in the drug instructions. CONCLUSION: This study identified new and unexpected signals of adverse drug reactions (ADRs) related to topotecan, providing valuable insights into the relationship between ADRs and topotecan usage. The findings highlight the importance of ongoing monitoring and surveillance to detect and manage AEs effectively, ultimately improving patient safety during topotecan treatment.

Layered Zeolite for Assembly of Two-Dimensional Separation Membranes for Hydrogen Purification.

Membrane separation is an energy-efficient and environmentally friendly process. Two-dimensional (2D) molecular sieving membranes featuring unique nanopores and low transport resistance have the potential to achieve highly permeable and selective mixture separation with low energy consumption. High-aspect-ratio zeolite nanosheets with intrinsic molecular-sieving pores perpendicular to the layers are desirable building blocks for fabricating high-performance 2D zeolite membrane. However, a wider application of 2D zeolitic membranes is restricted by the limited number of recognized zeolite nanosheets. Herein, we report a swollen layered zeolite, ECNU-28, with SZR topology and eight-member ring (8-MR, 3.0 Å×4.8 Å) pores normal to the nanosheets. It can be easily exfoliated to construct 2D membrane, which shows a high hydrogen selectivity up to 130 from natural gas and is promising for hydrogen purification and greenhouse gas capture.

Precise diagnosis and successful surgical intervention of the median arcuate ligament syndrome: A case report.

INTRODUCTION AND IMPORTANCE: The median arcuate ligament syndrome (MALS) is a rare disorder that produces a spectrum of symptoms due to compression of the arcuate ligament, clinically manifested primarily by abdominal pain, nausea, vomiting, and weight loss. The mechanism of these symptoms has not yet been revealed, and the current treatment methods are still somewhat controversial. CASE PRESENTATION: We present a 54-year-old woman who presented with intermittent epigastric pain for nine months. During the onset, she lost 7.5 kg. After routine examinations in a nearby hospital, no abnormality was found. She was referred to us. CTA showed compression of the celiac artery. Further selective celiac angiography at the end of inspiration and expiration confirmed MALS. After consultation with the patient, the decision to have a laparotomy was made. The celiac artery was completely skeletonized, and external compression on the artery was released. Postoperative symptoms improved significantly. One-year follow-up after the operation, she had a weight gain of 4.8 kg and was satisfied with the surgical results. CLINICAL DISCUSSION: The manifestations of MALS are varied and challenging. Our patient presented with weight loss and intermittent abdominal pain. The mutual confirmation of multiple investigations can provide a more comprehensive overview of celiac artery compression. We confirmed using ultrasonography, CT angiography, and selective digital subtraction angiography in this case. The celiac artery compression was relieved after open surgery. Our patient's symptoms improved significantly after surgery. We hope our treatment method can provide a reference for MALS diagnosis and treatment. CONCLUSION: It is challenging to diagnose MALS. Cross-confirmation of multiple examinations can provide a more comprehensive view of celiac compression. Surgical decompression of the celiac artery (open or laparoscopic surgery) may be an effective therapy for MALS, especially in centers with experience.

Screening of Therapeutic Targets for Pancreatic Cancer by Bioinformatics Methods.

Pancreatic cancer (PC) has the lowest survival rate and the highest mortality rate among all cancers due to lack of effective treatments. The objective of the current study was to identify potential therapeutic targets in PC. Three transcriptome datasets, namely GSE62452, GSE46234, and GSE101448, were analyzed for differentially expressed genes (DEGs) between cancer and normal samples. Several bioinformatics methods, including functional analysis, pathway enrichment, hub genes, and drugs were used to screen therapeutic targets for PC. Fisher's exact test was used to analyze functional enrichments. To screen DEGs, the paired t-test was employed. The statistical significance was considered at p <0.05. Overall, 60 DEGs were detected. Functional enrichment analysis revealed enrichment of the DEGs in "multicellular organismal process", "metabolic process", "cell communication", and "enzyme regulator activity". Pathway analysis demonstrated that the DEGs were primarily related to "Glycolipid metabolism", "ECM-receptor interaction", and "pathways in cancer". Five hub genes were examined using the protein-protein interaction (PPI) network. Among these hub genes, 10 known drugs targeted to the CPA1 gene and CLPS gene were found. Overall, CPA1 and CLPS genes, as well as candidate drugs, may be useful for PC in the future.

Concurrence of multiple aneurysms, extreme coiling of the extracranial internal carotid artery and ipsilateral persistent primitive hypoglossal artery: A case report and literature review.

Background: The primitive hypoglossal artery (PHA) is an anastomotic vessel of the carotid-basilar artery system that is prevalent only transiently during the embryonic period. Persistent primitive hypoglossal artery (PPHA) is a rare vessel variation in which PHA exists persistently in adulthood and occurs in approximately 0.02-0.1% of the population. Tortuosity of the extracranial internal carotid artery (ICA) is relatively common, impacting 10-43% of the population, and is caused by either congenital or acquired factors. It is still unknown whether PPHA and tortuosity of extracranial ICA are associated. Here, we present a case report of the concurrence of three types of pathologies of the carotid artery: extreme coiling of the extracranial internal carotid artery, multiple aneurysms and persistent primitive hypoglossal artery. Case description: A 66-year-old woman suffered intermittent headaches, dizziness and numbness of the right eyelid for 5 years. Magnetic resonance angiography performed in a local hospital reported an aneurysm of the posterior communicating artery segment of the left ICA and a left PPHA. Digital subtraction angiography conducted after admission showed a PPHA originating from the left cervical ICA and an extremely coiling segment of the ICA distal to the beginning of PPHA. Except for the aneurysm of the posterior communicating artery segment of the left ICA, multiple aneurysms were found at the coiling segment of the ICA. Conclusion: To the best of our knowledge, this is the first report of PPHA accompanied by an adjacent, extremely coiling ICA. There are no reports of similar tortuous ICAs to this extent or at this position. Including aneurysms, three types of pathologies suggest their congenital origin, and a review of the literature infers the probable association of these lesions.