Comparison of gemcitabine/carboplat in versus paclitaxel/cisplatin for the management of non small cell lung cancer

Purpose: To determine the comparative efficacy and toxicity of gemcitabine/carboplatin and paclitaxel/cisplatin in patients with completely resected stage IIa - IIIa non-small cell lung cancer (NSCLC). Methods: Sixty eligible NSCLC patients treated in Funan County People's Hospital were enrolled and assigned to two groups by randomization (n = 30 each). One group (CG group) received the combination of gemcitabine and carboplatin, while the second group (CP group) received a combination of cisplatin and paclitaxel. Efficacy was assessed based on 2-year progression-free survival, while adverse reactions were recorded to assess the toxicity of the chemotherapy treatments. Results: No marked difference was found in the 2-year relapse-free survival in the two groups with similar clinical baseline characteristics after follow-up (60 % in CG group vs. 56.67 % in CP group, p = 0.826). Specifically, no significant difference was found between the two groups with regard to incidence of local metastases, distant metastases, or brain tissue metastases within 2 years, and there were no treatment-related deaths. CG group was more likely to develop leukopenia (93.33 % vs. 63.33 % for CP group, p = 0.04), but no significant difference was observed for other adverse effects such as anemia, vomiting, and nausea. Conclusion: This study shows that adjuvant treatment using carboplatin and gemcitabine produces the same therapeutic efficacy as cisplatin and paclitaxel, but exhibits higher toxicity levels than the latter

Reinforcement Learning Based Gasoline Blending Optimization: Achieving More Efficient Nonlinear Online Blending of Fuels

The online optimization of gasoline blending benefits refinery economies. However, the nonlinear blending mechanism, the oil property fluctuations, and the blending model mismatch bring difficulties to the optimization. To solve the above issues, this paper proposes a novel online optimization method based on deep reinforcement learning algorithm (DRL). The Markov decision process (MDP) expression are given considering a practical gasoline blending system. Then, the environment simulator of gasoline blending process is established based on the MDP expression and the one-year measurement data of a real-world refinery. The soft actor-critic (SAC) DRL algorithm is applied to improve the DRL agent policy by using the data obtained from the interaction between DRL agent and environment simulator. Compared with a traditional method, the proposed method has better economic performance. Meanwhile, it is more robust under property fluctuations and component oil switching. Furthermore, the proposed method maintains performance by automatically adapting to system drift.Comment: 30 pages,13 figure

A tumor-like renal arteriovenous malformation on 18F-PSMA-1007 PET/CT: a case report

BackgroundRenal arteriovenous malformations (rAVMs) are congenital abnormal pathways between renal arteries and veins that are rare in the general population. It is often misdiagnosed as malignant renal tumors with abundant blood supply, and the definitive diagnosis primarily relies on angiography. Multimodality imaging, including contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT plays an important role in the differential diagnosis of renal space-occupying lesions.Case presentationA 56-year-old man presented with abdominal distension, loss of appetite, and back pain without obvious cause 2 years ago, without nausea vomiting, or frequent urination. Gastroscopy and colonoscopy showed multiple polyps in the duodenum and colon. Abdomen contrast-enhanced CT revealed a mass of 1.6 × 1.4 cm in the left kidney, which was considered to be a malignant tumor. PET/CT was performed for further diagnosis; the 18F-fluorodesoxyglucose (18F-FDG) PET/CT scan showed mild uptake in the left renal mass, while no uptake of 18F- prostate-specific membrane antigen (PSMA) was observed. Following a multidisciplinary discussion, the possibility of renal AVMs was considered and subsequently confirmed by renal angiography as the diagnosis. Then, selective segmental renal artery embolization was performed for treatment.ConclusionRenal AVMs are extremely rare in clinical practice. Due to limited research on the application of 18F-FDG and 18F-PSMA PET/CT to renal AVMs, its role remains largely unexplored. With the increasing popularity of PET/CT imaging, comprehensive imaging of the disease has become indispensable. We report the first case of PSMA PET/CT imaging in renal AVMs, and when PSMA expression is absent in a renal mass, the possibility of renal AVMs should be considered

Automatic nodule identification and differentiation in ultrasound videos to facilitate per-nodule examination

Ultrasound is a vital diagnostic technique in health screening, with the advantages of non-invasive, cost-effective, and radiation free, and therefore is widely applied in the diagnosis of nodules. However, it relies heavily on the expertise and clinical experience of the sonographer. In ultrasound images, a single nodule might present heterogeneous appearances in different cross-sectional views which makes it hard to perform per-nodule examination. Sonographers usually discriminate different nodules by examining the nodule features and the surrounding structures like gland and duct, which is cumbersome and time-consuming. To address this problem, we collected hundreds of breast ultrasound videos and built a nodule reidentification system that consists of two parts: an extractor based on the deep learning model that can extract feature vectors from the input video clips and a real-time clustering algorithm that automatically groups feature vectors by nodules. The system obtains satisfactory results and exhibits the capability to differentiate ultrasound videos. As far as we know, it's the first attempt to apply re-identification technique in the ultrasonic field

Functional and structural analysis of a novel splice site HMBS variant in a Chinese AIP patient

Background: Acute intermittent porphyria (AIP) is a rare metabolic disorder that results from mutations in the gene encoding hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP follows an autosomal dominant inheritance pattern, but most carriers are asymptomatic. The clinical manifestations of AIP include acute attacks of abdominal pain and neuropsychiatric disturbances. The pathogenicity of novel HMBS variants identified in Chinese patients has not been well established.Objective: The article aims to identify the pathogenic mutation in an AIP patient and prove its pathogenicity through in vitro experiments.Methods: A 22-year-old female diagnosed with AIP participated in the study. Variant screening of her HMBS gene was carried out through Sanger sequencing. To ascertain the consequences of the newly discovered variant, we conducted in vitro experimentation targeting HMBS gene expression and enzymatic function. Additionally, protein structure analysis was performed. Cycloheximide treatment and UPF1-specific siRNA knockdown were employed to assess the impact of the mutation on the mechanism of non-sense-mediated mRNA decay (NMD).Results: A novel splice site variant in the HMBS gene (c.648_651+1delCCAGG) was detected in the patient, which caused aberrant mRNA splicing. In vitro experiments demonstrated that this variant significantly decreased the expression of HMBS. Further investigation confirmed that this decrease was due to NMD. Additionally, structural analysis indicated that this variant would destabilize the HMBS protein and impair its catalytic activity. To gain a comprehensive understanding of HMBS mutations in the context of AIP, we conducted a literature search on PubMed using the keywords ‘HMBS’ and ‘Acute intermittent porphyria’ from 2013 to 2023. This search yielded 19 clinical case reports written in English, which collectively described 220 HMBS gene mutations worldwide.Conclusion: The study identified and proved the pathogenicity of a novel splice site HMBS variant for the first time. Our results elucidated the pathological mechanism by which this mutation causes AIP through reducing HMBS expression and activity. These findings provide theoretical guidance for the diagnosis, treatment and genetic counseling of AIP patients

Simple Cholecystectomy Is Adequate for Patients With T1b Gallbladder Adenocarcinoma < 1 cm in Diameter

Purpose: Consensus-based clinical guidelines recommend that simple cholecystectomy (SC) is adequate for T1a gallbladder adenocarcinoma (GBA), but extended cholecystectomy (EC), SC plus lymphatic dissection, should be considered for T1b and more advanced GBA. Whether lymphatic dissection is necessary for the treatment of T1b GBA remains controversial. This study attempts to better define the current criteria for local treatment of T1b GBA, by examining the relationship between lymph node (LN) metastasis and tumor size in such patients.Patients and methods: Clinical data from patients with T1b GBA receiving curative surgical treatment between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Baseline characteristics for the entire cohort were described, and overall survival (OS) and cancer-specific survival (CSS) were analyzed with the Kaplan–Meier method.Results: In total, 277 patients were enrolled for further analysis; 127 underwent lymphadenectomy. Among them, 23 patients had tumors &lt;1 cm in diameter, none of which had LN metastasis; 104 patients had tumors ≥1 cm, 15 of which had positive LNs. In the group with tumor size &lt;1 cm, there was no significant survival difference between treatment with SC or EC (P = 0.694). A clinical benefit was observed in T1b GBA patients with a tumor size ≥1 cm receiving EC vs. those receiving SC (P = 0.012).Conclusion: SC was adequate for treatment of T1b GBA &lt; 1 cm in diameter. This evidence may be included as part of current guidelines

Structural Insights Into Ligand Recognition and Selectivity of Somatostatin Receptors

Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of Gi1-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of Gi1-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs

Atrial Fibrillation Follow-up Investigation to Recover Memory and Learning Trial (AFFIRMING): Rationale and Design of a Multi-center, Double-blind, Randomized Controlled Trial

Background: People with atrial fibrillation (AF) have elevated risk of developing cognitive impairment. At present, there is a dearth of randomized controlled trials investigating cognitive impairment management in patients with AF. The Atrial Fibrillation Follow-up Investigation to Recover Memory and learning (AFFIRMING) study is aimed at evaluating the potential for computerized cognitive training to improve cognitive function in patients with AF. Methods: The study is a multi-center, double-blind, randomized controlled study using a 1:1 parallel design. A total of 200 patients with AF and mild cognitive decline without dementia are planned to be recruited. The intervention group will use the adaptive training software with changes in difficulty, whereas the positive control group will use basic training software with minimal or no variation in difficulty level. At the end of 12 weeks, the participants will be unblinded, and the positive control group will stop training. The intervention group will be rerandomized 1:1 to stop training or continue training. All participants will be followed up until 24 weeks. The primary endpoint is the proportion of the improvement of the global cognitive function at week 12 compared with baseline, using the Basic Cognitive Ability Test (BCAT)