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Purpose: To evaluate and validate CT-based models using pre- and posttreatment deep learning radiomics features and hematological biomarkers for assessing esophageal squamous cell carcinoma (ESCC) pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Material and methods: This retrospective study recruited patients with biopsy-proven ESCC who underwent nCRT from two Chinese hospitals between May 2017 and May 2022, divided into a training set (hospital I, 111 cases), an internal validation set (hospital I, 47 cases), and an external validation set (hospital II, 33 cases). We used minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) as feature selection methods and three classifiers as model construction methods. The assessment of models was performed using area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA). Results: A total 190 patients were included in our study (60.8 ± 7.08 years, 133 men), and seventy-seven of them (40.5 %) achieved pCR. The logistic regression (LR)-based combined model incorporating neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, albumin, and radscores performed well both in the internal and external validation sets with AUCs of 0.875 and 0.857 (95 % CI, 0.776–0.964; 0.731–0.984, P

This study aimed to explore the clinical efficacy of ultrasound-guided interventional therapy in patients with benign ovarian cysts through meta-analysis. A literature search was performed on PubMed, Web of Science, Embase, CNKI, and WanFang databases to obtain clinical randomized controlled trials on ultrasound-guided interventional therapy for benign ovarian cysts published between 2010 and 2022. A total of 1395 studies were initially retrieved, and finally 12 studies were included for meta-analysis. The results showed that the observation group (ultrasound-guided interventional therapy) had higher treatment effective rate than the control group (conventional laparotomy or laparoscopic cyst resection), but the incidence of adverse reactions was markedly lower. Additionally, the length of hospital stay, intraoperative blood loss, and operation time showed significant lower levels in the observation group. In terms of ovarian function, postoperative luteinizing hormone and follicle-stimulating hormone levels in the observation group were lower than the control group, while oestradiol levels were higher. In conclusion, compared with conventional surgical treatment, ultrasound-guided interventional therapy can significantly improve the clinical effective rate, shorten the hospital stay and reduce intraoperative blood loss. Such therapy can protect ovarian reserve, with high value of clinical promotion.IMPACT STATEMENT What is already known on this subject? Main surgical methods for ovarian cysts consist of laparotomy, laparoscopic surgery, and interventional therapy. What the results of this study add? With the advancement of surgical techniques and instruments, many minimally invasive surgeries have been applied to treat ovarian cysts with good clinical results. However, there is no exact evidence to prove its clinical efficacy. Given the lack in this field, we conducted a meta-analysis of all clinical studies of ultrasound-guided interventional therapy for ovarian cysts to evaluate its efficacy and safety. What the implications are of these findings for clinical practice and/or further research? Compared with conventional laparotomic or laparoscopic cyst resection, ultrasound-guided interventional therapy for ovarian cysts significantly improves the treatment effectiveness, shortens the hospital stay and reduces intraoperative blood loss. This therapy with good clinical efficacy also has advantages of small wound, rapid recovery and less adverse reactions, and can protect ovarian reserve. This safe and effective surgical method for ovarian cysts is worth promoting clinically.

In advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have an excellent and long-lasting therapeutic response; however, virtually all patients eventually develop drug resistance and experience disease progression. The use of immunotherapy after EGFR-TKIs may be a successful therapeutic option for individuals who are resistant to them. It is still unclear if EGFR-TKIs can be administered again after immunotherapy has failed. We describe a case of a 37-year-old woman who was found to have T4N3M1a stage IVa lung adenocarcinoma. Amplification refractory mutation system PCR (ARMS-PCR) genetic testing suggested EGFR exon 19 deletion. The patient was initially treated with a regimen of icotinib (125 mg tid) combined with anlotinib (8 mg qd d1-d14) with an optimal efficacy rating of partial response (PR) and was granted a PFS of 7 months. In second-line treatment, the patient received three cycles of a KN046 (KN046 is a bispecific antibody inhibitor of PD-L1 and CTLA-4) 295 mg d1, pemetrexed 800 mg d1, plus carboplatin 750 mg d1 regimen, with an optimal efficacy rating of stable disease (SD) on CT. The third-line therapy was chosen to be afatinib with docetaxel, and the patient was evaluated for PR on CT. Up to 15 August 2022, the patient had a progression free survival (PFS) of 14 months. The successful treatment of this patient is a reminder that EGFR-TKI rechallenge in EGFR exon 19 deletion patients with EGFR-TKI resistance, in which immunotherapy has failed, may be effective.

Abstract Background Immature ovarian teratoma is one of the three common malignant ovarian germ cell tumors. However, immature ovarian teratoma in pregnancy is very rare. Due to the rare occurrence, there is little evidence regarding its diagnosis, optimal management, and prognosis. Hence, we present a case of immature teratoma diagnosed during pregnancy, and analyze its clinicopathological features, management and prognosis. Case presentation A 28-year-old woman underwent a sonographic examination revealed no abnormality in the bilateral adnexal area before 29 weeks gestational age (WGA). At 29 WGA, ultrasound demonstrated a 9.7 × 8.5 × 6.4 cm complex structure in the left adnexal area. At 30 WGA, repeated ultrasound revealed rapid growth of tumor mass, measuring 25.0 × 15.0 × 13.7 cm. An elective cesarean section combined with exploratory laparotomy was performed at 33 WGA. Intraoperative frozen pathological examination suggested left ovarian immature teratoma. Then, she underwent a complete staging surgery. Subsequently, the patient received 4 cycles of bleomycin-etoposide-cisplatin (BEP) chemotherapy. After 18 months of follow-up, there is no sign of tumor recurrence till now. Conclusions This case report suggests that the benefits and risks of timely treatment for patients and fetuses should be fully assessed by a multidisciplinary team. The early diagnosis, the timing of surgery and chemotherapy, the choice of chemotherapy for BEP will determine the prognosis. Surgery and combination chemotherapy with BEP play an important role in the treatment of immature teratomas in pregnancy, and could gain successful and satisfactory outcomes for mother and fetus.

Objective Peri-implantitis is characterized by peri-implant mucositis and alveolar bone resorption. This study investigated cholecystokinin ( CCK ) expression and the mechanism underlying its involvement in peri-implantitis. Methods mRNA sequencing was performed using the Gene Expression Omnibus database GSE106090. Human bone marrow mesenchymal stem cells (hBMSCs) were pretreated with various concentrations of CCK (0, 10, 30, or 100 nM) for 1 hour before induction in osteogenic differentiation medium for 2 weeks. Alkaline phosphatase (ALP) activity was determined, and the cells were stained with alizarin red. The expression levels of TNFα and the osteogenic markers ALP , RUNX2 , and OCN were measured using quantitative real-time PCR. TNFα, phosphorylated P65, and total P65 levels were determined by western blot. Results Compared with healthy individuals, 262 and 215 genes were up- and down-regulated, respectively, in the periodontal tissues of patients with peri-implantitis. CCK expression was significantly upregulated in patients with peri-implantitis. CCK reduced ALP activity, osteogenic differentiation, and levels of the osteogenic markers ALP , RUNX2 , and OCN . Moreover, CCK promoted levels of TNFα and phosphorylated P65, which is a marker of activation for the NF-κB inflammatory pathway. Conclusions CCK regulates osteogenic differentiation through the TNFα/NF-κB axis in peri-implantitis.

Background Acute myocardial infarctions are increasingly common among young adults. We investigated sex and racial differences in the evaluation of chest pain (CP) among young adults presenting to the emergency department. Methods and Results Emergency department visits for adults aged 18 to 55 years presenting with CP were identified in the National Hospital Ambulatory Medical Care Survey 2014 to 2018, which uses stratified sampling to produce national estimates. We evaluated associations between sex, race, and CP management before and after multivariable adjustment. We identified 4152 records representing 29 730 145 visits for CP among young adults. Women were less likely than men to be triaged as emergent (19.1% versus 23.3%, respectively, P

In an effort to deepen the understanding of nature of interactions between CuCl-based ionic liquids and thiophene, the electronic and topological properties of interactions between 1-butyl-3-methylimidazolium ([BMIM]+[Cu2Cl3]−) and thiophene (TS) have been investigated by the density functional theory. The occurrence of interactions caused by resonance effects between virtual orbitals of Cu and virtual orbitals of thiophene has been corroborated at the molecular level.

In the title compound, {[Co2(C16H6O8)(C12H8N2)(H2O)2]·H2O}n, one CoII ion has a {CoN2O4} distorted octahedral environment defined by two N atoms of one 1,10-phenanthroline (phen) ligand, three O atoms of the carboxylate groups of three biphenyl-3,3′,4,4′-tetracarboxylate (BPTC) ligands, one of which is bidentate, and one O atom from one coordinated water molecule. The other CoII atom is surrounded by six O atoms from four different BPTC ligands and one coordinated water molecule. Each BPTC ligand forms eight coordination bonds with seven CoII atoms, leading to a layer structure along the ac plane. Uncoordinated water molecules occupy the space between the layers, and interact via interlayer O—H...O hydrogen bonds along the b axis, generating a three-dimensional supramolecular network.

Single-cell RNA sequencing (scRNA-seq) data, susceptible to noise arising from biological variability and technical errors, can distort gene expression analysis and impact cell similarity assessments, particularly in heterogeneous populations. Current methods, including deep learning approaches, often struggle to accurately characterize cell relationships due to this inherent noise. To address these challenges, we introduce scAMF (Single-cell Analysis via Manifold Fitting), a framework designed to enhance clustering accuracy and data visualization in scRNA-seq studies. At the heart of scAMF lies the manifold fitting module, which effectively denoises scRNA-seq data by unfolding their distribution in the ambient space. This unfolding aligns the gene expression vector of each cell more closely with its underlying structure, bringing it spatially closer to other cells of the same cell type. To comprehensively assess the impact of scAMF, we compile a collection of 25 publicly available scRNA-seq datasets spanning various sequencing platforms, species, and organ types, forming an extensive RNA data bank. In our comparative studies, benchmarking scAMF against existing scRNA-seq analysis algorithms in this data bank, we consistently observe that scAMF outperforms in terms of clustering efficiency and data visualization clarity. Further experimental analysis reveals that this enhanced performance stems from scAMF's ability to improve the spatial distribution of the data and capture class-consistent neighborhoods. These findings underscore the promising application potential of manifold fitting as a tool in scRNA-seq analysis, signaling a significant enhancement in the precision and reliability of data interpretation in this critical field of study. [ABSTRACT FROM AUTHOR]

Abstract Background Hypoxia is a characteristic of solid tumors, but whether significant hypoxia exists in the hepatocellular carcinoma remains unclear. This animal study aims to explore the value of dynamic contrast-enhanced ultrasound (CEUS) quantitative parameters to evaluate the oxygen status in two rat hepatoma models. Materials and methods N1S1 and McA-RH7777 S-D rat orthotopic hepatoma models were established. Once the tumors reached a diameter of 10–15 mm, CEUS and oxygen partial pressure (pO2) polarography were performed. Immunohistochemical staining for HIF-1α and pimonidazole was conducted after euthanizing the rats. Correlation between quantitative CEUS parameters, pO2, and the immunohistochemical integrated optical density (IOD) was analyzed to assess the predictive ability of CEUS quantitative parameters for the tissue oxygen environment. Result Eleven N1S1 models and ten McA-RH7777 models were established successfully. There was no significant difference in pO2 (35.5 mmHg vs 32.2 mmHg, P = 0.917), IOD of HIF-1α (13.4 vs 20.0, P = 0.159) and pimonidazole (0.70 vs 1.30, P = 0.926) between the tumor and the peritumoral liver tissue. The pO2 values were correlated with CEUS quantitative parameters including mean time-intensity curves (mTIC) (P = 0.003), peak intensity (PKI) (P = 0.010), area under the curve (AUC) (P = 0.009), area under the wash-in curve (WiAUC) (P = 0.006), and arrival time (AT) (P = 0.033). The IOD of HIF-1α correlated with AUC (P = 0.022), WiAUC (P = 0.009), ascending slope (AS) (P = 0.044), and falling time (FT) (P = 0.009). Multiple linear regression indicated that the “short AT” was an independent protective factor for hypoxia (β = -2.347, 95% CI: -4.948, -0.394, P = 0.022), and CEUS had the ability to predict the tumor pO2 (P = 0.003). Conclusion No evidence of significant hypoxia was identified in two rat orthotopic hepatoma models. Quantitative CEUS parameters correlated with the oxygen status of the tumor, which could be utilized to predict the tumor tissue pO2.

Abstract Objectives To investigate the value of vascular morphology on high frame rate contrast-enhanced ultrasound (H-CEUS) and CEUS Li-RADS in predicting microvascular invasion (MVI), Ki-67 expression and recurrence of hepatocellular carcinoma (HCC). Methods This retrospective study enrolled 78 patients with single HCC diagnosed by postoperative pathology between January 1, 2021, and June 30, 2022. All patients underwent ultrasound and H-CEUS examination before operation. H-CEUS image features and CEUS Li-RADS were compared in different MVI status and Ki-67 level. Multiple logistic regression analysis was performed to select independent variables for MVI. Differences in recurrence among different H-CEUS image features, MVI status and Ki-67 level were further analyzed. Results Tumor shape, vascular morphology, LR-M category, necrosis and AFP level were different between the MVI-positive group and MVI-negative group (p

Objective To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea.Methods Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated.Results A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73).Conclusion For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.

Abstract Background Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. Methods In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. Results Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. Conclusions The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair. Graphical Abstract

Abstract Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body’s in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.