DCRELM: dual correlation reduction network-based extreme learning machine for single-cell RNA-seq data clustering.

Single-cell ribonucleic acid sequencing (scRNA-seq) is a high-throughput genomic technique that is utilized to investigate single-cell transcriptomes. Cluster analysis can effectively reveal the heterogeneity and diversity of cells in scRNA-seq data, but existing clustering algorithms struggle with the inherent high dimensionality, noise, and sparsity of scRNA-seq data. To overcome these limitations, we propose a clustering algorithm: the Dual Correlation Reduction network-based Extreme Learning Machine (DCRELM). First, DCRELM obtains the low-dimensional and dense result features of scRNA-seq data in an extreme learning machine (ELM) random mapping space. Second, the ELM graph distortion module is employed to obtain a dual view of the resulting features, effectively enhancing their robustness. Third, the autoencoder fusion module is employed to learn the attributes and structural information of the resulting features, and merge these two types of information to generate consistent latent representations of these features. Fourth, the dual information reduction network is used to filter the redundant information and noise in the dual consistent latent representations. Last, a triplet self-supervised learning mechanism is utilized to further improve the clustering performance. Extensive experiments show that the DCRELM performs well in terms of clustering performance and robustness. The code is available at https://github.com/gaoqingyun-lucky/awesome-DCRELM .

Postoperative hypoxemia for patients undergoing Stanford type A aortic dissection.

Clinically, it is widely recognized that surgical treatment is the preferred and reliable option for Stanford type A aortic dissection. Stanford type A aortic dissection is an emergent and serious cardiovascular disease characterized with an acute onset, poor prognosis, and high mortality. However, the incidences of postoperative complications are relatively higher due to the complexity of the disease and its intricate procedure. It has been considered that hypoxemia, one of the most common postoperative complications, plays an important role in having a worse clinical prognosis. Therefore, the effective intervention of postoperative hypoxemia is significant for the improved prognosis of patients with Stanford type A aortic dissection.

Pathological characteristics and tumour immune microenvironment of lung malignancies with RET rearrangement.

BACKGROUND: For patients with lung malignancies with RET rearrangement, the efficacy of immune checkpoint inhibitors is limited. The characteristics of the tumour immune microenvironment (TIME) and molecular pathological features of these patients have not been well elucidated. We aimed to investigate their clinical outcomes and explore characteristics of TIME, using multiplex immunohistochemistry technology (mIHC). PATIENTS AND METHODS: The pathology and TIME characteristics of 29 patients with lung malignancies with RET rearrangement were retrospectively analysed, and their relationships with clinical efficacy and prognosis were investigated. Gene detection relied on high-throughput sequencing, and TIME detection was based on mIHC. RESULTS: Of 29 patients, 25(86%) had adenocarcinoma, and the acinar type accounted for the greatest percentage of patients, followed by the solid type, regardless of whether the disease was early or locally advanced and metastatic. In addition, we report a novel KIF5B-RET(k24:R8) rearrangement in pulmonary sarcoma. The density of CD8+ T cells in tumour stroma in early-stage patients was significantly higher than that in locally advanced and metastatic patients (P = 0.014). The proportion of M2 macrophages in tumour stroma was significantly higher than that in tumour parenchyma (P = 0.046). Although the difference was not statistically significant (P = 0.098), patients positive for M2 macrophage infiltration into the tumour parenchyma (≥5%) may have a better prognosis. Seven patients received immunotherapy and disease control rate was 85.7%. CONCLUSIONS: A novel KIF5B-RET rearrangement variant in pulmonary sarcoma shows similar TIME characteristics to lung cancer. amongst patients with lung malignancies with RET rearrangement, patients with M2 macrophage infiltration into the tumour parenchyma may have a better prognosis, but further studies with larger cohorts are needed.

Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study.

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.

[Advances in the Treatment of RET Fusion-positive Advanced Non-small Cell Lung Cancer].

Rearranged during transfection (RET) fusions are found in 0.7% to 2% of non-small cell lung cancer (NSCLC). Fusions between RET gene and other domains represent the distinct biological and clinicopathological subtypes of NSCLC. Recent years have witnessed the remarkable advancement of RET fusion-positive advanced NSCLC therapy. Conventional chemotherapy produced moderate clinical benefits. Prior to the introduction of targeted therapy or in the context of unavailability, platinum-based systemic regimens are initial therapy options. Immunotherapy predicted minimal response in the presence of RET fusions while currently available data have been scarce, and the single-agent immunotherapy or in combination with chemotherapy regimens are not recommended as initial systemic therapy in this population. The repurpose of multi-target kinase inhibitors in patients with RET fusion-positive NSCLC showed encouraging therapeutic activity, with only cabozantinib and vandetanib being recommended as initial or subsequent options under certain circumstances. However, there are still unmet clinical needs. Pralsetinib and selpercatinib have been developed as tyrosine kinase inhibitors (TKI) selectively targeting RET variation of fusions or mutations, and both agents significantly improved the prognosis of patients with RET fusion-positive NSCLC. Pralsetinib and selpercatinib have been established as preferred first-line therapy or subsequent therapy options. As observed with other TKIs treatment, resistance has also been associated with RET targeted inhibition, and the acquired resistance eventually affect the long-term therapeutic effectiveness, leading to limited subsequent treatment options. Therefore, it is essential to identify resistance mechanisms to TKI in RET fusion-positive advanced NSCLC to help reveal and establish new strategies to overcome resistance. Here, we review the advances in the treatment of RET fusion-positive advanced NSCLC.
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Prepregnancy obesity status and risks on pregnancy outcomes in Shanghai: A prospective cohort study.

Obesity in women of reproductive age is not only associated with numerous adverse maternal and fetal effects prenatally but also exerts a negative influence on female fertility. The aim of this study was to investigate the situation of prepregnant obesity in Shanghai and explore the impact of prepregnant obesity on gestational weight gain as well as other pregnancy outcomes. A prospective hospital-based pregnant women cohort was established in Shanghai since January 2015. All pregnant women who were registered and expected to deliver in this hospital were included in the cohort. Nearly one fourth of pregnant women in Shanghai were overweight/obese and the prevalence of overweight/obesity was more common among women with advancing age (P < .001). Women prepregnancy overweight/obesity was associated with 3.5-fold higher risk of excessive gestational weight gain (odds ratio, OR 3.58; 95% confidence interval, CI, 2.82-4.55; P < .001). Women prepregnancy BMI was statistically related to pregnancy outcomes as macrosomia (OR 2.24; 95% CI, 1.55-3.23; P < .001), cesarean delivery (OR 2.04; 95% CI, 1.60-2.62; P < .001), maternal complications (OR 1.53; 95% CI, 1.18-1.98; P < .001). Prepregnancy obesity is associated with a much higher risk of excessive gestational weight gain and pregnancy outcomes in Shanghai. Further interventions targeting maternal obesity, especially prepregnancy obesity are required.

A red-emitting indolium fluorescence probe for membranes - flavonoids interactions.

The red-emitting indolium derivative compound (E)-2-(4-(diphenylamino)styryl)-1,3,3-trimethyl-3H-indol-1-ium iodide (H3) was demonstrated as a sensitive membrane fluorescence probe. The probe located at the interface of liposomes when mixed showed much fluorescence enhancement by inhibiting the twisted intramolecular charge transfer state. After ultrasonic treatment, it penetrated into lipid bilayers with the emissions leveling off and a rather large encapsulation efficiency (71.4%) in liposomes. The ζ-potential and particle size measurement confirmed that the charged indolium group was embedded deeply into lipid bilayers. The probe was then used to monitor the affinities of antioxidant flavonoids for membranes. It was verified that quercetin easily interacted with liposomes and dissociated the probe from the internal lipid within 60 s under the condition of simply mixing. The assessment of binding affinities of six flavonoids and the coincident results with their antioxidation activities indicated that it was a promising membrane probe for the study of drug bio-affinities.

Bone Marrow-Derived Mesenchymal Stem Cells Expressing Thioredoxin 1 Attenuate Bleomycin-Induced Skin Fibrosis and Oxidative Stress in Scleroderma.

Systemic sclerosis (SSc) is an autoimmune disorder that affects multiple organs. It is characterized by a thickening of the dermis and connective tissue caused by collagen accumulation, and vascular injuries that induce hypoxia. The present study investigated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BMSCs) expressing thioredoxin 1 (Trx-1) in treating SSc-mediated skin disease after transplantation into a bleomycin-induced murine model. Mice with bleomycin-induced SSc were subcutaneously injected with BMSCs or Trx-1-overexpressing BMSCs and exposed to hypoxic conditions for 48 hours. Two weeks later, skin tissue samples were collected to assess fibrosis, oxidative stress, and angiogenesis by western blotting, ELISA, and histologic and immunofluorescence approaches. In vivo experiments showed that Trx-1-overexpressing BMSCs inhibited hypoxia-induced apoptosis and inhibited fibrosis under hypoxic conditions, possibly by downregulating transforming growth factor-ß. Trx-1-overexpressing BMSCs also promoted the formation of tubular-like structures by endothelial progenitor cells, indicating that Trx-1 can promote angiogenesis in bleomycin-induced SSc. These results demonstrate that the transplantation of Trx-1-overexpressing BMSCs restored normal skin tissue in a mouse model of bleomycin-induced SSc, highlighting the therapeutic potential of engineered BMSCs for treating SSc.

OFF/ON Red-Emitting Fluorescent Probes for Casein Recognition and Quantification Based on Indolium Derivatives.

Five derivatives of 2, 3, 3-trimethyl-3H-indolium containing different electron donor groups (H1 - H5) were synthesized for the determination of proteins. H3, a sensitive red-emitting fluorescent probe, was found for the discrimination of hydrophobic proteins from hydrophilic. The OFF - ON fluorescence switch of H3 was caused by the formation of twisted intramolecular charge-transfer (TICT) state when it combined with hydrophobic proteins in aqueous buffer. There was a good linear relationship between the emission intensity of H3 and the casein concentration (r = 0.9989). Based on this, a novel casein quantitative assay method was developed, and the method was applied to determinate casein in milk powder samples. Successfully, the results were in good agreement with Biuret method. In addition, a simple and sensitive method was established to differentiate and quantify three casein components (α-, ß-, and κ-casein) due to their much different binding constants to H3 probe.

Right vertical infra-axillary mini-incision for repair of simple congenital heart defects: a matched-pair analysis.

OBJECTIVES: To evaluate the efficacy and safety of the right vertical infra-axillary mini-incision (RVAI) used for the repair of simple congenital heart defects. METHODS: We performed a retrospective 1:1 matched-pair analysis on the patients with simple congenital heart defects who were operated on from February 2003 to October 2010. All the recruited patients were treated through either RVAI (RVAI group) or median sternotomy incision (MSI group). In order to balance the major prognostic factors between the two groups, the MSI group was selected by a pair-matched case-control methodology and matched for heart defects, the year of surgery, body weight and patching. RESULTS: A total of 104 patients were included. The demographics and preoperative clinical characteristics of the patients in the RVAI group (n = 52) and in the MSI one (n = 52) were similar. There were no operative or late mortalities and no special care in the intensive care unit (ICU) or rehospitalization. The mean duration time of surgical operation (skin-to-skin) was 147 ± 21 min (range from 100 to 190 min) in the RVAI group and 174 ± 35 min (range from 120 to 270 min) in the MSI one (P < 0.001), respectively. No significant difference was found between the two groups in the consuming time for cardiopulmonary bypass, aortic cross-clamp, postoperative ventilation, ICU stay, postoperative hospital stay and drainage. No significant residual defects were found in patients of both groups. No asymmetrical development of the breast, thoracic deformity or scoliosis has been found during the follow-up. All the patients or the parents of young children (100%) in the RVAI group and 34 patients or the parents of young children (65.4%) in the MSI one were satisfied with the cosmetic results (P < 0.001). CONCLUSIONS: The RVAI surgical approach to simple congenital heart defects was a safe procedure and could be performed with excellent cosmetic and clinical outcomes. It provided a good alternative to the standard MSI for simple congenital heart defects.

[Clinical evaluation of the heart function early after repair of tetralogy of Fallot: follow-up of 43 patients].

OBJECTIVE: To evaluate the heart function of the patients early after the repair of tetralogy of Fallot (TOF). METHODS: Forty-three patients with TOF, 25 males and 18 females, underwent operation at the age of 2.5 - 52 years (16.7 years on average) and were followed up for 1 - 3.5 years. Twenty-one age-matched healthy persons were used as controls. Tissue Doppler imaging (TDI) was used to measure the values of the peak tricuspid ring velocity during early diastole (Ea), late diastole (Aa), systole, and isovolumic contraction, and isovolumetric contraction acceleration (IVA); and isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and isovolumetric contraction velocity (IVV) of the right ventricle. Tei index was calculated using the formula: (ICT + IRT)/ET. Treadmill test was used on the patients aged > 17 to measure the maximal heart rate maximal blood pressure, maximal exercise tolerance (MET), and movement time. RESULTS: The peak tricuspid ring velocity during Ea of the repaired TOF group (rTOF group) was 11.5 +/- 2.6 cm/s, significantly lower than that of the control group (17.1 +/- 2.4 cm/s, P < 0.0001), the peak tricuspid ring velocity during Aa of the rTOF group was 9.6 +/- 1.7 cm/s, significantly lower than that of the control group (12.9 +/- 2.9 cm/s, P < 0.001), the E/A of the rTOF group was 1.16 +/- 0.36, significantly lower than that of the control group (1.36 +/- 0.26, P < 0.05). The IVV of the rTOF group was 7.7 +/- 1.8 cm/s, significantly lower than that of the control group (9.9 +/- 1.4 cm/s, P = 0.0030, and the IVA of the rTOF group was 131.7 +/- 37.6 cm/s(2), significantly lower than that of the control group (222.5 +/- 39.2 cm/s(2), P < 0.001). The Tei index of the rTOF group was 0.58 +/- 0.11, significantly higher than that of the control group (0.52 +/- 0.04, P = 0.029). The maximal heart rate maximal blood pressure, MET, and movement time of the rTOF group were all significantly lower than those of the control group (P < 0.05 or P < 0.01). CONCLUSION: The heart function of the patients undergoing repair of TOF fails to recover to the normal level during a short time after the surgery.