Development and validation of a nomogram for predicting in-hospital mortality in ICU patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a disease with high in-hospital mortality. The objective of the present investigation was to develop and validate a nomogram that precisely anticipates in-hospital mortality in ICU individuals diagnosed with infective endocarditis. METHODS: Retrospectively collected clinical data of patients with IE admitted to the ICU in the MIMIC IV database were analyzed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential hazards. A logistic regression model incorporating multiple factors was established, and a dynamic nomogram was generated to facilitate predictions. To assess the classification performance of the model, an ROC curve was generated, and the AUC value was computed as an indicator of its diagnostic accuracy. The model was subjected to calibration curve analysis and the Hosmer-Lemeshow (HL) test to assess its goodness of fit. To evaluate the clinical relevance of the model, decision-curve analysis (DCA) was conducted. RESULTS: The research involved a total of 676 patients, who were divided into two cohorts: a training cohort comprising 473 patients and a validation cohort comprising 203 patients. The allocation ratio between the two cohorts was 7:3. Based on the independent predictors identified through LASSO regression, the final selection for constructing the prediction model included five variables: lactate, bicarbonate, white blood cell count (WBC), platelet count, and prothrombin time (PT). The nomogram model demonstrated a robust diagnostic ability in both the cohorts used for training and validation. This is supported by the respective area under the curve (AUC) values of 0.843 and 0.891. The results of the calibration curves and HL tests exhibited acceptable conformity between observed and predicted outcomes. According to the DCA analysis, the nomogram model demonstrated a notable overall clinical advantage compared to the APSIII and SAPSII scoring systems. CONCLUSIONS: The nomogram developed during the study proved to be highly accurate in forecasting the mortality of patients with IE during hospitalization in the ICU. As a result, it may be useful for clinicians in decision-making and treatment.

The Protective Effect of (-)-Tetrahydroalstonine against OGD/R-Induced Neuronal Injury via Autophagy Regulation.

Here, (-)-Tetrahydroalstonine (THA) was isolated from Alstonia scholaris and investigated for its neuroprotective effect towards oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal damage. In this study, primary cortical neurons were pre-treated with THA and then subjected to OGD/R induction. The cell viability was tested by the MTT assay, and the states of the autophagy-lysosomal pathway and Akt/mTOR pathway were monitored by Western blot analysis. The findings suggested that THA administration increased the cell viability of OGD/R-induced cortical neurons. Autophagic activity and lysosomal dysfunction were found at the early stage of OGD/R, which were significantly ameliorated by THA treatment. Meanwhile, the protective effect of THA was significantly reversed by the lysosome inhibitor. Additionally, THA significantly activated the Akt/mTOR pathway, which was suppressed after OGD/R induction. In summary, THA exhibited promising protective effects against OGD/R-induced neuronal injury by autophagy regulation through the Akt/mTOR pathway.

Patient satisfaction after nipple-sparing mastectomy with intraoperative radiotherapy and breast reconstruction for breast cancer.

INTRODUCTION: The use of nipple-sparing mastectomy (NSM) combined with breast reconstruction is increasing in breast cancer surgeries despite its controversial safety profile. To reduce the recurrence rate of tumors in the nipple-areola complex (NAC), we used intraoperative radiotherapy (IORT). The purpose of this study was to explore patients' feedback on this novel treatment strategy. PATIENTS AND METHODS: From January 2014 to May 2018, eligible patients with breast cancer were enrolled in this study and separated into 2 groups. Patients in the NSM group underwent IORT to the NAC flap, and patients in the skin-sparing mastectomy (SSM) group underwent SSM and breast reconstruction. The postoperative satisfaction was collected and assessed using the Breast-Q reconstruction questionnaire and a standardized questionnaire; this was compared between the 2 groups. RESULTS: There were 46 patients (52 NSMs) in the NSM group and 20 patients (22 SSMs) in the SSM group. The breast-Q scores were higher in the NSM group than the SSM group, with trends for a 'higher satisfaction with breasts' (67.39 ± 20.59 vs. 55.00 ± 19.33; p = 0.026) and 'higher sexual well-being' (61.74 ± 22.24 vs. 49.50 ± 20.12; p = 0.039). All the patients recognized the importance of nipple preservation. Thirty-seven women (80.40%) were satisfied or very satisfied with the appearance and shape of the NAC in the NSM group, while 38/46 women (82.60%) were very unsatisfied or unsatisfied with the sensitivity of the nipples. CONCLUSIONS: The Breast-Q scores showed great satisfaction with breasts and sexual well-being in the NSM group. However, more effort should be made in improving postoperative NAC sensitivity.

Identification of a Novel 15q21.1 Microdeletion in a Family with Marfan Syndrome.

Background: Marfan syndrome (MFS) is a connective tissue disease involving multiple systems, with thoracic aortic aneurysm (TAA) as the most common life-threatening manifestation. Method: A pedigree with TAA was investigated, and peripheral venous blood was extracted from six family members. After whole exome sequencing (WES) and chromosomal microarray analysis (CMA) in these individuals, bioinformatics and inheritance analyses were performed. Result: WES revealed a novel, small, 0.76 Mb microdeletion in 15q21.1, which cosegregated with the disease phenotype in the family and led to the haploinsufficiency of the fibrillin 1 (FBN1) gene, which is associated with MFS. This small copy number variant (CNV) was confirmed by CMA. Conclusion: Our study expands the phenotypic spectrum of the pathogenic CNV associated with MFS, thereby facilitating clinical genetic diagnosis and future genetic counseling for this family.

Host-guest complexation of cyclophosphamide by carboxylatopillar[6]arene for increasing stability and enhancing its curative effect on breast carcinoma.

Advanced chemotherapy strategies are in urgent demand for improving antitumor efficacy on breast carcinoma. Herein, a drug delivery system comprised of host-guest complex between carboxylated pillar[6]arene (CP6A) and cyclophosphamide (CTX) has been designed with view to overcoming several drawbacks associated with this antitumor agent. NMR and fluorescence titration served to confirm the complexation of CTX/CP6A. Baring CP6A did not affect cell viability as inferred from comparison studies carried out in human normal mammary epithelial cells and breast adenocarcinoma cells. Stability experiment proved that complexation of CTX by CP6A could increase the inherent stability of CTX in phosphate buffer (pH = 7.4) at 37 °C in a statistically significant way. In vivo research confirmed that CTX/CP6A was not only able to promote antitumor efficacy but also reduce CTX-related systemic toxicity on breast adenocarcinoma cells derived subcutaneous tumor xenograft mouse models. This drug delivery system could also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for more patients.

The risk factors of the early postoperative residual tricuspid regurgitation after concomitant thoracoscopic tricuspid valve repair.

OBJECTIVE: Secondary tricuspid regurgitation will be aggravated if left uncorrected during the initial surgery. Recently, an aggressive strategy of routine concomitant tricuspid valve repair has been warranted. Follow this strategy, routine concomitant thoracoscopic tricuspid valve repair was performed and the surgical effect and postoperative residual TR were reviewed. METHODS: A two-center, retrospective, observational study was conducted. Patients who underwent concomitant thoracoscopic tricuspid valve repair performed by the same surgeon between May 2012 to April 2020 were recruited into the study. The data were collected from the hospital database and outpatient records from the most recent follow-up to analysis. RESULTS: There were 504 patients recruited in this study. No death occurred and all patients were discharged. The average follow-up time was 7.4 ± 7.5 months. After the surgery, the dimension of right ventricle and pulmonary artery systolic pressure were reduced significantly. There were 11 cases (2.2%) of postoperative residual tricuspid regurgitation. Multiple logistic regression analysis revealed left atrial dimension (p = .002) and tricuspid regurgitation (p = .002) positively associated with the residual tricuspid regurgitation occurrence rate significantly. Kaplan-Meier analysis indicated the more severe the tricuspid regurgitation, the higher the residual tricuspid regurgitation occurrence rate (p < .05). CONCLUSIONS: The tricuspid valve repair surgery may improve the patients' prognosis effectively if it was performed at the appropriate timing. The larger the left atrial dimension is, or the more severe the tricuspid regurgitation is, the higher the residual tricuspid regurgitation occurrence rate after concomitant thoracoscopic tricuspid valve repair. Our experience has shown that concomitant thoracoscopic tricuspid valve repair is reliable, effective, and safe, which may be beneficial to right heart remodeling in the short to midterm.

miR-145-5p Suppresses Breast Cancer Progression by Inhibiting SOX2.

BACKGROUND: In this study, we aimed to investigate the expression and clinical significance of miR-145-5p and its tumor-suppressive effect in breast cancer patients. METHODS: We used luciferase reporter assay, real-time quantitative reverse transcription polymerase chain reaction and Western blot to identify sex-determining region Y-box2 (SOX2) as the target gene of miR-145-5p. Their expression levels in breast cancer tissues (n = 122) were detected by real-time quantitative polymerase chain reaction. We also applied 3-(4,5-dimethyl- 2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry to reveal the effect of miR-145-5p on proliferation in breast cancer. RESULTS: miR-145-5p expression is downregulated in breast cancer tissues and negatively correlated with SOX2 expression. Decreased miR-145-5p expression was significantly associated with larger tumor size, distal metastasis, higher Ki67 expression level, and shorter overall survival. miR-145-5p inhibits breast cancer cell proliferation via targeting SOX2, and multivariate regression showed that both miR-145-5p and SOX2 were unfavorable prognostic factors. CONCLUSIONS: miR-145-5p played a suppressive role in the proliferation of breast cancer cells by targeting SOX2, and miR-145-5p is a putative biomarker for risk assessment in patients with breast cancer.

Intraoperative Implantation of Temporary Endocardial Pacing Catheter During Thoracoscopic Redo Tricuspid Surgery.

BACKGROUND: The placement of a temporary epicardial pacing wire is a challenge during a minimally invasive redo cardiac operation. The aim of this study is to assess the application of temporary endocardial pacing in patients who underwent minimally invasive redo tricuspid surgery. METHODS: Perioperative data of consecutive patients who underwent thoracoscopic redo tricuspid surgery were collected. All the tricuspid surgeries and combined procedures were performed under peripheral cardiopulmonary bypass without aortic cross-clamping. A sheath was introduced into the right jugular vein beside the percutaneous superior vena cava cannula and a temporary endocardial pacing catheter was guided into the right ventricle via the sheath prior to the right atrial closure. The pacemaker was connected and run as needed during or after operation. RESULTS: A total of 33 patients who underwent thoracoscopic redo tricuspid surgery were enrolled. Symptomatic tricuspid valve regurgitation (93.9%) and tricuspid valvular prosthesis obstruction (6.1%) after previous cardiac operations were noted as indications for a redo surgery. The mean time from previous cardiac operation to this time redo surgery was 13.3±6.4years. Isolated tricuspid valve replacement was performed in 18 patients (54.5%) and tricuspid valve plasty combined with or without mitral valve replacement was performed in 15 patients (45.5%). A temporary endocardial pacing catheter was successfully placed in the right ventricle for all patients with good sensing and pacing. No temporary pacing related complications occurred from insertion to removal of pacing catheter in the patients. CONCLUSIONS: This application of temporary endocardial pacing provided a safe and effective substitute for epicardial pacing in patients who underwent minimally invasive redo tricuspid surgery.

Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies.

Rose bengal (RB) is a halogenated xanthene dye that has been used to mediate antimicrobial photodynamic inactivation for several years. While RB is highly active against Gram-positive bacteria, it is largely inactive in killing Gram-negative bacteria. We have discovered that addition of the nontoxic salt potassium iodide (100 mM) potentiates green light (540-nm)-mediated killing by up to 6 extra logs with the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium methicillin-resistant Staphylococcus aureus, and the fungal yeast Candida albicans The mechanism is proposed to be singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes into radicals and, finally, forms hydrogen peroxide and molecular iodine. The effects of these different bactericidal species can be teased apart by comparing the levels of killing achieved in three different scenarios: (i) cells, RB, and KI are mixed together and then illuminated with green light; (ii) cells and RB are centrifuged, and then KI is added and the mixture is illuminated with green light; and (iii) RB and KI are illuminated with green light, and then cells are added after illumination with the light. We also showed that KI could potentiate RB photodynamic therapy in a mouse model of skin abrasions infected with bioluminescent P. aeruginosa.

Improvement in the Anticancer Activity of 6-Mercaptopurine via Combination with Bismuth(III).

6-Mercaptopurine (6-MP) is a clinically important antitumor drug and its commercially available form is provided as monohydrate, belonging to biopharmaceuticals classification system (BCS) class II category. The combination of bismuth(III) (Bi(III)) with 6-MP was proved to significantly improve the anticancer activity of 6-MP, leading to the discovery of a new amorphous complex ([Bi(MP)3(NO3)2]NO3). The prepared [Bi(MP)3(NO3)2]NO3 was characterized by the matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF)-MS, etc. Noticeably, according to the in vitro evaluations of cytotoxicity, cellular apoptotic, colony formation as well as cell migration, the anticancer activity of amorphous [Bi(MP)3(NO3)2]NO3 was found to be of high therapeutic effect over 6-MP.

Bilateral subclavian vein sheaths for superior vena cava drainage during thoracoscopic repair of atrial septal defects: cosmetic outcomes, safety and effectiveness.

OBJECTIVE: To investigate the cosmetic outcomes, safety and effectiveness of using bilateral subclavian vein sheaths for superior vena cava drainage during thoracoscopic repair of atrial septal defects. METHODS: Sixty-one consecutive adults scheduled for thoracoscopic repair of atrial septal defects between July 2012 and June 2013 were randomized into two groups: one group underwent placement of a 16 Fr percutaneous superior vena cava cannula (n = 30) and the other group underwent placement of bilateral 8 Fr subclavian vein sheaths (n = 31) for superior vena cava drainage during peripheral cardiopulmonary bypass. The perioperative data, central venous pressure during cardiopulmonary bypass, complications and the patient satisfaction scale scores for the incisions were compared between the two groups. RESULTS: The theoretical cardiopulmonary bypass flow rate was reached without complications in all patients. The average central venous pressure during cardiopulmonary bypass was not significantly different between the two groups [(6.9 ± 3.1) mmHg vs. (7.0 ± 3.5) mmHg, p=0.92]. The patient satisfaction scale scores for the incisions were significantly higher in the patients who underwent placement of bilateral subclavian vein sheaths than in the patients who underwent placement of a percutaneous superior vena cava cannula [(2.81 ± 0.75) vs. (2.07 ± 0.74), p<0.001]. CONCLUSIONS: Placement of bilateral subclavian vein sheaths is a safe and effective alternative to placement of a percutaneous superior vena cava cannula for superior vena cava drainage during thoracoscopic repair of atrial septal defects and results in greater patient satisfaction with the cosmetic outcome.

Transcriptome analysis of the variations between autotetraploid Paulownia tomentosa and its diploid using high-throughput sequencing.

Timber properties of autotetraploid Paulownia tomentosa are heritable with whole genome duplication, but the molecular mechanisms for the predominant characteristics remain unclear. To illuminate the genetic basis, high-throughput sequencing technology was used to identify the related unigenes. 2677 unigenes were found to be significantly differentially expressed in autotetraploid P. tomentosa. In total, 30 photosynthesis-related, 21 transcription factor-related, and 22 lignin-related differentially expressed unigenes were detected, and the roles of the peroxidase in lignin biosynthesis, MYB DNA-binding proteins, and WRKY proteins associated with the regulation of relevant hormones are extensively discussed. The results provide transcriptome data that may bring a new perspective to explain the polyploidy mechanism in the long growth cycle of plants and offer some help to the future Paulownia breeding.

Lymphangiogenesis in gastric cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis.

BACKGROUND: Lymphangiogenesis plays a significant role in metastasis and recurrence of gastric cancer. There is no report yet focusing on the modulation of VEGF pathway and lymphangiogenesis of gastric cancer by targeting Akt/mTOR pathway. This study aims to demonstrate the relationship between Akt/mTOR pathway and VEGF-C/-D in gastric cancer. METHODS: We collected surgically resected gastric adenocarcinoma specimens from 55 consented patients. Immunohistochemistry staining of p-Akt, p-mTOR, VEGF-C, VEGF-D were performed and scored by two independent pathologists. The results were presented as staining intensity and positive staining cell rate. We also measured lymphatic vessel density (LVD) by D2-40 staining. Different dosages of p-Akt inhibitor LY294002 (12.5 µM, 25 µM, 50 µM) and p-mTOR inhibitor Rapamycin (25 nM, 50 nM, 100 nM) were given to gastric cancer cell line SGC-7901 in vitro. The inhibition rate of cell growth was tested by MTT at 24 h, 48 h and 72 h, respectively and protein expressions of Akt, p-Akt, mTOR, p-mTOR, VEGF-C and VEGF-D were examined by Western blot. RESULTS: The positive staining rates of p-Akt, p-mTOR, VEGF-C and VEGF-D in 55 gastric cancer clinical specimens were 74.54%, 85.45%, 72.73% and 58.18%. p-Akt and p-mTOR were positively correlated with VEGF-C and VEGF-D (p < 0.01). The LVD increased with incremental tendency of staining intensity of p-Akt, p-mTOR, VEGF-C and VEGF-D. LY294002 or Rapamycin significantly suppressed SGC-7901 cell growth and the inhibition rate was dose and time dependent (p < 0.001). In addition, the protein expression of p-Akt and p-mTOR were positively correlated with that of VEGF-C and VEGF-D (p < 0.05). CONCLUSIONS: The level of LVD in gastric cancer specimens was significant higher than that of normal gastric tissue and was positively correlated with p-Akt, p-mTOR, VEGF-C and VEGF-D. Inhibition of p-Akt and p-mTOR, in vitro, decreased tumor cell VEGF-C and VEGF-D significantly. Therefore, we concluded that lymphangiogenesis of gastric cancer might be related to Akt/mTOR-VEGF-C/VEGF-D axis.

Prognostic value of miR-106b expression in breast cancer patients.

BACKGROUND: The aim of the present study was to evaluate whether the level of expression of tissue or plasma miR-106b can be used to predict clinical outcomes in breast cancer patients. METHODS: Both tissue and plasma samples were collected and analyzed from 173 patients with primary breast cancer and a set of 50 women with fibroadenoma. The relative expression levels of miR-106b were determined using real-time quantitative reverse transcription polymerase chain reaction and in situ hybridization. RESULTS: The levels of miR-106b were upregulated in both tissue and plasma samples from breast cancer patients. The expression levels showed a linear correlation (rs = 0.748, P < 0.001) and were significantly correlated with tumor size, Ki67 expression, and lymph node metastasis (all P < 0.05). Patients with high miR-106b expression levels tended to have shorter disease-free survival times and overall survival times (P < 0.001). In a Cox regression model, high-level tissue and plasma miR-106b expression were unfavorable prognostic factors, and receiver-operating characteristic analysis revealed that the tissue and plasma miR-106b levels provided considerable diagnostic accuracy, yielding an area under the ROC curve of 0.785 and 0.856, respectively. CONCLUSIONS: MiR-106b was found to be associated with a high risk of recurrence of breast cancer, and miR-106b is a putative plasma marker for risk assessment in patients with breast cancer.

Anomalous Origin of One Pulmonary Artery Branch From the Aorta: Role of MDCT Angiography.

OBJECTIVE: The purpose of this study was to evaluate the prevalence, MDCT angiography (MDCTA) appearance, associated congenital cardiovascular abnormalities, and prognosis of anomalous origin of one pulmonary artery from the aorta (AOPA) on the basis of MDCTA. MATERIALS AND METHODS: We conducted a retrospective search of patients with AOPA from our database in a single center, consisting of 5729 patients referred for MDCTA with known or suspected congenital heart diseases from transthoracic echocardiography. The clinical information, subtypes of AOPA, associated cardiovascular anomalies, and surgical and clinical outcomes were retrospectively collected and analyzed. The MDCTA images were retrospectively processed for analysis, and the MDCTA and echocardiography images were interpreted by radiologist and cardiologist without knowledge of the actual diagnosis or surgical outcome. RESULTS: AOPA was seen in 19 patients (14 males and five females; median age, 3 months; range, 4 days-21 years) showing a prevalence of 0.33%. Anomalous origin of the right pulmonary artery (AORPA, 89%), proximal origin subtype of the AOPA (89%), and ipsilateral aortic wall origin of AOPA (58%) were more commonly seen. In addition to the benefit of preoperative planning, MDCTA also supplemented echocardiography by providing accurate diagnosis of AOPA and other associated cardiovascular anomalies compared with transthoracic echocardiography (TTE). We found a total of four patients (21%) with misdiagnosis by TTE, including three patients with underdiagnosis of AOPA and one patient with misdiagnosis as transposition of the great arteries. In addition, two other patients had AOPA diagnosed, but the associated patent ductus arteriosus (PDA) was not detected. MDCTA revealed 95% association with other congenital cardiovascular anomalies, including PDA (71% of AORPA), and aortic arch anomalies (100% of anomalous origin of the left pulmonary artery, AOLPA). The types of surgery depended on the MDCTA findings, including the sub-type, origin sites of AOPA, and associated cardiovascular anomalies. Analysis of the pulmonary arterial sizes showed the McGoon ratios in these patients with a median value of 2.4 (range, 1.5-2.9). Surgical treatment performed before the age of 1 year enabled normalization of pulmonary artery pressure in 92% of patients. CONCLUSION: AOPA had a prevalence of 0.33% among patients with congenital heart disease in our series. MDCTA was an important supplement for the diagnosis, delineating the different subtypes and origin sites of AOPA and permitting preoperative planning of AOPA in patients suspected on the basis of echocardiography of having AOPA because accurate diagnosis and early surgical treatment remain the mainstays in improving patient outcome.

Evaluation of malposition of the branch pulmonary arteries using cardiovascular computed tomography angiography.

OBJECTIVES: To analyze 15 cases of malposition of branch pulmonary arteries (MBPA) for the hospital-based prevalence, clinical information, surgical outcome, imaging findings, associated cardiovascular and airway abnormalities on cardiovascular computed tomography angiography (CCTA). METHODS: We retrospectively searched for patients with MBPA from our database consisting of patients referred for CCTA due to known or suspected congenital heart disease and also from all patients receiving chest computed tomography (CT) during the same time period. We analyzed the hospital-based prevalence, image findings, associated cardiovascular anomalies, airway compression, and recorded the clinical information and surgical outcome. RESULTS: Our study showed 15 patients with MBPA (hospital-based prevalence: 0.33% among patients with congenital heart disease and 0.06% in all patients receiving chest CT or CCTA). Classic type was more common than lesser type (67% versus 33%). All patients had associated cardiovascular anomalies, including aortic arch abnormalities (80%) and secondary airway compression (33%). Surgery was performed in 67% of cardiovascular anomalies and 60% of airway stenoses. CONCLUSIONS: MBPA has a hospital-based prevalence of 0.33% among patients with congenital heart disease and 0.06% in all patients receiving either chest CT or CCTA. CCTA can delineate the anatomy of MBPA, associated cardiovascular and airway abnormalities for preoperative evaluation. KEY POINTS: MBPA has a hospital-based prevalence of 0.33% among congenital heart disease patients. Classic type of MBPA was more common than lesser type. All MBPA patients had associated cardiovascular anomalies, 33% had secondary airway compression. CCTA delineates the anatomy of MBPA, associated cardiovascular and airway abnormalities. CCTA is beneficial in MBPA for preoperative evaluation and planning.

Superior vena cava drainage during thoracoscopic cardiac surgery: bilateral internal jugular vein sheaths versus one percutaneous superior vena cava cannula.

OBJECTIVE: To evaluate bilateral internal jugular vein sheaths as a replacement of one percutaneous superior vena cava cannula for superior vena cava drainage during thoracoscopic cardiac surgery. DESIGN: A prospective and randomized study. SETTING: Single cardiovascular institute. PARTICIPANTS: Adults undergoing thoracoscopic cardiac surgery. INTERVENTIONS: Patients were randomized into a percutaneous superior vena cava cannula group and a bilateral internal jugular vein sheaths group. The superior vena cava drainage for cardiopulmonary bypass was performed with one percutaneous superior vena cava cannula (14-18 Fr) or the bilateral internal jugular vein sheaths (8 Fr). MEASUREMENTS AND MAIN RESULTS: Both interventions reached theoretic flow rate in all patients. In patients weighing<50 kg (n=38) and 50-70 kg (n=64), the average central venous pressure values during cardiopulmonary bypass of both groups showed no significant differences. The patients weighing>70 kg (n=15) in the bilateral internal jugular vein sheaths group had a normal average central venous pressure value, but it was significantly higher than that of percutaneous superior vena cava cannula group ([10.5±3.1] mmHg vs. [4.5±4.4] mmHg, p=0.013). The patient satisfaction scale scores for the cervical incisions were significantly higher in the bilateral internal jugular vein sheaths group than in the percutaneous superior vena cava cannula group ([2.6±0.9] vs. [2.1±0.8], p=0.002). CONCLUSIONS: The bilateral internal jugular vein sheaths were a feasible and effective option to replace one percutaneous superior vena cava cannula during thoracoscopic cardiac surgery, with better patient satisfaction.

Differential transcriptome analysis between Paulownia fortunei and its synthesized autopolyploid.

Paulownia fortunei is an ecologically and economically important tree species that is widely used as timber and chemical pulp. Its autotetraploid, which carries a number of valuable traits, was successfully induced with colchicine. To identify differences in gene expression between P. fortunei and its synthesized autotetraploid, we performed transcriptome sequencing using an Illumina Genome Analyzer IIx (GAIIx). About 94.8 million reads were generated and assembled into 383,056 transcripts, including 18,984 transcripts with a complete open reading frame. A conducted Basic Local Alignment Search Tool (BLAST) search indicated that 16,004 complete transcripts had significant hits in the National Center for Biotechnology Information (NCBI) non-redundant database. The complete transcripts were given functional assignments using three public protein databases. One thousand one hundred fifty eight differentially expressed complete transcripts were screened through a digital abundance analysis, including transcripts involved in energy metabolism and epigenetic regulation. Finally, the expression levels of several transcripts were confirmed by quantitative real-time PCR. Our results suggested that polyploidization caused epigenetic-related changes, which subsequently resulted in gene expression variation between diploid and autotetraploid P. fortunei. This might be the main mechanism affected by the polyploidization. Our results represent an extensive survey of the P. fortunei transcriptome and will facilitate subsequent functional genomics research in P. fortunei. Moreover, the gene expression profiles of P. fortunei and its autopolyploid will provide a valuable resource for the study of polyploidization.

Single-cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non-small-cell lung cancer.

BACKGROUND: Recurrent malignant pleural effusion (MPE) resulting from non-small-cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain. METHODS: 16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non-recurrent or recurrent MPE was determined after 3-6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single-cell RNA sequencing (scRNA-seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64). RESULTS: The scRNA-seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin-4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal-type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver-gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non-recurrent group, which was also associated with a trend towards worse overall survival (OS). CONCLUSIONS: CLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in-depth mechanism studies on its biological function are warranted. TRIAL REGISTRATION: Not applicable.

In-depth proteomic analysis identifies key gene signatures predicting therapeutic efficacy of anti-PD-1/PD-L1 monotherapy in non-small cell lung cancer.

Background: Immunotherapy has opened up a new era of individualized treatment for non-small cell lung cancer (NSCLC) with negative driver gene mutations. Anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies have been the main options for immunotherapy over the past decade. Screening for predictive markers of anti-PD-1/PD-L1-responsive patients remains a focus in the field of immunotherapy, especially on the protein level in which relevant proteomic biomarkers are still lacking. Methods: We collected samples from 23 patients with NSCLC who received anti-PD-1/PD-L1 monotherapy and were followed up for three years. The proteomic profile of the tumor was obtained by mass spectrometry (MS). Meanwhile, we combined the RNA sequencing (RNA-seq) data of 27 patients treated with anti-PD-1/PD-L1 therapy in a previous study to establish an integrated gene network. Weighted correlation network analysis (WGCNA) and elastic network were implemented to screen the top gene modules for predicting treatment-responsive patients. Gene expression related mutational patterns were also retrieved for validation in the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort. Results: Our results showed the gene expression profile of MOXD1, PHAF1, KRT7, ANKRD30A, TMEM184A, KIR3DL1, and KCNK4 could better predict the durable response to anti-PD-1/PD-L1 therapy, with the specificity and sensitivity of 0.76 and 0.6, respectively. Besides, the mutational gene profile associated with these genes also suggested an association with favorable response in the MSKCC cohort. Patient-specific protein-protein interaction (PPI) network also indicated strong correlation among KRT7, TMEM184A and ANKRD30A. Conclusions: Our study indicated that key gene signatures identified by machine learning model could be utilized for clinical screening of patients who might benefit from anti-PD-1 therapy. Further mechanistic investigations around these genes are warranted.