Elucidating the role of tumor-associated ALOX5+ mast cells with transformative function in cervical cancer progression via single-cell RNA sequencing.

Background: Cervical cancer (CC) is the fourth most common malignancy among women globally and serves as the main cause of cancer-related deaths among women in developing countries. The early symptoms of CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there is a close relationship between mast cells (MCs) and tumor development. However, research on the role MCs played in CC is still very limited at that time. Thus, the study conducted a single-cell multi-omics analysis on human CC cells, aiming to explore the mechanisms by which MCs interact with the tumor microenvironment in CC. The goal was to provide a scientific basis for the prevention, diagnosis, and treatment of CC, with the hope of improving patients' prognoses and quality of life. Method: The present study acquired single-cell RNA sequencing data from ten CC tumor samples in the ArrayExpress database. Slingshot and AUCcell were utilized to infer and assess the differentiation trajectory and cell plasticity of MCs subpopulations. Differential expression analysis of MCs subpopulations in CC was performed, employing Gene Ontology, gene set enrichment analysis, and gene set variation analysis. CellChat software package was applied to predict cell communication between MCs subpopulations and CC cells. Cellular functional experiments validated the functionality of TNFRSF12A in HeLa and Caski cell lines. Additionally, a risk scoring model was constructed to evaluate the differences in clinical features, prognosis, immune infiltration, immune checkpoint, and functional enrichment across various risk scores. Copy number variation levels were computed using inference of copy number variations. Result: The obtained 93,524 high-quality cells were classified into ten cell types, including T_NK cells, endothelial cells, fibroblasts, smooth muscle cells, epithelial cells, B cells, plasma cells, MCs, neutrophils, and myeloid cells. Furthermore, a total of 1,392 MCs were subdivided into seven subpopulations: C0 CTSG+ MCs, C1 CALR+ MCs, C2 ALOX5+ MCs, C3 ANXA2+ MCs, C4 MGP+ MCs, C5 IL32+ MCs, and C6 ADGRL4+ MCs. Notably, the C2 subpopulation showed close associations with tumor-related MCs, with Slingshot results indicating that C2 subpopulation resided at the intermediate-to-late stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. CNVscore and bulk analysis results further confirmed the transforming state of the C2 subpopulation. CellChat analysis revealed TNFRSF12A as a key receptor involved in the actions of C2 ALOX5+ MCs. Moreover, in vitro experiments indicated that downregulating the TNFRSF12A gene may partially inhibit the development of CC. Additionally, a prognosis model and immune infiltration analysis based on the marker genes of the C2 subpopulation provided valuable guidance for patient prognosis and clinical intervention strategies. Conclusions: We first identified the transformative tumor-associated MCs subpopulation C2 ALOX5+ MCs within CC, which was at a critical stage of tumor differentiation and impacted the progression of CC. In vitro experiments confirmed the inhibitory effect of knocking down the TNFRSF12A gene on the development of CC. The prognostic model constructed based on the C2 ALOX5+MCs subset demonstrated excellent predictive value. These findings offer a fresh perspective for clinical decision-making in CC.

Case report: Cytokine and miRNA profiling in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is an imperative pediatric inflammatory condition closely linked to COVID-19, which garners substantial attention since the onset of the pandemic. Like Kawasaki illness, this condition is characterized by an overactive immune response, leading to symptoms including pyrexia, cardiac and renal complications. To elucidate the pathogenesis of MIS-C and identify potential biomarkers, we conducted an extensive examination of specific cytokines (IL-6, IL-1ß, IL-6R, IL-10, and TNF-α) and microRNA (miRNA) expression profiles at various intervals (ranging from 3 to 20 days) in the peripheral blood sample of a severely affected MIS-C patient. Our investigation revealed a gradual decline in circulating levels of IL-6, IL-1ß, IL-10, and TNF-α following intravenous immune globulin (IVIG) therapy. Notably, IL-6 exhibited a significant reduction from 74.30 to 1.49 pg./mL, while IL-6R levels remained consistently stable throughout the disease course. Furthermore, we observed an inverse correlation between the expression of hsa-miR-596 and hsa-miR-224-5p and the aforementioned cytokines. Our findings underscore a robust association between blood cytokine and miRNA concentrations and the severity of MIS-C. These insights enhance our understanding of the genetic regulatory mechanisms implicated in MIS-C pathogenesis, offering potential avenues for early biomarker detection and therapy monitoring through miRNA analysis.

COVID-19 Vaccination in Pregnancy: Pilot Study of Plasma MicroRNAs Associated with Inflammatory Cytokines after COVID-19 mRNA Vaccination.

BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.

A state feedback control with compensation for permanent magnet synchronous machine drives.

Using the linear approach to design a controller is still prevalent. The state feedback control (SFC) is applied in this paper to improve the dynamic response of permanent magnet synchronous machine (PMSM) speed regulation systems. First, a third-order augmented system is constructed for the reason that a higher-order system has better disturbance rejection. It can be found through analysis and comparison that the order of the proposed speed controller is increased. The parameters of SFC are selected by utilizing the linear quadratic regulator (LQR), and the influence of matrix Q on dynamic performance is detailed through the Bode diagram. Additionally, considering parametric uncertainties and unmodeled dynamics, a disturbance observer (DOB) using the Luenberger observer is designed to further boost anti-disturbance performance. Finally, plenty of experimental results verify the effectiveness of the proposed methods.

Comparison of ICG-Guided Near-Infrared Fluorescence Imaging and Modified Inflation-Deflation Method in Identifying the Intersegmental Plane During Lung Segmentectomy of Infants.

BACKGROUND: The identification of the intersegmental plane (ISP) is a crucial step in segmentectomy for children with congenital pulmonary airway malformation (CPAM) due to complex anatomical variations. However, there is very limited literature available on this aspect specifically for infant. In this study, we compared the intravenous indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) imaging method with the modified inflation-deflation method in terms of their perioperative characteristics and summarized our experience. METHODS: From June 2021 to November 2022, the data of 83 patients with CPAM who underwent segmentectomy by video-assisted thoracoscopic surgery were retrospectively reviewed. Twenty-eight patients underwent ICG-guided NIRF method, and 56 patients underwent the modified inflation-deflation method, characteristics and clinical outcomes were compared. RESULTS: The median age of the patients was 4.99 months (4.99 ± 1.51) with a mean body weight of 7.54 kg (7.54 ± 1.99). Both methods could accurately identify the ISP. The time taken to clearly display the ISP was shorter in ICG group than in the modified inflation-deflation group (0.18 ± 0.08 vs. 6.49 ± 1.67 min; P < 0.001), and the surgical duration (61.32 ± 14.28 vs. 88.18 ± 8.03 min; P < 0.001) were significantly shorter in the ICG group too. The two groups exhibited differences in the length of chest tube drainage (1.75 ± 1.24 vs. 2.36 ± 1.54 days; P = 0.072) and the length of hospital stay (4.61 ± 1.75 vs. 5.20 ± 3.07 days; P = 0.078), however, the differences were not statistically significant. There were no significant differences between the two groups in the blood lost and postoperative complications. At a follow-up of more than 1 year after operation, all patients had recovered well without recurrence. CONCLUSIONS: According to our experience, the ICG-guided NIRF method was safe and feasible for infants during thoracoscopic segmentectomy, it can quickly display the ISP and shorten the surgical duration compared with the modified inflation-deflation method.

Different Dosages of Progesterone in Luteal Phase Support Reflect Varying Endometrial microRNA Expression in Frozen Embryo Transfer Cycles.

Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients' miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF.

A composite sliding mode control with the first-order differentiator and sliding mode observer for permanent magnet synchronous machine.

This paper proposes a composite sliding mode control (SMC) to optimize the tracking performance and the anti-disturbance performance of permanent magnet synchronous machine (PMSM) speed regulation systems. The differential term in the control law can magnify the measurement noise, resulting in more discontinuity. To filter out the high frequency noise and make the control law smoother, the first-order differentiator (FOD) is employed to estimate the speed error and its derivative. Since the feedforward compensation can improve the robustness of the system, a disturbance observer (DOB) based on the sliding mode observer (SMO) is designed to reinforce the dynamic performance under disturbance variation. Under the effect of the feedforward compensation, chattering can be further weakened by decreasing the switching gain appropriately. Finally, the effectiveness of the proposed methods is confirmed by various experimental results.

Deterministic nuclear reprogramming of mammalian nuclei to a totipotency-like state by Amphibian meiotic oocytes for stem cell therapy in humans.

The ultimate aim of nuclear reprogramming is to provide stem cells or differentiated cells from unrelated cell types as a cell source for regenerative medicine. A popular route towards this is transcription factor induction, and an alternative way is an original procedure of transplanting a single somatic cell nucleus to an unfertilized egg. A third route is to transplant hundreds of cell nuclei into the germinal vesicle (GV) of a non-dividing Amphibian meiotic oocyte, which leads to the activation of silent genes in 24 h and robustly induces a totipotency-like state in almost all transplanted cells. We apply this third route for potential therapeutic use and describe a procedure by which the differentiated states of cells can be reversed so that totipotency and pluripotency gene expression are regained. Differentiated cells are exposed to GV extracts and are reprogrammed to form embryoid bodies, which shows the maintenance of stemness and could be induced to follow new directions of differentiation. We conclude that much of the reprogramming effect of eggs is already present in meiotic oocytes and does not require cell division or selection of dividing cells. Reprogrammed cells by oocytes could serve as replacements for defective adult cells in humans.

Near-Infrared Fluorescence Imaging with Intravenous Indocyanine Green Method in Segmentectomy for Infants with Congenital Pulmonary Airway Malformation.

BACKGROUND: Video-assisted thoracoscopic surgery is a commonly used procedure for treating congenital pulmonary airway malformation (CPAM) in infants, particularly when performing segmentectomy for segmental lesions. An innovative technique employing near-infrared fluorescence (NIRF) imaging with intravenous indocyanine green (ICG) has been utilized to delineate the intersegmental demarcation during surgery. However, no previous reports have investigated this method's application, specifically in infants. The primary aim of this study was to assess the safety and efficacy of the NIRF imaging with ICG approach in this context. METHODS: Between January 2021 and April 2022, a total of 19 consecutive segmentectomies were conducted using the NIRF imaging with ICG method to precisely identify the intersegmental plane. The results were concurrently compared with those obtained using the modified inflation-deflation technique. Comprehensive imaging and clinical data were gathered and analyzed to assess the safety and accuracy of the NIRF imaging with ICG approach. RESULTS: The study involved infants with a median age of 5.12 months (mean body weight of 8.08 g). All segmentectomies were performed successfully without any ICG-related complications. The mean operating time for the surgeries was 88.47 ± 7.94 minutes. Notably, no intraoperative conversions or significant complications were observed in any of the patients. The average hospital stay after surgery was 4.0 ± 0.82 days. During the follow-up period, extending beyond 1-year of postoperation, all patients exhibited excellent recovery with no cases of recurrence. CONCLUSIONS: Based on our experience, the NIRF imaging with intravenous ICG method proved to be both safe and effective when performing segmentectomy for infants with CPAM. Low doses of ICG did not hinder the accurate identification of the intersegmental plane.

Glycolysis regulation in tumor-associated macrophages: Its role in tumor development and cancer treatment.

Tumor-associated macrophages constitute the main cell population in the tumor microenvironment and play a crucial role in regulating the microenvironment composition. Emerging evidence has revealed that the metabolic profile determines the tumor-associated macrophage phenotype. Tumor-associated macrophage function is highly dependent on glucose metabolism, with glycolysis being the major metabolic pathway. Recent reports have demonstrated diversity in glucose flux of tumor-associated macrophages and complex substance communication with cancer cells. However, how the glucose flux in tumor-associated macrophages connects with glycolysis to influence tumor progression and the tumor microenvironment is still obscure. Moreover, while the development of single-cell sequencing technology allows a clearer and more accurate classification of tumor-associated macrophages, the metabolic profiles of tumor-associated macrophages from the perspective of single-cell omics has not been well summarized. Here, we review the current state of knowledge on glucose metabolism in tumor-associated macrophages and summarize the metabolic profiles of different tumor-associated macrophage subtypes from the perspective of single-cell omics. Additionally, we describe the current strategies targeting glycolysis in tumor-associated macrophages for cancer therapy.

COVID-19 Vaccination in Pregnancy: Pilot Study for Maternal and Neonatal MicroRNA Profiles.

This pilot study explores alterations in miRNA profiles among pregnant women and their neonates upon receiving different doses of COVID-19 vaccines. Blood samples, including maternal blood (MB) and neonatal cord blood (CB), collected from five pregnant women were scrutinized using the miRNA PanelChip Analysis System, identifying nine distinct miRNAs, including miR-451a and miR-1972, which exhibited significant downregulation with two vaccine doses in both MB and CB. When compared with women vaccinated with four doses, miR-486-5p, miR-451a, and miR-1972 in the two-dose group also showed notable downregulation. Evaluating recipients of three and four doses, miR-423-5p and miR-1972 expression were significantly reduced in both MB and CB. Further comparative analysis highlighted a decline in miR-223-3p expression with increasing vaccine doses, while miR15a-5p, miR-16-5p, and miR-423-5p showed an upward trend. Notably, miR-451a, miR-1972, and miR-423-5p levels varied across doses and were associated with pathways such as "PI3K-Akt", "neurotrophin signaling", and "cortisol synthesis", suggesting the profound influence of vaccination on diverse molecular mechanisms. Our research has uncovered that escalating vaccine dosages impact miRNA profiles, which may be associated with the immunological response mechanisms in both the mother and fetus, thus indicating a substantial impact of vaccination on various molecular processes.

Computed tomography imaging-guided parasternal approach drainage for children with tension pneumomediastinum: a case series.

PURPOSE: Tension pneumomediastinum is a rare and dangerous complication in children that can be fatal, and timely detection and treatment are critical. The aim of this study was to evaluate the safety and feasibility of computed tomography (CT) imaging-guided parasternal approach drainage for tension pneumomediastinum in children. METHODS: From June 2018 to February 2023, we consecutively enrolled 19 children with tension pneumomediastinum in our institution. A pigtail catheter was inserted into the anterior mediastinum by a CT imaging-guided parasternal approach. The catheter was connected to a negative-pressure water seal bottle to drain the pneumomediastinum. Clinical data and outcomes were summarized. RESULTS: The mean age was 3.1 ± 3.4 years, the mean weight was 15 ± 9.1 kg, the mean procedure time was 11.8 ± 2.4 min, and the drainage time was 6.7 ± 3.4 days. No major complications were identified, such as haemothorax, catheter displacement, or mediastinal infection. Effective drainage was obtained in all patients as assessed by comparing images and ventilatory parameters, and no additional surgical treatment was needed. There was no recurrence during the follow-up, which was more than 2 months. In our data, two children with COVID-19 were discharged from the hospital after effective drainage and other clinical treatment. CONCLUSION: CT-guided parasternal approach drainage is safe, minimally invasive, and effective for children with tension pneumomediastinum.

Successful extracorporeal membrane oxygenation for postoperative cardiopulmonary failure in newborns with congenital diaphragmatic hernia: case reports and literature reviews.

Introduction: Congenital diaphragmatic hernia (CDH) is a structural defect caused by inadequate fusion of the pleuroperitoneal membrane that forms the diaphragm, allowing peritoneal viscera to protrude into the pleural cavity. Up to 30% of newborns with CDH require extracorporeal membrane oxygenation (ECMO) support. As with all interventions, the risks and benefits of ECMO must be carefully considered in these patients. Cardiopulmonary function has been shown to worsen rather than improve after surgical CDH repair. Even after a detailed perioperative assessment, sudden cardiopulmonary failure after surgery is dangerous and requires timely and effective treatments. Method: Three cases of cardiopulmonary failure after surgical CDH treatment in newborns have been reported. ECMO support was needed for these three patients and was successfully discontinued. We report our treatment experience. Conclusion: ECMO is feasible for the treatment of postoperative cardiopulmonary failure in newborns with CDH.

A potential cause of left ventricular dysfunction after surgery in neonates with low-risk congenital diaphragmatic hernia: high-tension repair.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a serious congenital malformation. Given the focus on improving survival in patients with "high-risk" CDH, it is possible that risk factors for low-risk patient with CDH may not be a concern. Left heart failure leads to adverse postoperative outcomes, including the need for extracorporeal membrane oxygenation (ECMO). The purpose of this study was to explore the causes of postoperative left heart failure in the low-risk group. METHODS: A retrospective study was conducted on newborns with congenital diaphragmatic hernia who were surgically treated in our hospital from January 2018 to March 2022. Children at low risk were divided into three groups according to the intraoperative repair conditions. Group A was defined as grade A defects repaired by direct suture. Group B was defined as a grade B defect repaired by mesh. Group C was a grade B defect repaired by high-tension suture. The age, gender, weight, perioperative echocardiography, and follow-up of the patients were statistically analyzed. The risk factors of left ventricular dysfunction after surgery in neonates with low-risk congenital diaphragmatic hernia were analyzed. RESULTS: A total of 52 low-risk children were included in the study. For children in the low-risk group, there was no significant difference between the low-tension repair group and the high-tension repair group in terms of operation time, thoracic tube drainage time, hospital stay, and long-term survival rate. Group A and group B showed good left ventricular function, while group C showed more decreased left ventricular EF and LVFS (LVEF 54.06 ± 10.28, LVFS 26.94 ± 5.83, p < 0.001). On the comparison of measures of left ventricular size, the mean values of left ventricular end-diastolic diameters(LVDD) and left ventricular end-systolic diameters (LVDS) were significantly difference in group C. Univariate analysis showed that LHR, o/e LHR, operation time, and high-tension repair were the influencing factors of left ventricular dysfunction. Multivariate logistic regression analysis identified risk factors for high-tension repair. Severe left heart dysfunction occurred in 2 patients with ECMO requirement in the high-tension repair group, although the difference was not significant. CONCLUSIONS: High-tension repair is a potential cause of left ventricular dysfunction in neonates with low-risk CDH.

Peritoneal Fluid Analysis of Advanced Ovarian Cancers after Hyperthermic Intraperitoneal Chemotherapy.

This study investigated miRNA and cytokine expression changes in peritoneal fluid samples of patients with advanced ovarian cancer (OVCA) after receiving hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS). We collected samples prior to HIPEC, immediately after HIPEC, and 24/48/72 h after CRS from a total of 6 patients. Cytokine levels were assessed using a multiplex cytokine array, and a miRNA PanelChip Analysis System was used for miRNA detection. Following HIPEC, miR-320a-3p, and miR-663-a were found to be immediately down-regulated but increased after 24 h. Further, significant upregulation post-HIPEC and sustained increases in expression were detected in six other miRNAs, including miR-1290, miR-1972, miR-1254, miR-483-5p, miR-574-3p, and miR-574-5p. We also found significantly increased expression of cytokines, including MCP-1, IL-6, IL-6sR, TIMP-1, RANTES, and G-CSF. The changing expression pattern throughout the study duration included a negative correlation in miR-320a-3p and miR-663-a to cytokines including RANTES, TIMP-1, and IL-6 but a positive correlation in miRNAs to cytokines including MCP-1, IL-6sR, and G-CSF. Our study found miRNAs and cytokines in the peritoneal fluid of OVCA patients demonstrated different expression characteristics following CRS and HIPEC. Both changes in expression demonstrated correlations, but the role of HIPEC remains unknown, prompting the need for research in the future.

Single-direction thoracoscopic lobectomy for children with congenital lung malformation: initial experience.

BACKGROUND: Thoracoscopic lobectomy is a common treatment for congenital lung malformation. Single-direction thoracoscopic lobectomy may be an effective and safe approach without the need to flip the lung over repeatedly, thus minimizing tissue trauma, but its use has not been reported in children. The purpose of this study was to evaluate the safety and efficacy of single-direction thoracoscopic lobectomy in children. METHODS: A total of 91 patients who underwent thoracoscopic lobectomy in our hospital from January 2020 to December 2020 were retrospectively analysed. According to the inclusion criteria, 21 children were identified as the single-direction group. The details of the single-direction thoracoscopic lobectomy technique are described. Another 21 patients who underwent conventional thoracoscopic lobectomy in the same period were matched using the propensity score matching and set as the control group, the clinical outcomes between the two groups were compared. RESULTS: The median age of the patients was 4.72 months (4.72 ± 0.90) with a mean body weight of 7.43 kg (7.43 ± 1.14). There were no significant differences in intraoperative blood loss (P = 0.549), operation time (P = 0.859), length of chest tube drainage (P = 0.102) and length of hospital stay (P = 0.636) between the 2 groups. No patients experienced bronchopleural fistula and conversion to thoracotomy in either group. All patients recovered well without respiratory symptoms or other complications after follow-up of more than 1 year. CONCLUSIONS: Our preliminary experience presented a series of single-direction video-assisted thoracoscopic lobectomy for children with satisfactory perioperative results.

Single-direction thoracoscopic lobectomy for incomplete pulmonary fissure in children with congenital pulmonary airway malformation: initial experience and propensity score-matched analysis.

PURPOSE: To evaluate the safety and efficacy of single-direction lobectomy for congenital pulmonary airway malformation (CPAM), especially with incomplete pulmonary fissure (IPF). METHODS: A total of 279 patients who underwent thoracoscopic lobectomy in our hospital from January 2019 to January 2022 were analyzed. Fifty-nine children were identified as the single-direction group, and the details of the surgical application are described. The degree of pulmonary fissure completeness was quantified intraoperatively. Propensity score matching was conducted and another 59 patients who underwent conventional lobectomy were matched as the control group. RESULTS: The median age of the patients was 4.9 months and the mean body weight was 7.7 kg. For patients with complete pulmonary fissure, there were no statistical differences between two groups in terms of operative time, intraoperative blood loss, length of chest tube, and hospital stay. For patients with IPF, there were statistical differences between the single-direction group and the control group in terms of operative times (89.10 ± 7.97 min vs. 97.41 ± 7.51 min, P < 0.001), intraoperative blood loss (10.86 ± 5.36 mL vs. 14.14 ± 6.56 mL P = 0.042), and postoperative complications (P = 0.035). CONCLUSION: IPF increases the operative difficulty of thoracoscopic lobectomy for CPAM, and the single-direction lobectomy technique is an effective and safe treatment for IPF.

Small-molecule High-throughput Screening Identifies an MEK Inhibitor PD198306 that Enhances Sorafenib Efficacy via MCL-1 and BIM in Hepatocellular Carcinoma Cells.

BACKGROUND: Sorafenib is the most widely used systematic therapy drug for treating unresectable Hepatocellular Carcinoma (HCC) but showed dissatisfactory efficacy in clinical applications. OBJECTIVE: We conducted a combinational quantitative small-molecule high-throughput screening (qHTS) to identify potential candidates to enhance the treatment effectiveness of sorafenib. METHODS: First, using a Hep3B human HCC cell line, 7051 approved drugs and bioactive compounds were screened, then the primary hits were tested with/without 0.5 µM sorafenib respectively, the compound has the half maximal Inhibitory Concentration (IC50) shift value greater than 1.5 was thought to have the synergistic effect with sorafenib. Furthermore, the MEK inhibitor PD198306 was selected for the further mechanistic study. RESULTS: 12 effective compounds were identified, including kinase inhibitors targeting MEK, AURKB, CAMK, ROCK2, BRAF, PI3K, AKT and EGFR, and a µ-opioid receptor agonist and a Ltype calcium channel blocker. The mechanistic research of the combination of sorafenib plus PD198306 showed that the two compounds synergistically inhibited MEK-ERK and mTORC1- 4EBP1 and induced apoptosis in HCC cells, which can be attributed to the transcriptional and posttranslational regulation of MCL-1 and BIM. CONCLUSION: Small-molecule qHTS identifies MEK inhibitor PD1938306 as a potent sorafenib enhancer, together with several novel combination strategies that are valuable for further studies.

(18F)-PSMA-1007PET/CT in patients with biochemical recurrence after radical prostatectomy: Diagnostic performance and impact on treatment management.

Objective: To evaluate the diagnostic performance of (18F)-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy and the effect of (18F)-PSMA-1007 PET/CT on treatment strategy. Methods: A total of 114 patients with BCR after radical prostatectomy who performed (18F)-PSMA-1007 PET/CT were retrospectively analyzed. The Gleason scores (GS), maximum standardized uptake values (SUVmax) and the diagnostic performance were compared according to different prostate-specific antigen (PSA) groups. To evaluate the impact of (18F)-PSMA-1007 PET/CT on treatment management, we also collected subjects' therapy before and after PET/CT. The PSA value was monitored to evaluate the biochemical response. Results: (18F)-PSMA-1007PET/CT was positive in 92/114 patients (80.7%). The detection rates were 20/34 (58.8%), 13/17 (76.5%), 15/17 (88.2%) and 44/46 (95.7%) for PSA levels of 0.2-<0.5, 0.5-<1, 1-<2, ≥2 ng/ml. The positive lesions on PET/CT revealed local recurrence in 24/114 (21.1%) patients, lymph nodes metastases in 54/114 (47.4%) and metastatic sites in bone, lung, and others in 75/114 (65.8%). A significant positive correlation was observed between the GS/ SUVmax and PSA level (r1 = 0.375, r2 = 0.336, P<0.001). As a result of the (18F)-PSMA-1007 PET/CT, therapeutic decision-making changed in 60/114 (52.6%) patients. With a follow-up of 11.0 ± 6.4 months, 81/114 PSA were collected after treatment guided by (18F)-PSMA-1007 PET/CT, and in 42/81 (51.9%) of patients, serum PSA levels decreased of more than 60%. Conclusion: (18F)-PSMA-1007 PET/CT has a high lesion detection rate for recurrent prostate cancer (PCa) and could have significant implications in decision-making treatment plan for the majority of PCa patients.