Selenite selectively kills lung fibroblasts to treat bleomycin-induced pulmonary fibrosis.

BACKGROUND: Interstitial lung disease (ILD) treatment is a critical unmet need. Selenium is an essential trace element for human life and an antioxidant that activates glutathione, but the gap between its necessity and its toxicity is small and requires special attention. Whether selenium can be used in the treatment of ILD remains unclear. METHODS: We investigated the prophylactic and therapeutic effects of selenite, a selenium derivative, in ILD using a murine model of bleomycin-induced idiopathic pulmonary fibrosis (IPF). We further elucidated the underlying mechanism using in vitro cell models and examined their relevance in human tissue specimens. The therapeutic effect of selenite in bleomycin-administered mice was assessed by respiratory function and histochemical changes. Selenite-induced apoptosis and reactive oxygen species (ROS) production in murine lung fibroblasts were measured. RESULTS: Selenite, administered 1 day (inflammation phase) or 8 days (fibrotic phase) after bleomycin, prevented and treated deterioration of lung function and pulmonary fibrosis in mice. Mechanistically, selenite inhibited the proliferation and induced apoptosis of murine lung fibroblasts after bleomycin treatment both in vitro and in vivo. In addition, selenite upregulated glutathione reductase (GR) and thioredoxin reductase (TrxR) in murine lung fibroblasts, but not in lung epithelial cells, upon bleomycin treatment. GR and TrxR inhibition eliminates the therapeutic effects of selenite. Furthermore, we found that GR and TrxR were upregulated in the human lung fibroblasts of IPF patient samples. CONCLUSIONS: Selenite induces ROS production and apoptosis in murine lung fibroblasts through GR and TrxR upregulation, thereby providing a therapeutic effect in bleomycin-induced IPF.

[Effectiveness comparison of ultrasound-guided closed reduction and Kirschner wire fixation for different unstable humeral lateralcondylar fractures of children].

Objective: To compare the effectiveness of ultrasound-guided closed reduction and Kirschner wire fixation for different unstable humeral lateralcondylar fractures of children. Methods: The clinical data of 94 children with unstable humeral lateralcondylar fractures admitted to three medical centers between January 2021 and October 2022 were retrospectively analyzed. The children were divided into three groups according to the Song classification and whether the elbow joint was dislocated or not, including 42 cases of Song 4 type (group A), 38 cases of Song 5 type (group B), and 14 cases of elbow joint dislocation (group C). There was no significant difference in gender, age, side, cause of injury, and time from injury to operation among the three groups ( P>0.05). All children were treated with ultrasound-guided closed reduction and Kirschner wire fixation. The operation time and complications of the three groups were recorded and compared, and the failure of closed reduction was evaluated by ultrasound. X-ray examination was performed at last follow-up to measure the Baumann angle, condylar angle, carrying angle, and lateral osteophyte of the affected side; the extension, flexion, pronation, and supination range of motion of the affected elbow joint were measured; the function of the elbow joint was evaluated by Mayo score. Results: The operation time in group A was significantly longer than that in groups B and C ( P<0.05). There were 7, 2, and 5 cases of closed reduction failure in groups A, B, and C, respectively, and there was no significant difference in the incidence of the closed reduction failure ( P>0.05). All patients were followed up 6-28 months, with an average of 15.7 months. There was no significant difference in the follow-up time among the three groups ( P>0.05). Complications: in group A, there were 2 cases of delayed union, 4 cases of needle tract infection, 1 case of trochlear necrosis, and 39 cases of lateral osteophyte; in group B, there was 1 case of malunion, 5 cases of needle tract infection, 1 case of redisplacement, and 26 cases of lateral osteophyte; in group C, there were 2 cases of needle tract infection and 10 cases of lateral osteophyte. There was no significant difference in the incidence of complications among the three groups ( P>0.05). No cubitus varus or cubitus valgus deformity was found in all patients. At last follow-up, except that the condylar angle in group A was significantly greater than that in groups B and C ( P<0.05), there was no significant difference in other imaging indicators, elbow range of motion, or Mayo score between groups ( P>0.05). Conclusion: The Song type 4 of humeral lateralcondylar fracture treated with ultrasound-guided closed reduction and Kirschner wire fixation has a longer operation time, more postoperative complications, and is more prone to lateral osteophyte.

Criteria of ultrasound-guided closed reduction with percutaneous pinning in unstable humeral lateral condylar fractures: a three-center retrospective cohort study.

Background: Interventions using ultrasound-guided closed reduction and percutaneous pinning (UG-CRPP) of humeral lateral condylar fractures (HLCFs) have been increasingly applied; however, their effectiveness for unstable HLCFs and the criteria for ultrasound outcomes remain unclear. This study assessed the outcomes of UG-CRPP for HLCFs and evaluated the success criteria in children. Methods: Data were retrospectively collected from 106 patients with unstable HLCFs admitted to three hospitals between January 2021 and August 2022. Fifty-five cases were left-sided and 51 cases were right-sided: 74 male patients and 32 female patients were included. Perioperative data, elbow function, complications, and criteria for UG-CRPP were analyzed. Results: The mean rate of UG-CRPP was 88%. The mean surgical time was 54.56 ± 21.07 min, and the mean fluoroscopy frequency was 9.25 ± 2.93 times. At the last follow-up, there were significant differences in elbow flexion between the affected side (135.82° ± 6.92°) and the unaffected side (140.58° ± 5.85°) (p = 0.01). The Mayo score of the affected side was 90.28° ± 4.97°, the Baumann angle was 71.4° ± 5.4°, condylar shaft angle was 39.9° ± 6.4°, and the carrying angle was 8.4° ± 3.6°. Seventy patients presented mild lateral spurs and 16 patients exhibited moderate spurs. Fourteen patients presented with pin infection, and one patient exhibited postoperative re-displacement. There was no premature physeal closure, varus, or valgus elbow deformity, delayed union, or non-union. Successful ultrasound-based outcome criteria for UG-CRPP were defined as follows: (i) absent or less than a cartilage thickness step on the cartilage hinge on coronal plane parallel articular surface scanning, (ii) no lateral displacement and intact distal end of the condylar and capitellum on coronal plane vertical articular surface scanning, (iii) no anteroposterior displacement and absent or less than a cartilage thickness step on sagittal plane vertical articular surface scanning, and (iv) intact posterior fracture line or less than a cortex step on posterolateral sagittal plane vertical articular surface scanning. Conclusion: UG-CRPP is a procedure with minimal blood loss, less invasive, cosmetic, and no radiation exposure. It yielded good outcomes in unstable HLCFs. The successful criteria make it suitable for clinical application.

Ex Vivo Evaluation of Combination Immunotherapy Using Tumor-Microenvironment-on-Chip.

Combination immunotherapy has emerged as a promising strategy to address the challenges associated with immune checkpoint inhibitor (ICI) therapy in breast cancer. The efficacy of combination immunotherapy hinges upon the intricate and dynamic nature of the tumor microenvironment (TME), characterized by cellular heterogeneity and molecular gradients. However, current methodologies for drug screening often fail to accurately replicate these complex conditions, resulting in limited predictive capacity for treatment outcomes. Here, a tumor-microenvironment-on-chip (TMoC), integrating a circulation system and ex vivo tissue culture with physiological oxygen and nutrient gradients, is described. This platform enables spatial infiltration of cytotoxic CD8+ T cells and their targeted attack on the tumor, while preserving the high complexity and heterogeneity of the TME. The TMoC is employed to assess the synergistic effect of five targeted therapy drugs and five chemotherapy drugs in combination with immunotherapy, demonstrating strong concordance between chip and animal model responses. The TMoC holds significant potential for advancing drug development and guiding clinical decision-making, as it offers valuable insights into the complex dynamics of the TME.

Modified Kirschner wire percutaneous rotation prying reduction combined with elastic stable intramedullary nailing in children with Judet IV radial neck fracture.

PURPOSE: This study was to investigate the feasibility and treatment effect of using modified Kirschner wire (K-wire) percutaneous rotation prying reduction combined with Elastic Stable Intramedullary Nailing (ESIN) in children with Judet IV radial neck fracture. METHODS: A retrospective analysis was conducted on 47 children with Judet IV radial neck fracture who underwent treatment with modified K-wire percutaneous rotation prying reduction combined with ESIN from April 2019 to November 2022, including 25 males and 22 females, with an average age of 8.79 years old (ranging from 5 to 14). The study recorded the surgical time, fluoroscopy time, reduction time, and reduction quality evaluated according to the Metaizeau radiological standard. During the last follow-up, the flexion-extension and forearm rotation function of the affected and healthy sides were recorded, and the Mayo Elbow Performance index was used to evaluate the elbow joint function. RESULTS: The average duration of the operation was 25.51 min (ranging from 14 to 43 min), with a mode of 2 reset times (ranging from 1 to 5) and 8 fluoroscopic times (ranging from 4 to 15). Based on the Metaizeau radiological standard for assessing reduction quality, 45 cases were deemed excellent, while 2 cases were considered good. Following 3-4 weeks of postoperative long-arm cast immobilization, exercises were performed to promote elbow joint and forearm rotation. The ESIN was removed after satisfactory fracture healing around 4 months postoperatively. The average follow-up period was 26.79 months (ranging from 5 to 48). At the final follow-up, the range of motion for the affected limb in flexion, extension, pronation, and supination was (140.23 ± 4.80)°, (4.43 ± 3.98)°, (84.09 ± 4.97)°, and (83.83 ± 4.55)°, respectively. There was no statistically significant difference compared to the healthy side, which had a range of motion of (141.36 ± 3.27)°, (5.28 ± 2.25)°, (85.66 ± 3.20)°, and (84.98 ± 2.57)° (P > 0.05). According to the Mayo Elbow Performance index, 44 cases were rated as excellent and 1 case was considered good. CONCLUSION: The modified K-wire percutaneous rotation prying reduction combined with ESIN is an effective treatment for severe radial neck fractures in children. This technique offers several advantages, including the ability to easily "capture" significantly displaced radial heads, achieve rapid and accurate reduction, and reduce radiation exposure.

[Computer-simulated osteotomy based on health-side combined with guide plate technique in treatment of cubitus varus deformity in adolescents].

Objective: To explore the feasibility and early effectiveness of computer-simulated osteotomy based on the health-side combined with guide plate technique in the treatment of cubitus varus deformity in adolescents. Methods: The clinical data of 23 patients with cubitus varus deformity who met the selection criteria between June 2019 and February 2023 were retrospectively analyzed. There were 17 males and 6 females, ranging in age from 4 to 16 years with an average of 8.5 years. The time from injury to operation was 1-4 years. The angle of distal humerus rotation was defined by humeral head posterior inclination angle using low radiation dose CT to scan the patient's upper extremity data at one time, and the preoperative rotation of the distal humerus on the affected side was (33.82±4.39)°. The CT plain scan data were imported into 9yuan3D digital orthopaedic system (V3.34 software) to reconstruct three-dimensional images of both upper extremities. The simulated operation was performed with the healthy upper extremity as the reference, the best osteotomy scheme was planned, overlapped and compared, and the osteotomy guide plate was prepared. The patients were followed up regularly after operation, and the formation of callus in the osteotomy area was observed by X-ray examination. Before and after operation, the carrying angle of both upper extremities (the angle of cubitus valgus was positive, and the angle of cubitus varus was negative) and anteversion angle were measured on X-ray and CT images. At the same time, the flexion and extension range of motion of elbow joint and the external rotation range of motion of upper extremity were measured, and Mayo score was used to evaluate the function of elbow joint. Results: The operation time ranged from 34 to 46 minutes, with an average of 39 minutes. All patients were followed up 5-26 months, with a mean of 14.9 months. All the incisions healed by first intention after the operation; 2 patients had nail path irritation symptoms after Kirschner wire fixation, which improved after dressing change; no complication such as breakage and loosening of internal fixators occurred after regular X-ray review. Continuous callus formed at the osteotomy end at 4 weeks after operation, and the osteotomy end healed at 8-12 weeks after operation. At last follow-up, the carrying angle, anteversion angle, external rotation range of motion, and extension and flexion range of motion of the elbow joint of the affected side significantly improved when compared with preoperative ones ( P<0.05). Except for the extension range of motion of the healthy elbow joint ( P<0.05), there was no significant difference in other indicators between the two sides ( P>0.05). At last follow-up, the Mayo elbow score was 85-100, with an average of 99.3; 22 cases were excellent, 1 case was good, and the excellent and good rate was 100%. Conclusion: Computer-simulated osteotomy based on health-side combined with guide plate technique for treating cubitus varus deformity in adolescents can achieve precise osteotomy, which has the advantages of short operation time and easy operation, and the short-term effectiveness is satisfactory.

Dynamic QTL mapping revealed primarily the genetic structure of photosynthetic traits in castor (Ricinus communis L.).

High photosynthetic efficiency is the basis of high biomass and high harvest index in castor (Ricinus communis L.). Understanding the genetic law of photosynthetic traits will facilitate the breeding for high photosynthetic efficiency. In this study, the dynamic QTL mapping was performed with the populations F2 and BC1 derived from 2 parents with significant difference in net photosynthetic rate (Pn) at 3 stages, in order to reveal the genetic structure of photosynthetic traits. In F2 population, 26 single-locus QTLs were identified, including 3/3/1 (the QTL number at stage I/II/III, the same below), 1/2/0, 1/2/2, 1/3/1, 0/1/1, and 1/1/2 QTLs conferring Pn, water use efficiency (Wue), transpiration rate (Tr), stomatal conductance (Gs), intercellular CO2 concentration (Ci) and chlorophyll content (Cc), with a phenotypic variation explained (PVE) of 8.40%/8.91%/6.17%, 5.36%/31.74%/0, 7.31%/12.80%/15.15%, 1.60%/6.44%/0.02%, 0/1.10%/0.70% and 2.77%/3.96%/6.50% respectively. And 53 epistatic QTLs (31 pairs) were identified, including 2/2/5, 5/6/3, 4/4/2, 6/3/2, 3/2/0 and 4/0/0 ones conferring the above 6 traits, with a PVE of 6.52%/6.47%/19.04%, 16.72%/15.67%/14.12%, 18.57%/15.58%/7.34%, 21.72%/8.52%/7.13%, 13.33%/4.94%/0 and 7.84%/0/0 respectively. The QTL mapping results in BC1 population were consistent with those in F2 population, except fewer QTLs detected. Most QTLs identified were minor-effect ones, only a few were main-effect ones (PVE > 10%), focused on 2 traits, Wue and Tr, such as qWue1.1, qWue1.2, FqTr1.1, FqTr6, BqWue1.1 and BqTr3; The epistatic effects, especially those related to the dominance effects were the main genetic component of photosynthetic traits, and all the epistatic QTLs had no single-locus effects except qPn1.2, FqGs1.2, FqCi1.2 and qCc3.2; The detected QTLs underlying each trait varied at different stages except stable QTLs qGs1.1, detected at 3 stages, qWue2, qTr1.2 and qCc3.2, detected at 2 stages; 6 co-located QTLs were identified, each of which conferring 2-5 different traits, demonstrated the gene pleiotropy between photosynthetic traits; 2 QTL clusters, located within the marker intervals RCM1842-RCM1335 and RCM523-RCM83, contained 15/5 (F2/BC1) and 4/4 (F2/BC1) QTLs conferring multiple traits, including co-located QTLs and main-effect QTLs. The above results provided new insights into the genetic structure of photosynthetic traits and important references for the high photosynthetic efficiency breeding in castor plant.

Long-Term Maternal and Child Outcomes Following Postnatal SSRI Treatment.

Importance: Although selective serotonin reuptake inhibitors (SSRIs) are recommended for postnatal depression treatment, there is a lack of evidence regarding long-term maternal and child outcomes following postnatal SSRI treatment. Objective: To examine whether postnatal SSRI treatment moderated postnatal depression-associated maternal and child outcomes across early childhood years. Design, Setting, and Participants: This cohort study used longitudinal data from the Norwegian Mother, Father and Child Cohort Study. Participating women were recruited in weeks 17 to 18 of pregnancy from 1999 to 2008 and were prospectively followed up after childbirth. Data analysis was performed between December 2021 to October 2022. Exposure: Postnatal depression diagnosis (a binary indicator of eligibility for treatment) was defined as a score of 7 or greater on the 6-item version of the Edinburgh Postnatal Depression Scale. The Hopkins Symptom Checklist was used as a continuous indicator of and postnatal depressive symptomology at postpartum month 6. Postnatal SSRI treatment was identified using self-reported data at postpartum month 6. Main Outcomes and Measures: Maternal outcomes included self-reported depression symptomology and relationship satisfaction from childbirth to postpartum year 5. Child outcomes included maternal-report internalizing and externalizing problems, attention-deficit/hyperactivity disorder symptoms, and motor and language development at ages 1.5, 3, and 5 years. A propensity score adjustment method was used to control for prenatal factors associated with postnatal SSRI exposure probability. Results: Among a total of 61 081 mother-child dyads, 8671 (14.2%) (mean [SD] age, 29.93 [4.76] years) met the criteria for postnatal depression diagnosis, 177 (2.0%) (mean [SD] age, 30.20 [5.01] years) of whom received postnatal SSRI treatment. More severe postnatal depression symptomology was associated with a range of adverse maternal and child outcomes. Focusing analyses only on the postnatal depression dyads indicated that postnatal SSRI treatment attenuated negative associations between postnatal depression and maternal relationship satisfaction at postpartum month 6 (moderation ß, 0.13; 95% CI, 0.07-0.19), years 1.5 (moderation ß, 0.11; 95% CI, 0.05-0.18) and 3 (moderation ß, 0.12; 95% CI, 0.04-0.19), and for child ADHD at age 5 years (moderation ß, -0.15; 95% CI, -0.24 to -0.05). Postnatal SSRI treatment mitigated the negative associations between postnatal depression and maternal depression, partner relationship satisfaction, child externalizing problems, and attention-deficit/hyperactivity disorder up to 5 years after childbirth. Conclusions and Relevance: The results of this large prospective cohort study suggest that postnatal SSRI treatment was associated with a reduced risk of postnatal depression-associated maternal mental health problems and child externalizing behaviors across early childhood years. These findings suggest that postnatal SSRI treatment may bring benefits in the long term to women with postnatal depression and their offspring. This study potentially provides valuable information for clinicians and women with postnatal depression to make informed treatment decisions.

Ultrasound, a new adjuvant method for treating acute Monteggia fracture in children.

PURPOSE: This study aims to evaluate the feasibility of using ultrasound-guided Kirschner wire or elastic intramedullary nail for fixation in the treatment of acute Monteggia fracture in children. METHODS: A retrospective analysis was conducted on 31 cases of acute Monteggia fracture in children treated with ultrasound-guided Kirschner wire or elastic intramedullary nail fixation between April 2020 and December 2022, including 14 cases of Kirschner wire fixation and 17 cases of elastic intramedullary nail fixation. During the operation, soft tissue compression and nerve and vascular injuries were explored, fracture reduction was performed under ultrasound guidance, and operation time was recorded. After the operation, X-ray examination was conducted to assess the quality of fracture reduction. At the last follow-up, the flexion, extension, pronation, and supination angles of both affected and unaffected elbow joints were measured, and the Mayo score was used to evaluate elbow joint function. RESULTS: The average duration of surgery was 50.16 ± 19.21 min (ranging from 20 to 100 min). Based on the evaluation criteria for assessing reduction quality, 28 cases were deemed excellent, while 3 cases were considered good. After immobilization with long-arm cast for 4-6 weeks postoperatively, elbow and forearm rotation exercises were performed. Kirschner wires were removed after an average of 6.64 ± 0.93 weeks (ranging from 6 to 9 weeks) postoperatively, and elastic intramedullary nails were removed after an average of 5.12 ± 1.54 months (ranging from 4 to 10 months) postoperatively. The average follow-up time was 19.13 ± 11.22 months (ranging from 4 to 36 months). During the final follow-up, the affected limb's range of motion in flexion, extension, pronation, and supination was (141.16 ± 4.24)°, (4.61 ± 2.81)°, (84.52 ± 3.74)°, and (84.23 ± 3.69)°, respectively. There was no notable variance when compared to the healthy limb, which had a range of motion of (141.81 ± 2.99)°, (4.81 ± 2.50)°, (85.61 ± 3.12)°, and (85.03 ± 2.73)° (P > 0.05). The Mayo Elbow Performance index classified 29 cases as excellent and 2 cases as good. CONCLUSION: Ultrasound-guided Kirschner wire or elastic intramedullary nail fixation can be used for the treatment of acute Monteggia fracture in children, which can explore the surrounding nerves, blood vessels, and soft tissue compression, reduce the difficulty of reduction, and cause minimal trauma. It can greatly reduce the risk of radiation exposure and complications such as vascular and nerve injury during the operation.

Development of unigene-derived SSR markers from RNA-seq data of Uraria lagopodioides (Fabaceae) and their application in the genus Uraria Desv. (Fabaceae).

BACKGROUND: Uraria Desv. belongs to the tribe Desmodieae (Fabaceae), a group of legume plants, some of which have medicinal properties. However, due to a lack of genomic information, the interspecific relationships, genetic diversity, population genetics, and identification of functional genes within Uraria species are still unclear. RESULTS: Using RNA-Seq, a total of 66,026 Uraria lagopodioides unigenes with a total sequence content of 52,171,904 bp were obtained via de novo assembly and annotated using GO, KEGG, and KOG databases. 17,740 SSRs were identified from a set of 66,026 unigenes. Cross-species amplification showed that 54 out of 150 potential unigene-derived SSRs were transferable in Uraria, of which 19 polymorphic SSRs were developed. Cluster analysis based on polymorphisms successfully distinguished seven Uraria species and revealed their interspecific relationships. Seventeen samples of seven Uraria species were clustered into two monophyletic clades, and phylogenetic relationships of Uraria species based on unigene-derived SSRs were consistent with classifications based on morphological characteristics. CONCLUSIONS: Unigenes annotated in the present study will provide new insights into the functional genomics of Uraria species. Meanwhile, the unigene-derived SSR markers developed here will be invaluable for assessing the genetic diversity and evolutionary history of Uraria and relatives.

Cytotoxic T-lymphocyte antigen 4 polymorphisms and breast cancer susceptibility: Evidence from a meta-analysis.

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an immune checkpoint and regulates the immune function of T cells. However, previous findings regarding the association of CTLA-4 polymorphisms and breast cancer remain inconclusive. Therefore, we performed a meta-analysis to investigate the potential effects of five polymorphisms (-1722 T/C, -1661 A/G -318 C/T, +49 A/G, and CT60 A/G) in the CTLA-4 gene on breast cancer susceptibility. METHODS: Relevant literatures were systematically searched through electronic databases including PubMed, EMBASE, and Web of Science up to October 10, 2021. Available data were extracted and odds ratios (ORs) with 95% confidence intervals were used to estimate the pooling effect size. The Newcastle-Ottawa Scale was applied for assessing the quality of included studies. We conducted subgroup analyses based on ethnicity and control sources to explore levels of heterogeneity. Moreover, sensitivity analysis and publication bias were assessed. RESULTS: Finally, a total of 12 eligible studies regarding CTLA-4 polymorphisms and breast cancer were included. For overall analyses, only the +49 A/G polymorphism was significantly associated with breast cancer under allelic (OR = 1.19), dominant (OR = 1.27), and recessive (OR = 1.27) models. Ethnicity-based subgroup analysis found that the +49 A/G polymorphism has a significant risk (OR = 2.03) of breast cancer under the recessive model in the non-Asian population. Studies with hospital-based controls showed that the +49 A/G polymorphism has significant breast cancer risks under allelic (OR = 1.44), dominant (OR = 1.86), and recessive (OR = 1.60) models. In addition, those with population-based controls found that -1722 T/C polymorphism has a significant breast cancer risk under allelic (OR = 1.19) and dominant (OR = 1.26) models. CONCLUSION: This meta-analysis suggested that CTLA-4 + 49 A/G polymorphism may significantly associate with breast cancer susceptibility. Future studies containing various populations are helpful for evaluating the impacts of CTLA-4 polymorphisms on breast cancer susceptibility.

Large-Scale Single-Nucleus RNA Sequencing Compatible with Complex Archived Samples.

Transcriptome profiling at single-cell resolution allows us to identify and assess functional cell types and cellular states, including those within degenerating ocular tissues in retinitis pigmentosa. The technology is particularly valuable when studying tissues with high cellular heterogeneity, or when specific cell types are of interest. In this chapter, we introduce a detailed protocol of a medium-throughput single-nucleus RNA sequencing technique that utilizes frozen tissue as input sample. This protocol can be executed by any researcher with basic training in molecular biology techniques. With this protocol, a single experimenter can easily process two samples per day up to cDNA amplification, and library preparations can be done in batches of 8. Routinely we can obtain ~20 K nuclei per eye from 3 to 4 library preparations.

Glutathione peroxidase 4 expression predicts poor overall survival in patients with resected lung adenocarcinoma.

This study aimed to evaluate the protein expression of glutathione peroxidase 4 (GPX4) in resected non-small cell lung cancer (NSCLC). The clinical relevance and prognostic significance of GPX4 expression were analyzed. We reviewed patients with resected NSCLCs at Taipei Veterans General Hospital between September 2002 and January 2018. Available paraffin-embedded specimens were retrieved for immunohistochemistry (IHC) staining to detect GPX4 expression. The cutoff value for defining GPX4 positivity was determined according to the percentage of tumor stained in the microscopic field. The correlation between immune expression, clinicopathologic data, overall survival (OS), and disease-free survival (DFS) were analyzed. A total of 265 NSCLC specimens were retrieved for IHC staining. GPX4 expression positive was in 192 (72.5%) according to a cutoff value of 5%. GPX4 was a significant prognostic factor for OS and DFS on multivariate analysis at both 5% and 25% cutoff values. GPX4 expression was associated with poor OS and DFS, especially in lung adenocarcinoma (p = 0.008, and 0.027, respectively). In conclusions, IHC analysis revealed that GPX4 expression was associated with poor survival outcomes in patients with resected lung adenocarcinoma. Further research is needed to understand the role of GPX4 in tumorigenesis and the underlying mechanism responsible for survival outcomes in patients with resected lung adenocarcinoma.

Methodology established for the detection of circulating tumor DNA by hybridization capture.

Roche's AVENIO ctDNA analysis kits and bioinformatics analysis (the AVENIO system) are accessible to all NGS laboratories. We have developed an approach, namely the Sec-Seq system, and compared the accuracy, sensitivity, repeatability and economic cost between the AVENIO system and the Sec-Seq system. Both methods share the comparable accuracy and sensitivity in detecting the variant allele frequency of 0.0005, while the Sec-Seq system shows better accuracy in detecting the variant allele frequency of 0.001. Furthermore, the Sec-Seq system displays a much better detection sensitivity than the AVENIO system. The Sec-Seq system has satisfactory performance in detecting the rare genetic variants in ctDNA with lower economic cost compared with the AVENIO system.

Transient Heat Transfer Characteristics in a Flat Plate Heat Sink with Mini-Channels for Cooling High Heat Flux IGBT.

Effective cooling of a high heat flux IGBT electronic system is highly related to system efficiency and safety. A flat plate heat sink was designed to experimentally investigate the transient heat transfer characteristics of IGBT cooling. It is made of aluminum with 20 mini-channels of 249 mm × 3 mm × 4 mm dimensions, which were manufactured by milling machines and melt inert gas (MIG) welding technology to ensure no deformation. Experiments were conducted using deionized water at atmospheric pressure with flow rates of 3.2-9.5 L/min and heat fluxes of 104-347 W/cm2. It was found that instantaneous start-stop and transient heating power variation might cause IGBT failure, especially under low Reynolds and Nusselt number conditions. The temperature rise rate and cooling rate vary with different system parameters. Heating rate can be reduced by high flow rate due to local subcooled boiling. The concept of respond time (RT) based on the piecewise function is suggested to evaluate the influence of transient condition on heating rate. Analysis of flow fluctuation indicated that it would not be a threat to the system except for in extreme cases. These findings provide a reference for the considerations of the design and manufacture of IGBT cooling flat plate heat sinks with mini-channels.

Drainless thoracoscopic surgery should be avoided in primary spontaneous pneumothorax with pleural adhesion.

OBJECTIVES: Drainless thoracoscopic surgery, defined by omitting chest drain after surgery, has been demonstrated to be feasible in selected patients for pulmonary resection. However, drainless procedure for the treatment of primary spontaneous pneumothorax has raised concerns for its safety and thus has been less often reported. We aimed to share our preliminary experience regarding how to select patients with spontaneous pneumothorax for this procedure. METHODS: A retrospective study recruiting 303 consecutive patients with the diagnosis of spontaneous pneumothorax undergoing thoracoscopic surgery in our centre from August 2016 to June 2020 was done. After careful selection, the chest drain was omitted in selected patients who underwent non-intubated uniportal thoracoscopic surgery. Patients' clinical characteristics and perioperative outcomes were analysed. RESULTS: A total of 34 patients underwent drainless thoracoscopic surgery for the treatment of spontaneous pneumothorax. Pleural adhesion was noted in 9 patients during surgery, and all of them (100%) developed residual pneumothorax, among which intercostal drainage was required in 2 (22.2%) patients and ipsilateral pneumothorax recurred 3 years after surgery in 1 (11.1%) patient. Among the remaining 25 without pleural adhesion, 17 (68.0%) developed minor residual pneumothorax (P = 0.006), which all resolved spontaneously within 1-2 weeks, with no complications or recurrence during postoperative follow-up for at least 2 years. CONCLUSIONS: Drainless thoracoscopic surgery for the treatment of primary spontaneous pneumothorax is feasible but can be risky without careful patient selection. In our experience, the drainless procedure should be avoided in patients with identifiable pleural adhesion noted during surgery.

Low temperature hybrid 3D printing of hierarchically porous bone tissue engineering scaffolds within situdelivery of osteogenic peptide and mesenchymal stem cells.

Compared to other conventional scaffold fabrication techniques, three-dimensional (3D) printing is advantageous in producing bone tissue engineering scaffolds with customized shape, tailored pore size/porosity, required mechanical properties and even desirable biomolecule delivery capability. However, for scaffolds with a large volume, it is highly difficult to get seeded cells to migrate to the central region of the scaffolds, resulting in an inhomogeneous cell distribution and therefore lowering the bone forming ability. To overcome this major obstacle, in this study, cell-laden bone tissue engineering scaffolds consisting of osteogenic peptide (OP) loadedß-tricalcium phosphate (TCP)/poly(lactic-co-glycolic acid) (PLGA) (OP/TCP/PLGA, designated as OTP) nanocomposite struts and rat bone marrow derived mesenchymal stem cell (rBMSC)-laden gelatin/GelMA hydrogel rods were produced through 'dual-nozzle' low temperature hybrid 3D printing. The cell-laden scaffolds exhibited a bi-phasic structure and had a mechanical modulus of about 19.6 MPa, which was similar to that of human cancellous bone. OP can be released from the hybrid scaffolds in a sustained manner and achieved a cumulative release level of about 78% after 24 d. rBMSCs encapsulated in the hydrogel rods exhibited a cell viability of about 87.4% right after low temperature hybrid 3D printing and could be released from the hydrogel rods to achieve cell anchorage on the surface of adjacent OTP struts. The OP released from OTP struts enhanced rBMSCs proliferation. Compared to rBMSC-laden hybrid scaffolds without OP incorporation, the rBMSC-laden hybrid scaffolds incorporated with OP significantly up-regulated osteogenic differentiation of rBMSCs by showing a higher level of alkaline phosphatase expression and calcium deposition. This 'proof-of-concept' study has provided a facile method to form cell-laden bone tissue engineering scaffolds with not only required mechanical strength, biomimetic structure and sustained biomolecule release profile but also excellent cell delivery capability with uniform cell distribution, which can improve the bone forming ability in the body.

Endoscopic Screening for Second Primary Tumors of the Esophagus Among Head and Neck Cancer Patients.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol's chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs.

Molecular target therapeutics of EGF-TKI and downstream signaling pathways in non-small cell lung cancers.

Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.

Factors Associated with Nodal Upstaging in Clinical T1a-bN0M0 Non-Small Cell Lung Cancers.

Nodal upstaging of lung adenocarcinoma occurs when unexpected pathological lymph node metastasis is found after surgical intervention, and may be associated with a worse prognosis. In this study, we aimed to determine the predictive factors of nodal upstaging in cT1a-bN0M0 primary lung adenocarcinoma. We retrospectively reviewed a prospective database (January 2011 to May 2017) at National Taiwan University Hospital and identified patients with cT1a-bN0M0 (solid part tumor diameter ≤ 2 cm) lung adenocarcinoma who underwent video-assisted thoracoscopic lobectomy. Logistic regression models and survival analysis were used to examine and compare the predictive factors of nodal upstaging. A total of 352 patients were included. Among them, 28 (7.8%) patients had nodal upstaging. Abnormal preoperative serum carcinoembryonic antigen (CEA) levels, solid part tumor diameter ≥ 1.3 cm, and consolidation-tumor (C/T) ratio ≥ 0.50 on chest computed tomography (CT) were significant predictive factors associated with nodal upstaging, and patients with nodal upstaging tended to have worse survival. Standard lobectomy is recommended for patients with these predictive factors. If neither of the predictive factors are positive, a less invasive procedure may be a reasonable alternative. Further studies are needed to verify these data.