SNP alleviates mitochondrial homeostasis dysregulation-mediated developmental toxicity in diabetic zebrafish larvae.

The incidence of diabetes is increasing annually, and the disease is uncurable due to its complex pathogenesis. Therefore, understanding diabetes pathogenesis and developing new treatments are crucial. This study showed that the NO donor SNP (8 µM) significantly alleviated high glucose-induced developmental toxicity in zebrafish larvae. High glucose levels caused hyperglycemia, leading to oxidative stress and mitochondrial damage from excessive ROS accumulation. This promoted mitochondrial-dependent apoptosis and lipid peroxidation (LPO)-induced ferroptosis, along with immune inflammatory reactions that decreased mitochondrial function and altered intracellular grid morphology, causing imbalanced kinetics and autophagy. After SNP treatment, zebrafish larvae showed improved developmental toxicity and glucose utilization, reduced ROS accumulation, and increased antioxidant activity. The NO-sGC-cGMP signaling pathway, inhibited by high glucose, was significantly activated by SNP, improving mitochondrial homeostasis, increasing mitochondrial count, and enhancing mitochondrial function. It's worth noting that apoptosis, ferroptosis and immune inflammation were effectively alleviated. In summary, SNP improved high glucose-induced developmental toxicity by activating the NO-sGC-cGMP signaling pathway to reduce toxic effects such as apoptosis, ferroptosis and inflammation resulting from mitochondrial homeostasis imbalance.

Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice.

BACKGROUND: Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated. METHODS: The animal model was established for two batches. In the first batch of experiments, Adult C57BL/6J mice were randomly divided into control group and LPS (5 mg/kg, i.p.)group . In the second batch of experiments, mice were randomly divided into control group, LPS group, and LPS+VX765(10 mg/kg, i.p., an inhibitor of NLRP3 inflammasome) group. After 24 hours, mice were anesthetized with isoflurane, blood and intestinal tissue were collected for tissue immunohistochemistry, Western blot analysis and ELISA assays. RESULTS: The C57BL/6J mice injected with LPS for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1ß, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 could reverse these effects induced by LPS. These results indicated that the increased level of IL-1ß and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. In the second batch of experiments, results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection. CONCLUSIONS: In this study, we revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.

Application of the patient-reported outcome-based postoperative symptom management model in lung cancer: a multicenter randomized controlled trial protocol.

INTRODUCTION: Lung cancer is the most common cancer in China, with the highest mortality rate. Surgery is the primary treatment for early lung cancer. However, patients with lung cancer have a heavy burden of symptoms within 3 months after surgery, which seriously affects their quality of life (QOL). The symptom management model based on the patient-reported outcome (PRO) is considered the best caregiving model. The clinical evidence about the symptom management of lung cancer within 3 months after the operation is very limited. Herein, we propose a randomized controlled trial to evaluate the PRO score-based monitoring and alert system for follow-up on psychological and physiological symptoms of lung cancer patients within 3 months after surgery and further investigate the effect of intervention measures based on this PRO score-based system. METHODS AND ANALYSIS: This multicenter, open-label, randomized, parallel superiority trial will be conducted at four hospitals in China. A total of 440 lung cancer patients will be recruited in this study, who will be randomly assigned to the intervention group or the control group in a ratio of 1:1. Any of the target symptoms reaches the preset threshold (score ≥ 4), the patients will accept the symptom management advices based on the PRO. The patients in the control group will follow the current standard procedure of symptom management. The symptom management system is an electronic management system based on WeChat mini programs. All patients will be evaluated for symptoms through the lung cancer module of the MDASI lung cancer-specific scale on the day before surgery, days 1, 3, 5, and 7 after surgery, and once a week during the 12-week post-discharge period. Simultaneously, the EORTC QLQ-C30 scale will be used to evaluate patients' quality of life at baseline and the fourth and twelfth week after the surgery. The mean number of symptom threshold events of the intervention and the control groups were compared by t-test, and the changes of PRO were compared by a mixed effect model. The primary endpoint has been set as the 12-week post-discharge period. DISCUSSION: This study will test the feasibility of the symptom management system based on the mobile social media applet in postoperative caregiving and the efficacy of psychiatrist-assisted treatment and provide evidence in managing the symptoms of patients in the medium and long term. TRIALS REGISTRATION: Trials registration number: ChiCTR 2200058876, Registered 18 April 2022.

The Interleukin-33/ST2 Axis Enhances Lung-Resident CD14+ Monocyte Function in Patients with Non-Small Cell Lung Cancer.

Interleukin-33 (IL-33) binds to its cognate receptor suppression of tumorigenicity 2 (ST2), leading to critical modulatory roles in immune responses during inflammation and cancers. The aim of this study was to investigate the role of IL-33/ST2 signaling in monocyte function in non-small cell lung cancer (NSCLC). Sixty-two NSCLC patients and nineteen controls were enrolled. IL-33 levels and ST2 expression were measured in peripheral blood and bronchoalveolar lavage fluid (BALF) by ELISA and flow cytometry. HLA-DR expression by CD14+ monocytes, granzyme B and proinflammatory cytokine secretion were also investigated in lipopolysaccharide-stimulated cells. CD14+ monocytes purified from BALF in the tumor site were stimulated with IL-33 in vitro, and co-cultured with a lung cancer cell line A549 cells. The cytotoxicity of monocytes with IL-33 stimulation was then assessed. IL-33 levels were lower in the peripheral blood and tumor microenvironment of NSCLC patients. There was no significant difference in peripheral ST2 expression between NSCLC patients and controls. Soluble ST2 levels were increased but membrane-bound ST2 expression in CD14+ monocytes was decreased in tumor microenvironment of NSCLC patients. There were no remarkable differences in either HLA-DR expression or proinflammatory cytokine secretion by circulating CD14+ monocytes between NSCLC patients and controls. CD14+ monocytes in the tumor microenvironment revealed a dysfunctional phenotype, which presented as lower HLA-DR expression and reduced granzyme B and proinflammatory cytokines. A higher concentration of IL-33 stimulation promoted tumor-resident CD14+ monocyte-induced target cell death. The present study indicates that IL-33/ST2 signaling pathway might enhance the activity of tumor-resident CD14+ monocytes in NSCLC.

Corrigendum: Potential clinical impact of metagenomic next-generation sequencing of plasma for cervical spine injury with sepsis in ICU: A retrospective study.

[This corrects the article DOI: 10.3389/fcimb.2022.948602.].

Potential clinical impact of metagenomic next-generation sequencing of plasma for cervical spine injury with sepsis in intensive care unit: A retrospective study.

Cervical spine injury (CSI) accounts for significant mortality in the intensive care unit (ICU), whereas sepsis remains one of the major causes of death in patients with CSI. However, there is no effective method to diagnose sepsis timely. The aim of this study is to investigate the effect of metagenomic next-generation sequencing (mNGS) on the pathogen features and the prognostic prediction of CSI patients with sepsis. A total of 27 blood samples from 17 included patients were tested by mNGS. Data of mNGS were compared with the conventional culture method. The Kaplan-Meier plots were used to visualize survival curves. A Cox proportional hazards model was used to identify independent prognostic factors for survival. Results showed that mNGS detected a wide spectrum of pathogens in CSI patients with sepsis, including 129 bacterial species, 8 viral species, and 51 fungal species. mNGS indicated 85.2% positive results, while the conventional culture method only showed 11.1% positive results in the blood samples. Further analyses revealed that mNGS had no prognostic effect on the septic CSI patients in ICU, whereas positive results of blood culture were closely correlated with an increased hazard ratio (HR) (HR 77.7067, 95%CI 2.860-2641.4595, p = 0.0155). Our results suggested that the mNGS application may provide evidence for clinicians to use antibiotics when a CSI case is diagnosed with sepsis.

Verification of Information Thermodynamics in a Trapped Ion System.

Information thermodynamics has developed rapidly over past years, and the trapped ions, as a controllable quantum system, have demonstrated feasibility to experimentally verify the theoretical predictions in the information thermodynamics. Here, we address some representative theories of information thermodynamics, such as the quantum Landauer principle, information equality based on the two-point measurement, information-theoretical bound of irreversibility, and speed limit restrained by the entropy production of system, and review their experimental demonstration in the trapped ion system. In these schemes, the typical physical processes, such as the entropy flow, energy transfer, and information flow, build the connection between thermodynamic processes and information variation. We then elucidate the concrete quantum control strategies to simulate these processes by using quantum operators and the decay paths in the trapped-ion system. Based on them, some significantly dynamical processes in the trapped ion system to realize the newly proposed information-thermodynamic models is reviewed. Although only some latest experimental results of information thermodynamics with a single trapped-ion quantum system are reviewed here, we expect to find more exploration in the future with more ions involved in the experimental systems.

Prospect and hybridization of three-channel multi-mirror robot for early lung cancer diagnosis and treatment / 中国胸心血管外科临床杂志

@#Nowadays, the development of the medical instrument industry makes rapid changes in clinical practice. Hybridization of latest technology is playing an increasingly important role in the diagnosis and treatment of disease. Especially, the trend of the integration of three-channel hybrid technology in diagnosis and treatment of early lung cancer has become increasingly obvious. This paper will focus on the technical advance of the three-channel multi- mirror robot and its application in the diagnosis and treatment of early lung cancer.

The status of medical physics in radiotherapy in China.

PURPOSE: To present an overview of the status of medical physics in radiotherapy in China, including facilities and devices, occupation, education, research, etc. MATERIALS AND METHODS: The information about medical physics in clinics was obtained from the 9-th nationwide survey conducted by the China Society for Radiation Oncology in 2019. The data of medical physics in education and research was collected from the publications of the official and professional organizations. RESULTS: By 2019, there were 1463 hospitals or institutes registered to practice radiotherapy and the number of accelerators per million population was 1.5. There were 4172 medical physicists working in clinics of radiation oncology. The ratio between the numbers of radiation oncologists and medical physicists is 3.51. Approximately, 95% of medical physicists have an undergraduate or graduate degrees in nuclear physics and biomedical engineering. 86% of medical physicists have certificates issued by the Chinese Society of Medical Physics. There has been a fast growth of publications by authors from mainland of China in the top international medical physics and radiotherapy journals since 2018. CONCLUSIONS: Demand for medical physicists in radiotherapy increased quickly in the past decade. The distribution of radiotherapy facilities in China became more balanced. High quality continuing education and training programs for medical physicists are deficient in most areas. The role of medical physicists in the clinic has not been clearly defined and their contributions have not been fully recognized by the community.

Variation of Chromosome Composition in a Full-Sib Population Derived From 2x × 3x Interploidy Cross of Populus.

Interploidy cross commonly results in complex chromosome number and structural variations. In our previous study, a progeny with segregated ploidy levels was produced by an interploidy cross between diploid female parent Populus tomentosa × Populus bolleana clone TB03 and triploid male parent Populus alba × Populus berolinensis 'Yinzhong'. However, the chromosome compositions of aneuploid genotypes in the progeny were still unclear. In the present study, a microsatellite DNA allele counting-peak ratios (MAC-PR) method was employed to analyze allelic configurations of each genotype to clarify their chromosome compositions, while 45S rDNA fluorescence in situ hybridization (FISH) analysis was used to reveal the mechanism of chromosome number variation. Based on the MAC-PR analysis of 47 polymorphic simple sequence repeat (SSR) markers distributed across all 19 chromosomes of Populus, both chromosomal number and structural variations were detected for the progeny. In the progeny, 26 hypo-triploids, 1 hyper-triploid, 16 hypo-tetraploids, 10 tetraploids, and 5 hyper-tetraploids were found. A total of 13 putative structural variation events (duplications and/or deletions) were detected in 12 genotypes, involved in chromosomes 3, 6, 7, 14, 15, 16, and 18. The 46.2% (six events) structural variation events occurred on chromosome 6, suggesting that there probably is a chromosome breakpoint near the SSR loci of chromosome 6. Based on calculation of the allelic information, the transmission of paternal heterozygosity in the hypo-triploids, hyper-triploid, hypo-tetraploids, tetraploids, and hyper-tetraploids were 0.748, 0.887, 0.830, 0.833, and 0.836, respectively, indicating that the viable pollen gains of the male parent 'Yinzhong' were able to transmit high heterozygosity to progeny. Furthermore, 45S rDNA-FISH analysis showed that specific-chromosome segregation feature during meiosis and chromosome appointment in normal and fused daughter nuclei of telophase II of 'Yinzhong,' which explained that the formation of aneuploids and tetraploids in the progeny could be attributed to imbalanced meiotic chromosomal segregation and division restitution of 'Yinzhong,' The data of chromosomal composition and structural variation of each aneuploid in the full-sib progeny of TB03 × 'Yinzhong' lays a foundation for analyzing mechanisms of trait variation relying on chromosome or gene dosages in Populus.

Research progress of robotic bronchoscopy system and prospect of the combination with artificial intelligence / 中国胸心血管外科临床杂志

@#The robotic bronchoscopy system is a new technology for lung lesion location, biopsy and interventional therapy. Its safety and effectiveness have been clinically proven. Based on many advanced technologies carried by the robotic bronchoscopy system, it is more intelligent, convenient and stable when clinicians perform bronchoscopy operations. It has higher accuracy and diagnostic rates, and less complications than bronchoscopy with the assistance of magnetic navigation and ordinary bronchoscopy. This article gave a review of the progress of robotic bronchoscopy systems, and a prospect of the combination with artificial intelligence.

BIX-01294 inhibits the proliferation of esophageal squamous cell carcinoma cells by inducing DNA damage and activating the mitochondrial apoptosis pathway / 中国胸心血管外科临床杂志

@#Objective    To explore the effects and molecular mechanisms of histone methylase G9a inhibitor BIX-01294 on apoptosis in esophageal squamous cell carcinoma (ESCC). Methods    MTT assay and Colony-forming Units were adopted to determine the effects of BIX-01294 on the growth and proliferation of ESCC cell lines EC109 and KYSE150. Flow cytometry was used to analyze the apoptosis status of ESCC cells after the treatment of BIX-01294. The effects of BIX-01294 treatment on the expressions of G9a catalytic product H3K9me2, DNA double-strand break (DSB) markers, and apoptosis-related proteins were detected by Western blotting. Results    BIX-01294 inhibited the growth of EC109 and KYSE150 cells in a dose-dependent manner (P<0.05), and BIX-01294 with the inhibitory concentration 50%(IC50) significantly inhibited the formation of colony (P<0.05). After 24 hours treatment of BIX-01294 (IC50), the apoptosis rate of EC109 cells increased from 11.5%±2.1% to 42.5%±5.4%, and KYSE150 cells from 7.5%±0.9% to 49.2%±5.2%(P<0.05). The expression level of the G9a catalytic product, H3K9me2, significantly decreased (P<0.05); while the expression of the DSB marker γH2AX was dramatically enhanced (P<0.05). We also found that the mitochondrial apoptosis pathway was activated and the expression levels of cleaved caspase3 and cleaved PARP were significantly elevated (P<0.05). Conclusion    BIX-01294, the inhibitor of methyltransferase G9a, prompted apoptosis in ESCC cells by inducing DSB damage and activating mitochondrial apoptosis pathway.

Development of a robust reporter gene-based assay for the bioactivity determination of recombinant human follicle stimulating hormone (rhFSH) pharmaceutical products.

FSH plays a key role in the function of the reproductive system of human beings and is widely used both diagnostically and therapeutically in reproductive medicine. With the growing incidence of infertility, the demand for FSH pharmaceutical products is increasing. For this reason, the quality control process for FSH products is becoming more stringent. An accurate determination of bioactivity is crucial for the safety and efficacy of recombinant human follicle stimulating hormone (rhFSH). Up to now, in-vivo bioassay based on FSH-induced increases in rat ovarian weight has been the only method widely accepted by different pharmacopoeias. However this method has such drawbacks as the complex procedures, long assay period and high variability. Here, we established a reporter gene assay (RGA) based on the CHO-K1-FSHR-CRE-Luc cell line that stably expresses human follicle stimulating hormone receptor (hFSHR), as well as a luciferase reporter under the control of cyclic adenosine monophosphate (cAMP) response elements (CRES). Our study showed that our new assay not only has good dose-dependent responsiveness to rhFSH, but it also performs excellently in terms of specificity, precision, linearity, and simplicity compared with in-vivo rat bioassays. These results implied that this robust reporter gene assay may be a viable supplement to the animal in-vivo bioassay and may be employed in potency determination of rhFSH pharmaceutical products.

Study on the Application of A New Type of Anhydrous Thoracic Negative Pressure Drainage Device in Patients after Thoracic Surgery / 中国肺癌杂志

BACKGROUND@#After general thoracic surgery, a chest tube is usually placed for closed drainage to expel gas accumulation in the thoracic cavity and fluid accumulation to promote lung re-expansion. It can also be observed whether there is active bleeding after the operation and whether there is a pulmonary leak. The conventional drainage of the chest cavity is connected with a water-sealed drainage bottle, and the patient condition is judged by observing the drainage situation and the fluctuation of the water column, which is a very classic method. However, the water-sealed bottle has the disadvantages of being easy to overturn and inconvenient to carry, which is not conducive to the early activities of patients. Under the concept of accelerated rehabilitation, our center applied a new type of anhydrous thorax negative pressure drainage device and achieved good results. The purpose of this study was to observe the effect of a new type of anhydrous thoracic negative pressure drainage device in patients after thoracic surgery.@*METHODS@#Retrospective analysis of patients who underwent lung surgery in the First Affiliated Hospital of Zhejiang University Medical College from January 2018 to December 2019, patients were divided into two groups. One group of patients used a traditional closed-chest drainage water-sealed bottle as a control group, and the other group used a new type of anhydrous negative-pressure drainage bottle as an experimental group. Patients' gender, age, hypertension, diabetes, smoking history, surgical incisions and surgical methods, and the length of hospital stay and postoperative hospital stay were calculated.@*RESULTS@#There were no statistical differences in age, gender, comorbidities (hypertension, diabetes, smoking history), scope of surgery, and duration of surgery between the two groups of patients, but there were statistical differences in surgical incisions between the two groups of patients (P=0.01). We found that patients using the new waterless negative pressure drainage device were shorter than patients with water negative pressure drainage device in terms of postoperative hospital stay and total hospitalization time, and the difference was statistically significant (P=0.02, P=0.04).@*CONCLUSIONS@#The new type of anhydrous thoracic negative pressure drainage device has a good effect on the rapid recovery and advancement after thoracic surgery.

Predictors for the Bronchiolitis Obliterans Syndrome in Lung Transplant Patient / 中国肺癌杂志

Lung transplantation is the ultimate treatment of end-stage lung disease. After transplantation, the 1-year survival rate is 80%, while the 5-year survival rates remaines at around 50% mainly due to bronchiolitis obliterans syndrome (BOS). BOS is regarded as a fibrosing process in the small airways leading to irreversible airway obstruction. A lot of factors are involved in the development of BOS, such as Ischemia/reperfusion injury, infections, oxidative stress, and acute rejection, etc. Studies have shown that early diagnosis of BOS may improve outcome. It is valuable for the long-term survival of lung transplantation to find out several predictors for the BOS. This article reviews the current state of knowledge on predictors for BOS.

Clinical Evaluation of Absorbable Regenerated Oxidized Cellulose in Lung Cancer Surgery / 中国肺癌杂志

BACKGROUND@#Thoracoscopic safe and effective hemostasis is an important condition for rapid rehabilitation of thoracic surgery. Placing hemostatic materials during surgery is a commonly used method in lung cancer laparoscopic surgery. Among them, resorbable oxidized cellulose is a commonly used hemostatic material. This research aims to observe the hemostatic effect of resorbable oxidized cellulose in lung cancer surgery.@*METHODS@#A retrospective analysis of 42 patients with thoracoscopic lung cancer undergoing radical surgery in the Department of Thoracic Surgery, First Affiliated Hospital of Zhejiang University School of Medicine from July 1, 2018 to December 1, 2018, and intraoperative use of regenerative oxidized cellulose to stop bleeding The clinical and pathological data were selected and the perioperative indicators were selected as the outcome events for statistical analysis.@*RESULTS@#The mean operative time was (120.5±57.3) min. The mean intraoperative blood loss was (26.8±21.6) mL. The average postoperative drainage volume was (513.6±359.5) mL. The average postoperative chest tube indwelling time was (2.6±1.2) d.@*CONCLUSIONS@#The use of absorbable regenerated oxidized cellulose in the radical operation of thoracoscopic lung cancer has a good hemostasis effect, and is suitable for hemostasis of wounds after lymph node dissection.

Prognostic Risk Factors for Patients Receiving Airway Stent Placement / 中国肺癌杂志

BACKGROUND@#Airway stents are used to treat central airway stenosis or tracheal fistula caused by a variety of malignant and benign tracheal diseases as well as iatrogenic procedures. Airway stent placement has a satisfying effect in instantly relieving of symptoms, but the long-term survival of patients still depends on the individualized treatment of the primary diseases. Therefore, exploring the prognostic risk factors of patients who received airway stent placement can be beneficial to the optimization of the placement procedure and also the improvement of individualized clinical management of patients.@*METHODS@#Data of a total of 66 patients who underwent airway stent placement at the First Affiliated Hospital of Zhejiang University from January 2014 to June 2017 were retrospectively collected. Prognostic effects of the clinical characteristics as age, gender, Charlson comorbidity index (CCI) and procedure duration were analyzed.@*RESULTS@#Age and gender had no significant effect on the outcomes of the patients, while higher CCI (P=0.045) and procedure duration over 60 min (P=0.037) were both independent risk factors of poor prognosis. A prognostic nomogram was then constructed, of which the area under the curve of the receiver operating characteristic (ROC) curve and the concordance index (C-index) was 0.71 and 0.69, respectively.@*CONCLUSIONS@#For patients receiving airway stent placement, the baseline CCI and the procedure duration had prognostic significance in clinical practice.

Clinical Comparison of Airway Stent Placement in Intervention Room and Operating Room / 中国肺癌杂志

BACKGROUND@#Airway stent placement is the effective regimen for central airway obstruction (CAO), while its application scenarios varied. This study aimed to make clinical comparison of airway stent placement in the intervention room and operating room.@*METHODS@#Patients underwent airway stent placement between 2014 and 2018 were included in this retrospective case-control study. Clinical performance of airway stent placement in intervention room and operating room were compared.@*RESULTS@#82 patients were included in this study, including 39 in the intervention room and 43 in the operating room. Patients treated in the intervention room had lower Charlson comorbidity index (CCI) (P=0.018) and received less Y-shaped stents (P<0.001). Better clinical response (P=0.026), more stents placed (P<0.001) and longer length of stent (P<0.001) were observed in operating room, while there was no significantly statistical difference of stent-related complications and post-stent survival rate between the two groups. Extracorporeal membrane oxygenation (ECMO) supported airway stent placement procedures were performed in the operating room, which provided definitive safety support for high-risk intervention.@*CONCLUSIONS@#Patients with CAO could benefit from the operating room scenario, and airway stent placement in the operating room is more suitable for patients with higher CCI scores and receiving more complicated procedures.

Advances of Electromagnetic Navigation Bronchoscopy for Peripheral Pulmonary Lesions / 中国肺癌杂志

The incidence of peripheral pulmonary lesions (PPLs) is growing following the adoption of lung cancer screening by low-dose chest CT. The diagnosis and treatment of pulmonary nodules is one of the most difficult problems. Based on the electromagnetic positioning technology, the electromagnetic navigation bronchoscope is guided to the pulmonary nodules for biopsy or treatment, providing a new minimally invasive diagnosis and treatment method for suspicious lung lesions. This paper provides an overview of the current status and progress of electromagnetic navigation bronchoscopy in the diagnosis and treatment of peripheral pulmonary diseases.