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Intramuscular injections of progesterone (P4) are common during assisted reproduction, which can cause painful injection area reactions, and the current study was therefore initiated to determine whether P4 was involved in these adverse local effects. Female Sprague-Dawley rats were given daily intramuscular injection of vehicle oil or P4-in-oil with or without dermal administration of ketoprofen (Ket) gel at right biceps femoris muscle of hindlimb for 5 weeks. It was found that rats receiving repeated vehicle oil injections developed nociception-related behaviours together with induration formation and dorsal root ganglion (DRG) damage, indicating that the vehicle oil contributed to the side-effect reactions. Interestingly, P4 injections caused more nociception-related behaviours than those of vehicle oil as reflected by both nociception score and muscle withdrawal threshold evaluations, which were impressively relieved by Ket. In fact, P4 induced higher induration occurrence rate with larger volume that was alleviated by Ket. Further ELISA assays supported that P4 rather than vehicle oil profoundly elevated inflammatory factor levels. Moreover, an extensive upregulation of Na

Background High-throughput next-generation sequencing (HT-NGS) has the potential to detect a large variety of pathogens; however, the application of HT-NGS in lung transplant (LTx) recipients remains limited. We aimed to evaluate the value of HT-NGS for pathogen detection and diagnosis of pulmonary infection during early-stage post-lung transplantation. Methods In this retrospective study, we enrolled 51 LTx recipients who underwent lung transplantation between January 2020 and December 2020. Bronchoalveolar lavage fluid (BALF) samples were collected for the detection of pathogens using both HT-NGS and conventional microbiological testing. The detection of pathogens and diagnostic performance of HT-NGS were compared with that of conventional methods. Results HT-NGS provided a higher positive rate of pathogen detection than conventional microbiological testing (88.24% vs. 76.47%). The most common bacteria detected via HT-NGS during early-stage post-lung transplantation were Enterococcus, Staphylococcus, Pseudomonas and Klebsiella, while all fungi were Candida and all viruses were Herpesvirus. Uncommon pathogens, including Strongyloides, Legionella, and Mycobacterium abscesses were identified by HT-NGS. The sensitivity of HT-NGS for diagnosing pulmonary infection was significantly higher than that of conventional microbiological testing (97.14% vs. 68.57%; P Conclusion HT-NGS is a highly sensitive technique for pathogen detection, which may provide diagnostic advantages, especially in LTx recipients, contributing to the optimization of treatment regimens against pulmonary infection during early-stage post-lung transplantation.

We performed a meta‐analysis to determine cancer risks at multiple sites and their associations with tumor mutation burden (TMB), an index for immunogenicity, in heart or lung transplant recipients. A comprehensive search of PubMed, Web of Science, EMBASE, and Medline was conducted. Random effects models were used to calculate standardized incidence ratios (SIRs) versus the general population and to determine the risks of different cancers. Weighted linear regression (WLR) was used to analyze the associations between the SIRs and TMBs. (PROSPERO CRD42020159599). Data from 21 studies including 116,438 transplant recipients (51,173 heart transplant recipients and 65,265 lung transplant recipients) with a total follow‐up of 601,330.7 person‐years were analyzed. Compared with the general population, heart transplant recipients displayed a 3.13‐fold higher cancer risk [SIR: 3.13; 95% confidence interval (CI): 2.38–4.13; p, Our study demonstrated that both heart and lung transplant recipients displayed a higher risk of certain site‐specific cancers. These findings can provide individualized guidance for clinicians for detection of cancer among heart or lung transplantation recipients. In addition, we provided evidence that increased risks of post‐transplant cancers can be attributed to immunosuppression.

Myeloid cell leukemia-1 (Mcl-1) protein is a family of Bcl-2 (B cell lymphoma 2) rich proteases of the most common increase threshold for genetic aberrations observed in human cancer, including lung, breast, pancreatic, cervical, and ovarian cancers as well as leukemia and lymphoma. Mcl-1 is recognized as an attractive drug target in number of diseases, including cancer. In the present study we surveyed and collected queries compounds from PDB database of Mcl-1 protein and generated pharmacophore-based models adapted to screen the drug-like compounds from FDA approved database. The 206 best lead molecules from pharmacophore-screening were further evaluated by molecular docking, molecular dynamics simulation, MM-GBSA calculation, as well as experimental validation. Two hits, ZINC00601272 and ZINC00002166, showed the best docking scores, which showed a tendency to inhibit cell viability of HL60 and K562 leukemia cells with Mcl-1 expressions. Conclusively, the present study provides structural information of Mcl-1 inhibitors for next generations of cancer therapeutics through computational and experimental validation approach. Communicated by Ramaswamy H. Sarma

The present study aimed to compare the post-lung transplant survival and complications of connective tissue disease (CTD)-related interstitial lung disease (ILD) and/or pulmonary arterial hypertension with idiopathic pulmonary fibrosis (IPF).The clinical data of patients with CTD-ILD or IPF who received lung transplantation between 2015 and 2020 were retrospectively reviewed. Cumulative survival rates after transplantation were estimated using the Kaplan-Meier method.The study included 31 patients with confirmed CTD-ILD and 98 with IPF. Patients with CTD-ILD were significantly younger (53.2 ± 13.7 vs. 62.3 ± 7.2 years, p=0.001) and more likely female (61.3% vs. 7.1%, p0.001) than patients with IPF. No significant difference was noticed in the 1-year and 5-year survival rates between CTD-ILD and IPF patients (1-year, 73.2% vs 71.4%, p=0.76; 5-year, 69.1% vs. 39.5%, p=0.21). The incidence of primary graft dysfunction was significantly higher in CTD-ILD patients (90.3% vs. 70.4%, p=0.03), while there was no significant difference in primary graft dysfunction-related mortality (6.5% vs. 6.1%, p=0.95) between the two groups.There was no significant difference in post-lung transplant survival and complications between CTD-ILD and IPF.

BACKGROUND: It has been reported that tubeless video-assisted thoracoscopic surgery (tubeless-VATS) is feasible and safe for thoracic diseases. Herein, we compared the early outcomes of mediastinal lesion resection between the tubeless and traditional VATS. METHODS: Clinical data of all patients who underwent thoracoscopic mediastinal tumor resection were retrospectively collected. The study involved two groups: tubeless and traditional VATS group. Propensity score matching (PSM) was applied to eliminate the population bias. Intraoperative and postoperative variables were compared among matched cohorts. RESULTS: In total, 43 patients in the tubeless group and 231 patients in the traditional VATS group were included. After 1:1 PSM, baseline characteristics were comparable. Anesthesia time (177.63 vs. 202.53 min; P=0.004) was shorter in tubeless group, while operation time (90.95 vs. 101.47 min; P=0.109) was similar. Overall, the total postoperative morbidity rate was similar in the two groups (15% vs. 12.5%; P=0.556). Specially, 4/43 patients in tubeless VATS group need to be re-put chest tubes postoperatively. A significant lower similar level of visual analogue scale score was observed in tubeless VATS group (1.73±0.48 vs. 3.41±0.87, P

Background The purpose of this study was to uncover preoperative risk factors for extubation failure or re-intubation for patients undergoing lung transplant (LTx). Methods We performed a retrospective case-control study of LTx from our center between January 2017 and March 2019. Demographic and preoperative characteristics were collected for all included patients. Univariable analysis and multivariable logistic regression were used to analyze risk factors of postoperative unsuccessful extubation following LTx. Results Among 107 patients undergoing first LTx investigated, 74 (69.16%) patients who were successfully liberated from mechanical ventilation (MV), and 33 (30.84%) patients who were unsuccessful extubation, which 18 (16.82%) patients suffered from reintubation. associated preoperative factors for unsuccessful extubation following LTx included preoperative extracorporeal membrane oxygenation (ECMO) support [OR =4.631, 95% confidence interval (CI): 1.403-15.286, P=0.012], the preoperative ability of independent expectoration (OR =4.517, 95% CI: 1.498-13.625, P=0.007), the age older than 65-year-old (OR =4.039, 95% CI: 1.154-14.139, P=0.029), and receiving the double lung and heart-LTx (OR =3.390, 95% CI: 0.873-13.162, P=0.078; and OR =16.579, 95% CI: 2.586-106.287, P=0.012, respectively). Further, we investigated the preoperative predicted factors for reintubation. Only the preoperative ECMO remained a significant predictor of re-intubation (OR =4.69, 95% CI: 1.56-15.286, P=0.012). Conclusions Preoperative independent sputum clearance, preoperative ECMO, older than 65-year-old, and double lung or heart-LTx were four independent risk factors for unsuccessful extubation. Moreover, preoperative ECMO was the only independent risk factor for reintubation.

BACKGROUND Early endotracheal extubation in operating room (E-OR) after lung transplantation is rarely reported worldwide. Herein, we aim to explore the feasibility and safety of E-OR after lung transplantation and demonstrate its potential benefits. METHODS This study is a single-center retrospective database analysis of 18 patients. All lung transplantation patients with E-OR attempted between June 2018 and September 2019 were included retrospectively. Perioperative variables, including ischemia time, total blood loss, blood lactic acid, the partial pressure of oxygen, partial pressure of oxygen/fraction of inspiration oxygen ratio, time of semi-open pulmonary artery occlusion clamp, extubation rate, and complications after E-OR, were analyzed. Data were compared using non-parametric tests and expressed as the median or number (percentage). RESULTS Clinical data of 18 patients with E-OR attempted were collected. Overall, 15/18 (83.33%) patients successfully underwent E-OR without reintubation. Reintubation occurred in 3/18 (16.67%) patients; one patient presented with decreased blood oxygen saturation and unconsciousness, while two patients developed hypoxemia and respiratory failure after E-OR. Extracorporeal membrane oxygenation (ECMO) was not used postoperatively. No grade 3 primary graft dysfunction was observed and all eighteen patients were alive 1 year after the transplant. No postoperative hemodialysis and tracheotomy occurred. The median length of stay in the intensive care unit (ICU) for E-OR patients was 120 hours, the median length of postoperative hospital stay was 19 days, and the median hospitalization cost was 35,577 USD. CONCLUSIONS Early endotracheal extubation in operating room was feasible and did not delay postoperative recovery in these 18 lung transplantation recipients.

Acute lung injury (ALI) causes high mortality and lacks any pharmacological intervention. Here, we found that pazopanib ameliorated ALI manifestations and reduced mortality in mouse ALI models and reduced edema in human lung transplantation recipients. Pazopanib inhibits mitogen-activated protein kinase kinase kinase 2 (MAP3K2)–and MAP3K3-mediated phosphorylation of NADPH oxidase 2 subunit p47(phox) at Ser(208) to increase reactive oxygen species (ROS) formation in myeloid cells. Genetic inactivation of MAP3K2 and MAP3K3 in myeloid cells or hematopoietic mutation of p47(phox) Ser(208) to alanine attenuated ALI manifestations and abrogates anti-ALI effects of pazopanib. This myeloid MAP3K2/MAP3K3-p47(phox) pathway acted via paracrine H(2)O(2) to enhance pulmonary vasculature integrity and promote lung epithelial cell survival and proliferation, leading to increased pulmonary barrier function and resistance to ALI. Thus, pazopanib has the potential to be effective for treating ALI.

Understanding the cancer risks in different transplant recipients helps early detection, evaluation, and treatment of post-transplant malignancies. Therefore, we performed a meta-analysis to determine the cancer risks at multiple sites for solid organ transplant recipients and their associations with tumor mutation burden (TMB), which reflects the immunogenicity. A comprehensive search of PubMed, Web of Science, EMBASE, Medline, and Cochrane Library was conducted. Random effects models were used to calculate the standardized incidence ratios (SIRs) versus the general population and determine the risks of different cancers. Linear regression (LR) was used to analyze the association between the SIRs and TMBs. Finally, seventy-two articles met our criteria, involving 2,105,122 solid organ transplant recipients. Compared with the general population, solid organ transplant recipients displayed a 2.68-fold cancer risk (SIR 2.68; 2.48–2.89; P

Background: As the COVID-19 pandemic continues to spread worldwide, there is still no accurate rapid diagnostic test for COVID-19, or monitoring tool for patient’s clinical course. An artificial-intelligence system (CoviDet) was therefore developed and applied on chest computed tomography (CT), to evaluate its application for rapid diagnosis and potential monitoring of COVID-19 patients. Methods: 1,201,074 CT slices from 2527 patients were grouped into 3 main groups: COVID-19 positive group, non-COVID-19 viral pneumonia group and control group. They were used to train and validate CoviDet novel stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. A subset of COVID-19 patients with more than 3 consecutive CT images were selected for training and validation of the auto-segmentation and monitoring algorithm. Findings: CoviDet outperforms radiologists, and can diagnose COVID-19 based on CT alone with sensitivity of 0.93, specificity of 0.95 and AUC of 0.98 (95%CI 0.97-0.99; P

Background: Donor-derived cell free DNA (ddcf DNA) has been reported as a universal noninvasive biomarker for rejection monitoring in heart, kidney, liver, and lung transplantation. Current approaches based on next-generation sequencing for quantification of ddcf DNA, although promising, may be restricted by the requirement for donor material, as donor samples may not be available. Methods: We proposed a novel next-generation sequencing approach without donor-derived material and compared the non-donor-derived approach and the donor-derived approach using simulation testing and 69 clinical specimens. We also evaluated the performance for acute rejection and infection monitoring in lung transplantation. Results: The non-donor-derived approach reached similar efficacy as the donor-derived approach with a significant linear correlation of R2 = 0.98. Subsequent validation in clinical specimens demonstrated significant difference between the acute rejection group (4.83% ± 2.11%, mean ± SD) and the non-rejection group (1.61% ± 0.63%, mean ± SD) (P < 0.0001, Welch’s t test). With the cut-off value of 2.999, our approach had 90.48% sensitivity (95% CI, 69.62% - 98.83%), 100% specificity (95% CI, 91.59% - 100%), and AUC 0.9266 (95% CI, 0.8277 - 1.026). The test also had the ability to simultaneously detect infectious agents, especially cytomegalovirus, as compared with the clinical test. Conclusion: The proposed approach without donor-derived material could potentially be used to monitor acute rejection and infection in lung transplantation and may be applied to other types of solid organ transplantation.

In response to the difficulties and problems in the construction of a water-saving society and the construction of a water-saving society in Ningbo in recent years, with rivers as the main canal, the digital economy water-saving society management model was innovatively proposed, and the evaluation index system for social construction was built in the water-saving society, combined with the connotation of the digital economy, a water-saving society evaluation method was put in Ningbo, and suggestions and countermeasures also referred.

Recently, it has been reported that the microRNA-132(miR-132) is linked with synaptic plasticity and cognitive impairment. The present study investigates that whether miR-132 is altered in circulating blood serum samples of post-stroke cognitive impairment (PSCI) patients.We collected samples from 39 subjects with PSCI, 37 subjects with post-stroke cognitive normality (PSCN), and 38 age-matched controls (AMC) for which ages, gender and education level were matched. MiR-132 was detected using a quantitative real-time PCR (qRT-PCR) method. To test the predictive value of miR-132 for PSCI, prediction capabilities were compared using the receiver operating characteristic (ROC) curves and area under curve (AUC) analysis.The level of miR-132 in PSCI patient serum was significantly elevated compared to that of PSCN and AMC subjects. The ROC curve showed that miR-132 achieved an AUC of 0.961 (p0.0001). Importantly, the miR-132 level was correlated with the Montreal Cognitive Assessment (MoCA) score in PSCI patients.These results indicated that there was a substantial correlation between serum miR-132 expression and post-stroke cognitive functionality, suggesting that miR-132 may be a risk marker for PSCI. Because of the limitations of this study, the results should be treated with caution.

The beautiful piano art originated in the West. Since its spread to China, it has been very popular among the public and gradually popularized and popularized in the evolution of time. As far as the piano education in our country is concerned, it has also matured and improved with the progress of the times. However, the piano teaching in higher education institutions in China today focuses on the western piano music content. The teaching system undertakes the western piano music teaching system, from practice songs to teaching materials and even teaching forms. This will mislead students to produce Chinese piano teaching content. The mentality of attaching importance to the content of western piano teaching may even lead to students’ misperception of the content of Chinese piano teaching. Therefore, integrating folk music into piano teaching in Chinese colleges and universities, using computer technology as an aid, and inheriting and promoting piano art with Chinese characteristics through the network cloud platform has a certain significance of the times. This paper analyzes the current application of folk music in piano teaching in colleges and universities in China under the network cloud platform, and analyzes the causes of the current situation, sums up the necessity of Chinese folk music in the piano teaching of colleges and universities in China and the corresponding good strategies.

In 2016, owing to the growth in e-commerce, over 31 billion of goods have been delivered in Mainland China which is more than 50% volume in 2015. The rapid growth of delivery volume introduces a big challenge to logistics researches. Existing researches focus on single trip routing problems which delivers goods to multiple customersin a single trip and backhauling to the distribution center with no-load. With the huge volume of delivery with time window constraints in every day, multiple backhauling with no-load is time-consuming and greatly increases the transportation cost. So, in this work, we propose an interactive routing model using a mobile storage house to meet delivery vehicles dynamically to reduce the cost of backhauling with no-load under time window constraints. Experimental results show that the proposed method effectively reduces the transportation cost in all cases and enhances customer satisfactory in many cases.

The leakage current, dielectric and loss properties of the integrated Pt/PbTiO3/ PbZr0.3Ti0.7O3/PbTiO3/Pt capacitors have been investigated. The capacitor has a same leakage mechanism as the film, in the low field region (less than 100 kV/cm) is Ohmic-like, and in the high field region (above 100 kV/cm) is Space-charge-limited current with deep traps. It also indicates that the process didn't affect the conduction mechanism in the capacitors, which is still determined by intrinsic character of materials. The dielectric constant of the capacitors is lower than that of the films. The loss of the capacitors is lower than thin film in the low frequency region (less than 500 kHz), and it is larger in the high frequency region (above 500 kHz). The DC voltage dependence of dielectric loss characteristic indicates that the possibility of main loss mechanism is the charge defects. The different properties between the integrated capacitors and films are ascribed to the excess Pb which volatilization is obstructed b...

Well-ordered large-area two-dimensionally (2D) periodic and individually addressable metal–ferroelectric–metal (M/F/M) nanocapacitor arrays were fabricated by focused ion beam (FIB) milling with synchronal and serial mode. Scanning electron microscopy (SEM) results indicated that the synchronal mode can fabricate more uniform arrays than serial mode, but the surface of arrays is damaged heavily. The various gray contrasts of domain images can be clearly observed in the M/F/M arrays, and its piezoresponse signal is larger than that of the F/M arrays. Piezoresponse force microscope (PFM) results also indicate that the ion damage can be reduced by top Pt electrode, but cannot be avoided. The displacement-voltage and P-E loops of the M/F/M nanocapacitor are indicative of strong ferroelectricity for the measurements. The remanent polarization is reduced by ion damage, but the coercive field is not increased comparing to the thin film.

To investigate the quality of life and influence factors in patients awaiting lung transplantation.Fifty five participants who waited for lung transplantation were enrolled and received multiple surveys including Short Form 36 Health Survey Questionnaires (SF-36), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and Perceiving Social Support Scale (PSSS).The subjects awaiting lung transplant scored ranging from (23.18±37.53) to (74.57±26.02) regarding SF-36, significantly lower than norms (p0.01); they scored (48.09±9.06) and ( 52.18±9.98) in SAS and SDS respectively, which were significant higher compared with norms (p0.01), the patients scored (5.56±1.04) regarding social total support factor in PSSS questionnaire, and the scores of family support factor was significantly higher than that of outside family support factor (p0.05). Single factor analysis revealed that the factors affecting quality of life included monthly family per capita income, medical cost source, dyspnea, BMI, anxiety, depression, and social support (p0.05). Multiple factor analysis screened dyspnea (p0.001) and depression (p0.05) as influence factors of quality of life in patients awaiting lung transplantation.Affected by various factors, the quality of life in patients awaiting lung transplant surgery is relatively poor, among which dyspnea and depression are dominant influence factors. Therefore, clinicians should take psychological and physiological measures to effectively enhance the quality of life in patients awaiting lung transplantation.

The domain images of ferroelectric capacitors with different top electrode thicknesses in the as-grown and poled states were obtained by piezoresponse force microscopy (PFM). In poled capacitors, a uniform piezoresponse with the same contrast was obtained for top electrodes of different thicknesses. For capacitors in the as-grown state, a lower piezoresponse was observed with thicker top electrodes, due to the different domain orientations, suppression effect of the ferroelectric domains and the damping effect of the electrode. It is shown that the piezoresponse decreases nonlinearly with the increase in electrode thickness. When the top electrode thickness is above 75 nm, the piezoresponse value is almost zero. When the top electrode thickness is increased from less than 10 to 75 nm, the piezoresponse is reduced rapidly to a very small value. Details of the domain wall, grain boundary and defects gradually become indistinguishable. Our investigation suggests that to obtain clear domain information by PFM based on global excitation, the top electrode thickness should be less than 10 nm.