Endoscopic resection of giant esophageal subepithelial lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Increased reports on endoscopic resection (ER) of esophageal giant subepithelial lesions (g-SELs) have emerged in recent years. The aim of this study was to evaluate the efficacy, technical difficulty, and safety through our single-center experience. METHODS: Seventy-five patients with g-SELs undergoing endoscopic resection were included in the training set. Clinicopathologic features, procedure-related characteristics, postprocedural outcomes, and follow-up data were analyzed. A predictive nomogram model for procedural difficulty was proposed based on the multivariable logistic regression analysis. Internal and external validations were conducted to verify the model performance. RESULTS: The overall en bloc resection rate was 93.3%. Intraoperative and postoperative adverse events occurred in 7 (9.3%) and 13 (17.3%) patients, respectively. No recurrence or metastasis was observed. Thirty-two (42.7%) patients underwent a difficult procedure. Age (adjusted odds ratio [aOR], .915; P = .004), maximal tumor diameter ≥8 cm (aOR, 9.896; P = .009), irregular shape (aOR, 4.081; P = .053), extraluminal growth pattern (aOR, 5.419; P = .011), and submucosal tunneling endoscopic resection (aOR, .109; P = .042) were found to be statistically or clinically significant factors for predicting endoscopic resection difficulty, based on which a nomogram model was developed. Internal and external validations of the nomogram via receiver-operating characteristic curves and calibration curves achieved favorable results. CONCLUSIONS: Endoscopic resection serves as a promising therapeutic option for esophageal g-SELs. A younger patient age, large tumor size, irregular shape, and extraluminal growth may indicate increased endoscopic resection difficulty, whereas a submucosal tunneling endoscopic resection procedure tends to be of lower difficulty. Our nomogram model performs well for predicting endoscopic resection difficulty for esophageal g-SELs.

Mother-reliant or self-reliant: the germination strategy of seeds in a species-rich alpine meadow is associated with the existence of pericarps.

BACKGROUND AND AIMS: Some plants germinate their seeds enclosed by a pericarp, whereas others lack the outer packaging. As a maternal tissue, the pericarp might impart seeds with different germination strategies. Plants in a community with different flowering times might separately disperse and germinate their seeds; therefore, flowering time can be considered as one manifestation of maternal effects on the offspring. The mass of the seed is another important factor influencing germination and represents the intrinsic resource of the seed that supports germination. Using seeds from a species-rich alpine meadow located in the Hengduan Mountains of China, a global biodiversity hotspot, we aimed to illustrate whether and how the type of seed (with or without a pericarp) modulates the interaction of flowering time and seed mass with germination. METHODS: Seeds were germinated in generally favourable conditions, and the speed of germination [estimated by mean germination time (MGT)] was calculated. We quantified the maternal conditions by separation of flowering time for 67 species in the meadow, of which 31 produced seeds with pericarps and 36 yielded seeds without pericarps. We also weighed 100 seeds of each species to assess their mass. KEY RESULTS: The MGT varied between the two types of seeds. For seeds with pericarps, MGT was associated with flowering time but not with seed mass. Plants with earlier flowering times in the meadow exhibited more rapid seed germination. For seeds without a pericarp, the MGT depended on seed mass, with smaller seeds germinating more rapidly than larger seeds. CONCLUSIONS: The distinct responses of germination to flowering time and seed mass observed in seeds with and without a pericarp suggest that germination strategies might be mother-reliant for seeds protected by pericarps but self-reliant for those without such protection. This new finding improves our understanding of seed germination by integrating ecologically mediated maternal conditions and inherent genetic properties.

Feasibility of a novel unassisted single-channel transcolonic endoscopic appendectomy for the treatment of appendiceal lesions (with video).

BACKGROUND: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA. METHOD: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedure­related parameters, and follow­up data and analyzed the impact of previous abdominal surgery and traction technique. RESULTS: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3-15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor. CONCLUSION: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases.

Transfer learning-enabled outcome prediction for guiding CRRT treatment of the pediatric patients with sepsis.

Continuous renal replacement therapy (CRRT) is a life-saving procedure for sepsis but the benefit of CRRT varies and prediction of clinical outcomes is valuable in efficient treatment planning. This study aimed to use machine learning (ML) models trained using MIMIC III data for identifying sepsis patients who would benefit from CRRT. We first selected patients with sepsis and CRRT in the ICU setting and their gender, and an array of routine lab results were included as features to train machine learning models using 30-day mortality as the primary outcome. A total of 4161 patients were included for analysis, among whom there were 1342 deaths within 30 days. Without data augmentation, extreme gradient boosting (XGBoost) showed an accuracy of 64.2% with AUC-ROC of 0.61. Data augmentation using a conditional generative adversarial neural network (c-GAN) resulted in a significantly improved accuracy (82%) and ROC-AUC (0.78%). To enable prediction on pediatric patients, we adopted transfer learning approaches, where the weights of all but the last hidden layer were fixed, followed by fine-tuning of the weights of the last hidden layer using pediatric data of 200 patients as the inputs. A significant improvement was observed using the transfer learning approach (AUCROC = 0.76) compared to direct training on the pediatric cohort (AUCROC = 0.62). Through this transfer-learning-facilitated patient outcome prediction, our study showed that ML can aid in clinical decision-making by predicting patient responses to CRRT for managing pediatric sepsis.

Analysis of the Dynamic Expression of the SMAD Family in the Periosteum During Guided Bone Regeneration.

OBJECTIVE: The aim of this study was to investigate the dynamic expression of the SMAD family during guided bone regeneration for the reconstruction of cranio-maxillofacial bone defects. METHODS: A swine model of guided bone regeneration was established with one side of the rib as the trauma group and the contralateral as control group. Periosteal and regenerative tissue specimens were harvested at 9 time points in the early, middle, and late phases, and were subjected to gene sequencing and tissue staining. Expression data of each SMAD family were extracted for further analysis, in which the correlation of the expression of the respective members within and between groups and at different time points was analyzed. RESULTS: The expression of individual members of the SMAD family fluctuates greatly, especially during the first month. The SMAD3 and SMAD4 genes were the most highly expressed. The foldchange value of SMAD6 was the largest and remained above 1.5 throughout the process. The dynamic expression levels of SMAD2, SMAD4, SMAD5, SMAD6, and SMAD9 showed a significant positive correlation in both groups. The expression levels of each gene showed a positive correlation with other SMAD genes. Tissue staining showed that the overall contour of the regenerated bone tissue was basically formed within the first 1 month. CONCLUSION: The first month of guided bone regeneration is a critical period for bone regeneration and is an important period for the SMAD family to play a role. The SMAD6 may play an important role in the whole process of guided bone regeneration.

FOXF2 oppositely regulates stemness in luminal and basal-like breast cancer cells through the Wnt/beta-catenin pathway.

The stemness of cancer cells contributes to tumorigenesis, the heterogeneity of malignancies, cancer metastasis, and therapeutic resistance. However, the roles and regulatory mechanisms maintaining stemness among breast cancer subtypes remain elusive. Our previous studies have demonstrated that ectopic expression and dynamic alteration of the mesenchymal transcription factor forkhead box F2 (FOXF2) differentially regulates breast cancer progression and metastasis organotropism in a cell subtype-specific manner. Here, we reveal the underlying mechanism by which FOXF2 enhances stemness in luminal breast cancer cells but suppresses that in basal-like breast cancer (BLBC) cells. We show that luminal breast cancer and BLBC cells with FOXF2-regulated stemness exhibit partial mesenchymal stem cell properties that toward osteogenic differentiation and myogenic differentiation, respectively. Furthermore, we show that FOXF2 activates the Wnt signaling pathway in luminal breast cancer cells but represses this pathway in BLBC cells by recruiting nuclear receptor coactivator 3 (NCoA3) and nuclear receptor corepressor 1 (NCoR1) to the promoters of Wnt family member 2B (WNT2B) and frizzled class receptor 1 (FZD1) genes to activate and repress their transcription, respectively. We propose that targeting the Wnt signaling pathway is a promising strategy for the treatment of breast cancers with dysregulated expression of FOXF2.

Whether the Golgi protein 73 could be a diagnostic serological marker in hepatocellular carcinoma: a meta analysis.

BACKGROUND: The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. METHODS: 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. RESULTS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74-0.83),0.85(95%CI 0.80-0.89),5.4(95%CI 3.8-7.5), 0.25(95%CI 0.20-0.31), 22(95%CI 13-35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64-0.81),0.70(95%CI 0.49-0.85),2.40(95%CI 1.3-4.7),0.38(95%CI 0.23-0.61),6(95%CI 2-19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. CONCLUSION: The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Endoscopic submucosal dissection for anastomotic lesions after colorectal surgery.

BACKGROUND: Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the lower gastrointestinal tract. METHOD: We retrospectively investigated 55 patients with anastomotic lesions of the lower gastrointestinal tract who underwent ESD from February 2008 to January 2021. The lesions involving one or both sides of anastomoses were classified into the unilaterally involving anastomosis (UIA) or straddling anastomosis (SA) group, respectively. We collected clinicopathological characteristics, procedure-related parameters and outcomes, and follow-up data and analyzed the impact of anastomotic involvement. RESULTS: The mean age was 62.5 years, and the median procedure duration was 30 min. The rates of en bloc resection and R0 resection were 90.9% and 85.5%, respectively. Four patients (7.3%) experienced major adverse events (AEs). During a median follow-up of 66 months (range 14-169), seven patients had local recurrence, and six patients had metastases. The 5-year disease-free survival and overall survival rates were 82.4% and 90.7%, respectively. The 5-year disease -specific survival (DSS) rate was 93.3%. Compared with the UIA group, the SA group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and R0 resection, and shorter disease-free survival (all P < 0.05). However, rates of AEs did not differ significantly between the two groups. CONCLUSIONS: The short-term and long-term outcomes of ESD for colorectal anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for lesions at the anastomoses.

Endoscopic submucosal dissection for lesions involving the anastomosis after upper gastrointestinal surgery.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging due to severe fibrosis, deformity, staples, and limited space for procedure. We aimed to characterize the clinicopathological characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the upper gastrointestinal tract. METHODS: We retrospectively investigated 43 patients with lesions involving the anastomoses of the upper GI tract who underwent ESD from April 2007 to February 2021. We collected clinicopathological characteristics, procedure­related parameters and outcomes, and follow­up data and analyzed the impact of anastomotic involvement. RESULTS: The median duration from previous upper GI surgery was 60 months and the median procedure duration was 30 min. The rate of en bloc resection and en bloc with R0 resection was 90.7% and 81.4%, respectively. Two patients (4.7%) experienced major adverse events, including delayed bleeding and febrile episode. During a median follow-up of 80 months, 3 patients had local recurrence and 4 patients had metastases. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 89.6% and 95.1%, respectively. Compared with the unilaterally involving group, the straddling anastomosis group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and en bloc with R0 resection, and shorter DFS and OS (all P < 0.05). However, rates of adverse events did not differ significantly between the two groups. CONCLUSIONS: The short­ and long-term outcomes of ESD for upper GI anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for anastomotic lesions.

Global development and future trends of artificial sweetener research based on bibliometrics.

Artificial sweeteners have sparked a heated debate worldwide due to their ambiguous impacts on public and environmental health and food safety and quality. Many studies on artificial sweeteners have been conducted; however, none scientometric studies exist in the field. This study aimed to elaborate on the knowledge creation and development of the field of artificial sweeteners and predict the frontiers of knowledge based on bibliometrics. In particular, this study combined VOSviewer, CiteSpace, and Bibliometrix to visualize the mapping of knowledge production, covered 2389 relevant scientific publications (1945-2022), and systematically analyzed articles and reviews (n = 2101). Scientific publications on artificial sweeteners have been growing at an annual rate of 6.28% and globally attracting 7979 contributors. Susan J. Brown with total publications (TP) of 17, average citation per article (AC) of 36.59, and Hirsch (h)-index of 12 and Robert F. Margolskee (TP = 12; AC = 2046; h-index = 11) were the most influential scholars. This field was clustered into four groups: eco-environment and toxicology, physicochemical mechanisms, public health and risks, and nutrition metabolism. The publications about environmental issues, in particular, "surface water," were most intensive during the last five years (2018-2022). Artificial sweeteners are gaining importance in the monitoring and assessment of environmental and public health. Results of the dual-map overlay showed that the future research frontiers tilt toward molecular biology, immunology, veterinary and animal sciences, and medicine. Findings of this study are conducive to identifying knowledge gaps and future research directions for scholars.

The effect of green channel for stroke patients on treatment of severe aneurysmal subarachnoid hemorrhage.

PURPOSE: To explore the effect of green channel for stroke patients on the treatment of severe aneurysmal subarachnoid hemorrhage. METHODS: This is a retrospective case-control study. The clinical data of patients with severe aneurysmal subarachnoid hemorrhage admitted to the emergency department of our hospital from January 2015 to June 2022 were retrospectively analyzed. Patients diagnosed with subarachnoid hemorrhage, confirmed intracranial aneurysm by preoperative CT angiography or digital subtraction, graded Hunt-Hess grade III, IV, and V, < 72 h from the onset to the time of consultation received surgical treatment in our hospital were included in this study. Patients with serious underlying diseases, such as heart, liver, kidney diseases, or malignant tumors, traumatic subarachnoid hemorrhage, previous history of cerebral hemorrhage, and incomplete data were excluded. The control group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2015 to December 2018 before the establishment of the green channel for stroke patients, and the observation group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2019 to June 2022 after the establishment of the green channel. The control group received routine treatment in the emergency department; the observation group received improved treatment of green channel for stroke patients. Gender, age, Hunt-Hess grade on admission, modified Rankin scale (mRS) on admission, aneurysm location, aneurysm size and whether accompanied by intracerebral hemorrhage, the time from onset to emergency department, the time from emergency department to vascular diagnostic examination, the time from onset to surgery, the time from emergency department to surgery, the time from hospital admission to surgery, length of hospital stay, complications, treatment effect were analyzed and compared between the 2 groups. SPSS 23.0 software was utilized to conduct comparisons between the 2 groups. The t-test, Chi-square test, or Mann-Whitney U test was chosen based on the data type. Statistical significance was established when p < 0.05. RESULTS: A total of 71 patients were included in this study, of whom 37 were in the control group and 34 were in the observation group. There were no statistical differences in age, gender, Hunt-Hess grade, mRS scores, aneurysm location, aneurysm size, intracerebral hemorrhage, the time from onset to emergency department, length of hospital stay, complications between the observation group and the control group (all p > 0.05). The time (min) from visit to vascular diagnostic test (60.50 vs. 120.00, p = 0.027), the time (min) from onset to surgery (1792.00 vs. 2868.00, p = 0.023), the time (min) from emergency department to surgery (1568.50 vs. 2778.00, p = 0.016), the time (min) from hospital admission to surgery (1188.50 vs. 2708.00, p = 0.043), all of them were shorter in the observation group than those in the control group. The relative values of admission and 7-day postoperative mRS scores and the relative values of admission and discharge mRS scores ≥ 2 were used as the criteria for determining better efficacy, and the treatment effect was better than that in the control group, and the differences were statistically significant (admission to 7 days postoperative mRS score ≥ 2, 17 (50.0 %) vs. 8 (21.6 %), p = 0.012; admission to discharge mRS score ≥ 2, 19 (55.9 %) vs. 11 (29.7 %), p = 0.026). CONCLUSION: The green channel for stroke patients with severe aneurysmal subarachnoid hemorrhage can effectively shorten the time from arrival at the emergency department to vascular diagnostic examination and the time from the emergency department to surgery, and achieve a better therapeutic effect, which is worth popularizing and applying.

Transesophageal endoscopic resection of mediastinal cysts (with video).

BACKGROUND AND AIMS: Primary mediastinal cysts are infrequent lesions derived from a variety of mediastinal organs or structures. Complete surgical resection is the treatment of choice even in asymptomatic patients to prevent severe adverse events (AEs) and to establish the diagnosis. Transesophageal endoscopic resection of benign mediastinal tumors has been proven feasible. The aim of this study was to evaluate the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal cysts. METHODS: From January 2016 to May 2021, patients with mediastinal cysts who underwent transesophageal endoscopic resection were retrospectively included. Clinicopathologic characteristics, procedure-related parameters, AEs, and follow-up outcomes were analyzed. RESULTS: Ten patients with mediastinal cysts were included in this study. The mean cyst size was 3.3 ± 1.3 cm. Histopathology revealed 3 bronchogenic cysts (30.0%), 4 esophageal duplication cysts (40.0%), 2 gastroenteric cysts (20.0%), and 1 lymphatic cyst (10.0%). All procedures were performed uneventfully without conversion to traditional surgery. En-bloc resection was achieved in 6 patients (60.0%). Aggressive resection was avoided to prevent damage to the surrounding vital organs. Mean resection time and suture time were 58.0 ± 36.4 minutes and 5.4 ± 1.0 minutes, respectively. No major pneumothorax, bleeding, mucosal injury, or fistula occurred. One patient had a transient febrile episode (>38.5°C). Mean postoperative hospital stay was 2.7 ± .9 days. No residual or recurrent lesions were observed in any patient during a mean follow-up period of 29.8 ± 19.5 months. CONCLUSIONS: Transesophageal endoscopic surgery appears to be a feasible, safe, effective, and much less invasive approach for mediastinal cyst resection. Larger prospective studies are required to fully assess the efficacy and safety of this novel technique.

Perfluorinated compounds (PFCs) in regional industrial rivers: Interactions between pollution flux and eukaryotic community phylosymbiosis.

Perfluorinated compounds (PFCs) pose serious threats to aquatic ecosystems, especially their microbial communities. However, little is known about the phylosymbiosis of aquatic fungal and viridiplantae communities in response to PFC accumulation. We quantified the distribution of 14 PFCs in rivers and found that PFBA was dominant in the transition from water to sediment. High through-put sequencing revealed that phyla Ascomycota, Basidiomycota, Anthophyta, and Chlorophyta were the predominant in eukaryotic community. The effects of PFCs on spatial community coalescence at taxonomic and phylogenetic levels (p < 0.05) were revealed. Fungal community coalescence triggered the spatial assembly of fungal and viridiplantae communities in riverine environments (p < 0.05). Null modeling indicated that PFBA, PFTrDA and PFOS, etc, mediated phylogenetic assembly (p < 0.05) and stochastic processes (86.67-100%) maintain phylogenetic turnover in the fungal community. Meanwhile, variable selection (27.78-54.44%) explained the viridiplantae community assemblage. Finally, we identified fungal genera Hannaella, Naganishia, Purpureocillium and Stachybotrys as indicators for PFC pollution (p < 0.001). These results help explain the effects of PFCs on riverine ecological remediation.

Simazine perturbs the maturational competency of mouse oocyte through inducing oxidative stress and DNA damage.

Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.

[Clinical Study on Early Extubation and Sequential Non-Invasive Respiratory Support for Children with Acute Respiratory Failure Receiving Invasive Mechanical Ventilation].

Objective: To explore the treatment outcome of the strategy of early extubation and then switching to non-invasive mechanical ventilation in children with acute respiratory failure, and the safety and feasibility of using the strategy to replace traditional methods. Methods: A total of 102 children, aged between 1 month to 14 years old, who had acute respiratory failure and were admitted to the pediatric ICU of West China Second University Hospital, Sichuan University between January 2019 and December 2020 were enrolled and randomly assigned to treatment group 1 (n=55) and treatment group 2 (n=47). In addition, 53 children who had the same condition in the 12 month prior to the beginning of the study were included in the control group. In the two treatment groups, the patients were extubated first, and then weaned off the ventilator. In group 1, when the patient met the invasive-non-invasive switching criteria, the tracheal tube was pulled out and non-invasive bi-level positive airway pressure (BiPAP) ventilation was used for respiratory support. In group 2, high-flow nasal cannula (HFNC) oxygen therapy was used for respiratory support. The traditional progressive weaning method was adopted for the control group (extubing and weaning were performed at the same time). The incidence of ventilator-associated pneumonia (VAP) during the period of tracheal intubation was compared and the mortality of the two groups was evaluated from the point when the patients were recruited. At the time of extubation in the treatment groups and extubation plus weaning in the control group, the pressure support levels, or PC above PEEP, intubation time, sequential time (between 2 treatment groups only), weaning failure rate, and the incidence of laryngeal edema and nasal pressure ulcer were compared. Results: The subjects of the study were predominantly infants (93 cases, 60%) and young children (31 cases, 20%). Among the 155 cases, 82 (53%) were male. There was no statistical difference in age distribution or gender among the groups. There was no significant difference in the clinical indicators among the three groups before tracheal intubation. At the time of extubation, the PC above PEEP in the two treatment groups was higher than that in the control group, and higher in group 1 than that of group 2, the difference being statistically significant (P<0.05). The intubation time of the two treatment groups was shorter than that of the control group, and shorter in group 1 than that of group 2 (P<0.05). The sequential time of group 2 was shorter than that of group 1 (P<0.05). The extubation failure rate and the incidence of VAP in the two treatment groups were lower than those in the control group, and there was no statistically significant difference between the two treatment groups. The incidence of nasal pressure ulcers in group 1 was higher than that in the other two groups (P<0.05). There was 1 death in treatment group 1, and no deaths in treatment group 2 or the control group. There was no significant difference in mortality or the incidence of laryngeal edema after extubation in the three groups. Conclusion: Early extubation and then switching to non-invasive mechanical ventilation can be well tolerated by the patients, and can be used in clinical practice as an effective weaning method for children with acute respiratory failure.

[A new isoflavone from Dalbergia odorifera and inhibitory activity of its tyrosinase].

Twelve flavonoids were isolated and purified from the ethyl acetate fraction of 95% ethanol extract of Dalbergia odorifera by heat reflux extraction, solvent extraction, recrystallization, normal phase silica gel, Sephadex LH-20, MCI gel and HPLC methods. The structures were identified with multiple spectroscopic methods, including 1 D-NMR, 2 D-NMR and MS. The compounds were identified as 6,7,8-trimethoxy-5,4'-dihydroxy isoflavone(1), medicarpin(2), 7,2'-dihydroxy-4'-methoxy-isoflavanol(3), biochanin A(4), prunetin(5), genistein(6), pratensein(7), 3-(4-hydroxyphenyl)-6-isopentenyl-7-methoxy-4H-chromen-4-one(8), tectorigenin(9), irisolidone(10), vestitol(11), and formononetin(12). Compound 1 was a new isoflavone, and compound 8 was isolated from D. odorifera for the first time. The results showed that compounds 1-3 had inhibitory effects on tyrosinase, with inhibition rates of 35.58%, 38.63% and 51.34% at the concentration of 1.0 mmol·L~(-1), respectively.

Prevalence and outcomes of re-positive nucleic acid tests in discharged COVID-19 patients.

The prevalence and outcomes of patients who had re-activation of coronavirus disease 2019 (COVID-19) after discharge remain poorly understood. We included 126 consecutively confirmed cases of COVID-19 with 2-month follow-up data after discharge in this retrospective study. The upper respiratory specimen using a reverse-transcription polymerase chain reaction test of three patients (71 years [60-76]) were positive within 11-20 days after their discharge, with an event rate of 19.8 (95%CI 2.60-42.1) per 1,000,000 patient-days. Moreover, all re-positive patients were asymptomatic. Our findings suggest that few recovered patients may still be virus carriers even after reaching the discharge criteria.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

Targeting DNA-PK overcomes acquired resistance to third-generation EGFR-TKI osimertinib in non-small-cell lung cancer.

The third-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), represented by osimertinib, has achieved remarkable clinical outcomes in the treatment of non-small-cell lung cancer (NSCLC) with EGFR mutation. However, resistance eventually emerges in most patients and the underlying molecular mechanisms remain to be fully understood. In this study, we generated an osimertinib-acquired resistant lung cancer model from a NSCLC cell line H1975 harboring EGFR L858R and T790M mutations. We found that the capacity of DNA damage repair was compromised in the osimertinib resistant cells, evidenced by increased levels of γH2AX and higher intensity of the comet tail after withdrawal from cisplatin. Pharmacological inhibiting the activity or genetic knockdown the expression of DNA-PK, a key kinase in DNA damage response (DDR), sensitized the resistant cells to osimertinib. Combination of osimertinib with the DNA-PK inhibitor, PI-103, or NU7441, synergistically suppressed the proliferation of the resistant cells. Mechanistically, we revealed that DNA-PK inhibitor in combination with osimertinib resulted in prolonged DNA damage and cell cycle arrest. These findings shed new light on the mechanisms of osimertinib resistance in the aspect of DNA repair, and provide a rationale for targeting DNA-PK as a therapeutic strategy to overcome osimertinib-acquired resistance in NSCLC.