Case report: EGFR fusion mutation combined with EGFR amplification responds to EGFR-TKI therapy.

Given their good antitumor effects, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-sensitive mutations, including exon 19 deletions and exon 21 L858R mutations. EGFR fusion mutations and EGFR amplification are very rare in non-small cell lung cancer (NSCLC). We describe 2 patients with NSCLC harboring EGFR fusion mutations (EGFR-MACF1 and EGFR-GNAT3) combined with EGFR amplification. Both patients received EGFR-TKI treatment, and 1 of them showed an antitumor response.

Exploration of the Fire-Retardant Potential of Microencapsulated Ammonium Polyphosphate in Epoxy Vitrimer Containing Dynamic Disulfide Bonds.

Epoxy vitrimers appear as a promising alternative to common epoxy thermoset composites. Nevertheless, the possibilities of applying these materials are limited due to their high flammability which may cause high fire risks. To date, the flame-retardant epoxy vitrimer systems reported in the literature almost all rely on intrinsic flame retardancy to achieve high fire safety; however, the complex and expensive synthesis process hinders their large-scale application. In this work, disulfide-based epoxy vitrimer (EPV) was fabricated with 4, 4'-dithiodianiline as the curing agent, and microencapsulated ammonium polyphosphate (MFAPP) was employed as a potential additive flame retardant to improve their fire retardancy. As a comparative study, common epoxy (EP) composites were also prepared using 4,4'-diaminodiphenylmethane as the curing agent. The results showed that the introduction of dynamic disulfide bonds led to a reduction in the initial thermal decomposition temperature of EPV by around 70 °C compared to EP. Moreover, the addition of 7.5 wt.% of MFAPP endowed EP with excellent fire performance: the LOI value was as high as 29.9% and the V-0 rating was achieved in the UL-94 test (3.2 mm). However, under the same loading, although EPV/MFAPP7.5% showed obvious anti-dripping performance, it did not reach any rating in the UL-94 test. The flame-retardant mechanisms in the condensed phase were evaluated using SEM-EDS, XPS, and Raman spectroscopy. The results showed that the residue of EPV/MFAPP7.5% presented numerous holes during burning, which failed to form a continuous and dense char layer as a physical barrier resulting in relatively poor flame retardancy compared to EP/MFAPP7.5%.

Different gastric tubes in esophageal reconstruction during esophagectomy.

Esophagectomy is currently the mainstay of treatment for resectable esophageal carcinoma. Gastric grafts are the first substitutes in esophageal reconstruction. According to the different tailoring methods applied to the stomach, gastric grafts can be classified as whole stomach, subtotal stomach and gastric tube. Gastric-tube placement has been proven to be the preferred method, with advantages in terms of postoperative complications and long-term survival. In recent years, several novel methods involving special-shaped gastric tubes have been proposed, which have further decreased the incidence of perioperative complications. This article will review the progress and clinical application status of different types of gastric grafts from the perspectives of preparation methods, studies of anatomy and perioperative outcomes, existing problems and future outlook.

Delta-radiomics based on CT predicts pathologic complete response in ESCC treated with neoadjuvant immunochemotherapy and surgery.

Background and purpose: Unnecessary surgery can be avoided, and more appropriate treatment plans can be developed for patients if the efficacy of neoadjuvant immunochemotherapy for esophageal cancer (EC) can be predicted before surgery. The purpose of this study was to evaluate the ability of machine learning models based on delta features of immunochemotherapy CT images to predict the efficacy of neoadjuvant immunochemotherapy in patients with esophageal squamous cell carcinoma (ESCC) compared with machine learning models based solely on postimmunochemotherapy CT images. Materials and methods: A total of 95 patients were enrolled in our study and randomly divided into a training group (n = 66) and test group (n = 29). We extracted preimmunochemotherapy radiomics features from preimmunochemotherapy enhanced CT images in the preimmunochemotherapy group (pregroup) and postimmunochemotherapy radiomics features from postimmunochemotherapy enhanced CT images in the postimmunochemotherapy group (postgroup). We then subtracted the preimmunochemotherapy features from the postimmunochemotherapy features and obtained a series of new radiomics features that were included in the delta group. The reduction and screening of radiomics features were carried out by using the Mann-Whitney U test and LASSO regression. Five pairwise machine learning models were established, the performance of which was evaluated by receiver operating characteristic (ROC) curve and decision curve analyses. Results: The radiomics signature of the postgroup was composed of 6 radiomics features; that of the delta-group was composed of 8 radiomics features. The area under the ROC curve (AUC) of the machine learning model with the best efficacy was 0.824 (0.706-0.917) in the postgroup and 0.848 (0.765-0.917) in the delta group. The decision curve showed that our machine learning models had good predictive performance. The delta group performed better than the postgroup for each corresponding machine learning model. Conclusion: We established machine learning models that have good predictive efficacy and can provide certain reference values for clinical treatment decision-making. Our machine learning models based on delta imaging features performed better than those based on single time-stage postimmunochemotherapy imaging features.

Roles of p53-Mediated Host-Virus Interaction in Coronavirus Infection.

The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and the resulting health crisis and economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting the virus on its RNA polymerase, the high mutation rate and unique 3' to 5' exonuclease with proofreading function make it challenging to develop effective anti-coronavirus drugs. As a result, there is an increasing focus on host-virus interactions because coronaviruses trigger stress responses, cell cycle changes, apoptosis, autophagy, and the dysregulation of immune function and inflammation in host cells. The p53 tumor suppressor molecule is a critical regulator of cell signaling pathways, cellular stress responses, DNA repair, and apoptosis. However, viruses can activate or inhibit p53 during viral infections to enhance viral replication and spread. Given its pivotal role in cell physiology, p53 represents a potential target for anti-coronavirus drugs. This review aims to summarize the relationship between p53 and coronaviruses from various perspectives, to shed light on potential targets for antiviral drug development and vaccine design.

Feasibility analysis of combined surgery for esophageal cancer.

BACKGROUND: As the preoperative examination of esophageal cancer has improved, the likelihood of finding diseases in other organs that require surgical treatment has also increased. The purpose of this study was to explore the feasibility of combined surgery for esophageal cancer by analyzing the occurrence of postoperative complications in patients with esophageal cancer. METHODS: The clinical characteristics of 1566 patients with esophageal cancer who underwent thoracic surgery in our hospital between January 2017 and September 2022 were analyzed retrospectively. The feasibility of combined surgery for esophageal cancer was analyzed by comparing postoperative complications in patients who underwent simple esophageal cancer surgery (SEC) with those in patients who underwent combined surgery for esophageal cancer (COEC). The tendency scores of patients in the COEC and SEC groups (1:2) were matched to balance the confounding clinical factors, and the difference in postoperative complications was further analyzed. Moreover, we performed a subgroup analysis of esophagectomy combined with lung resection (ECL). In addition, the independent risk factors for postoperative Clavien-Dindo ≥ grade III complications of esophageal cancer were analyzed by multivariate logistic regression. RESULTS: A total of 1566 patients (1147 (73.2%) males and 419 (26.8%) females), with an average age of 64.2 years, were analyzed. There was no significant difference in postoperative complications between the SEC and COEC groups according to the Clavien-Dindo classification (P=0.713). An analysis of the complications revealed that those in the COEC group had a higher incidence of lung consolidation than those in the SEC group (P=0.007). However, when we performed propensity score matching (PSM) on the SEC and COEC groups, there was still no significant difference in complications according to the Clavien-Dindo classification (P=0.346); furthermore, when a detailed analysis of complications was performed, there was no significant difference between the two. In subgroup analysis, after we performed PSM in ECL patients and SEC patients, we also found no significant difference in postoperative complications between patients with ECL and patients with SEC. In addition, we found that a history of diabetes (OR=1.604, P=0.029, 95% CI=1.049-2.454), a history of coronary heart disease (OR=1.592, P=0.046, 95% CI=1.008-2.515), diffusing capacity of the lungs for carbon monoxide (DLCO) (OR=0.916, P=0.024, 95% CI=0.849-0.988), and ALB level (OR=0.955, P=0.007, 95% CI=0.924-0.987) were independent factors that influenced postoperative complications in esophageal cancer patients with grade III or higher complications. CONCLUSION: Combined surgery for esophageal cancer does not increase the incidence of postoperative complications. In addition, a history of diabetes mellitus or coronary heart disease, carbon monoxide dispersion, and preoperative ALB level are independent risk factors for grade III or higher postoperative complications of esophageal cancer.

Transcriptional Analysis of Tea Plants (Camellia sinensis) in Response to Salicylic Acid Treatment.

Salicylic acid (SA) is an important plant hormone and signal required for establishing resistance to diverse pathogens and plant diseases. The abundant polyphenols in tea plants also defend plants from biotic and abiotic stresses. However, whether exogenous SA would increase the resistance of tea plants to adversity and the relationship between SA and polyphenols are still poorly understood. Here, we carried out SA treatment on tea seedlings and performed transcriptome sequencing. SA treatment inhibited the phenylpropanoid and flavonoid metabolic pathways but promoted the lignin metabolic pathways. The increased accumulation of lignin in tea leaves after treating with SA indicated that lignin might coordinate SA, enhance, and improve plant defense and disease resistance. Simultaneously, an SA-inducible flavonoid glucosyltransferase (CsUGT0554) specifically involved in 7-OH site glycosylation was characterized in vitro. These results provided valuable information about the effects of SA on tea seedlings and the molecular basis for SA-mediated immune responses.

Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation.

Atherosclerosis is a complex pathological process involving macrophages, endothelial cells and vascular smooth muscle cells that can lead to ischemic heart disease; however, the mechanisms underlying cell-to-cell communication in atherosclerosis are poorly understood. In this study, we focused on the role of exosomal miRNAs in crosstalk between macrophages and endothelial cells and explored the rarely studied molecular mechanisms involved. Our in vitro result showed that macrophage-derived exosomal miR-4532 significantly disrupted human umbilical vein endothelial cells (HUVECs) function by targeting SP1 and downstream NF-κB P65 activation. In turn, increased endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and decreased endothelial nitric oxide synthase (eNOS) expression in HUVECs increased attraction of macrophages, exacerbating foam cell formation and transfer of exosomal miR-4532 to HUVECs. MiR-4532 overexpression significantly promoted endothelial injury and pretreatment with an inhibitor of miR-4532 or GW4869 (exosome inhibitor) could reverse this injury. In conclusion, our data reveal that exosomes have a critical role in crosstalk between HUVECs and macrophages. Further, exosomal miR-4532 transferred from macrophages to HUVECs and targeting specificity protein 1 (SP1) may be a novel therapeutic target in patients with atherosclerosis.

Predictive value of modified systemic inflammation score for postoperative unplanned ICU admission in patients with NSCLC.

Background: The purpose of this study was to investigate the predictive value of the modified systemic inflammation score (mSIS) in postoperative unplanned admission to the intensive care unit (ICU) in patients with non-small-cell lung cancer (NSCLC). Methods: The clinical data of 1,321 patients with NSCLC treated with thoracic surgery in our hospital from August 2019 to June 2021 were analyzed retrospectively. The preoperative mSIS, which takes into account the serum albumin (ALB) level and lymphocyte-to-monocyte ratio (LMR), was recorded as 0, 1 or 2 and then was used to identify high-risk patients with unplanned admission to the ICU. The independent risk factors for unplanned admission to the ICU in patients with NSCLC after surgery were identified by multivariate logistic regression analysis. Results: A total of 1,321 patients, including 549 (41.6%) males and 772 (58.4%) females, were included. The median age was 57 years (range 16-95 years). The incidence of unplanned admission to the ICU in patients with mSIS = 2 was significantly higher than that in those with mSIS = 0 and mSIS = 1. The multivariate analysis showed that an mSIS of 2 (OR = 3.728; P = 0.004; 95% CI, 1.520-9.143), an alcohol consumption history (OR = 2.791, P = 0.011; 95% CI, 1.262-6.171), intraoperative infusion volume (OR = 1.001, P = 0.021; 95% CI, 1.000-1.001) and preoperative underlying diseases (OR = 3. 57, P = 0.004; 95% CI, 1.497-8.552) were independent risk factors for unplanned admission to the ICU after lung cancer surgery. In addition, the multivariate logistic regression model showed that the C-statistic value was 0.799 (95% CI: 0.726∼0.872, P < 0.001). Conclusions: The mSIS scoring system can be used as a simplified and effective predictive tool for unplanned ICU admission in patients with NSCLC.

[Retrotransposon insertion polymorphism of the porcine esr gene and its association with production performances of Large White pigs].

Estrogen receptor (esr) mediates the effects of estrogen on the expression of related genes, thereby regulating the growth and reproduction of mammals. To investigate the effect of retrotransposon insertion polymorphism (RIP) of the porcine esr gene on porcine growth performance, retrotransposon insertion polymorphism of the esr gene were predicted by comparative genomics and bioinformatics, and PCR was used to verify the insertion polymorphisms in different porcine breeds. Finally, the correlation analysis between the genotypes and performance of Large White pigs was conducted. The results showed that four retrotransposon polymorphic sites were identified in the esr1 and esr2 genes, which are esr1-SINE- RIP1 located in intron 2 of the esr1 gene, esr1-LINE-RIP2 and RIP3-esr1- SINE located in intron 5 of the gene, and esr2-LINE-RIP located in intron 1 of the esr2 gene, respectively. Among them, insertion of a 287 bp of SINE into intron 2 of the esr1 gene significantly affected (P<0.05) the live back fat thickness and 100 kg body weight back fat thickness of Large White pigs. Moreover, the live back fat thickness and back fat thickness at 100 kg body weight of homozygous with insertion (SINE+/+) was significantly greater than that of heterozygous with insertion (SINE+/-) and homozygous without insertion (SINE-/-). Therefore, esr1-SINE-RIP1 could be used as a molecular marker to assist the selection of deposition traits in Large White pigs.

Asymmetric Sulfoxidation of Thioether Catalyzed by Soybean Pod Shell Peroxidase to Form Enantiopure Sulfoxide in Water-in-Oil Microemulsions: A Kinetic Model.

Esomeprazole with chiral sulfoxides structure is used to treat gastric ulcer disease. Soybean pod shell peroxidase (SPSP) is a peroxidase extracted from soybean pods shells which are one of the most abundant natural resources in the world. In the production of chiral sulfoxides catalyzed by SPSP, it is very important to establish the reaction kinetic model and explore the reaction mechanism for the development of the process, however, there is no report on the establishment of the model. Asymmetric sulfoxidation reactions catalyzed by SPSP in water-in-oil microemulsions were carried out, and the King-Altman approach was used to establish a kinetic model. A yield of 91% and e.e. value of 96% for esomeprazole were obtained at the activity of SPSP of 3200 U ml-1 and 50 °C for 5 h. The mechanism with a two-electron reduction of SPSP-I is accompanied with a single-electron transfer to SPSP-I and nonenzymatic reactions, indicating that three concomitant sub-mechanisms contribute to the asymmetric oxidation involving five enzymatic and two nonenzymatic reactions, which can represent the asymmetric sulfoxidation of organic sulfides to form enantiopure sulfoxides. With 5.44% of the average relative deviation, a kinetic model fitting experimental data was developed. The enzymatic reactions may follow ping-pong mechanism with substrate inhibition of H2 O2 and product inhibition of esomeprazole, while nonenzymatic reactions follow a power law. Those results indicate that SPSP with a lower cost and higher thermal stability may be used as an effective substitute for horseradish peroxidase.

Efficacy of New Zeolite-Based Hemostatic Gauze in a Gunshot Model of Junctional Femoral Artery Hemorrhage in Swine.

BACKGROUND: This work sought to (1) establish a reliable gunshot model of junctional femoral artery rupture in swine that accurately simulates field rescue conditions and (2) use the gunshot model to compare the efficacy and ease of application of zeolite nanometer hemostatic gauze with other hemostatic materials. METHODS: Thirty-six healthy landrace swine (body weight 50 ± 5 kg) were randomly divided into three groups which were treated with Combat Gauze (CG), FeiChuang hemostatic gauze (FG), or standard medical gauze (SG). A gunshot model of femoral artery hemorrhage in landrace swine was used with portable ultrasound to accurately position the wound. After the shooting, when mean arterial pressure of swine decreased by at least 30% for 10 s, wounds were pressed with standard packing (39 g) of gauze materials for 3 min to stop bleeding, then bandaged with pressure. Blood samples were taken 15 min before injury, then 10 min, 30 min, and 60 min after injury to determine hemodynamic, coagulation, and arterial blood gas indexes. Wound temperatures were taken at 5 min, 10 min, 30 min, and 60 min after injury, and survival times were recorded. The volume of blood loss and survival time were used to evaluate hemostatic effect, whereas the fill time, wound temperature, and physiological indexes were used to evaluate the safety and operation of the product. RESULTS: The CG (11.15 ± 3.09 mL/kg) and FG (12.19 ± 3.5 mL/kg) groups had significantly less blood loss than the SG group (16.8 ± 5.14 mL/kg) (P = 0.04; P = 0.039, respectively). After gauze packing, bleeding in CG (5.85 ± 1.17 mL/kg) and FG (5.37 ± 0.93 mL/kg) groups remained significantly lower than that of the SG group (6.93 ± 1.03 mL/kg) (P = 0.011; P = 0.003, respectively). Wound temperature rose with time for all groups (P < 0.001). The wound temperatures in the FG group and the CG group were significantly higher than that of the SG group (P = 004 and 0.009, respectively). Survival rates and times were not significantly different among the three groups, although the FG group had the longest average survival time (standard deviation [SD] 204.8 s), compared with the SG group (SD 177.8 s) and CG (SD 187.5 s) groups. No significant differences in hemodynamics, blood gas, and coagulation were observed among the three groups. CONCLUSIONS: The gunshot model of junctional femoral arterial hemorrhage guided by ultrasound had high accuracy for femoral arterial rupture by bullet wound and provided consistent and reproducible field-simulation conditions for comparison of hemostatic materials. FeiChuang zeolite hemostatic gauze effectively controlled bleeding as well as combat gauze, without excessive heat as found in other zeolite-based products. However, improvements to application technique, such as a packing device, are needed to improve operating time.

[Analysis of diseases distribution in Medical Information Mart for Intensive Care III database].

OBJECTIVE: To study the distribution of diseases in Medical Information Mart for Intensive Care (MIMIC-III) database in order to provide reference for clinicians and engineers who use MIMIC-III database to solve clinical research problems. METHODS: The exploratory data analysis technologies were used to explore the distribution characteristics of diseases and emergencies of patients (excluding newborns) in MIMIC-III database were explored; then, neonatal gestational age, weight, length of hospital stay in intensive care unit (ICU) were analyzed with the same method. RESULTS: In the MIMIC-III database, 46 428 patients were admitted for the first time, and 49 214 ICU records were recorded. There were 26 076 males and 20 352 females; the median age was 60.5 (38.6, 75.6) years, and most patients were between 60 and 80 years old. The first diagnosis in the disease spectrum analysis was firstly ranked by circulatory diseases (32%), followed by injury and poisoning (14%), digestive system disease (8%), tumor (7%), respiratory disease (6%) and so on. Patients with ischemic heart disease accounted for the largest proportion of circulatory disease (42%), the proportion of these patients gradually increased with age of 60-70 years old, then decreased. However, the proportion of patients with cerebrovascular disease declined first and then increased with age, which was the main cause of death of circulatory system disease (ICU mortality was 22.5%). Injury and poisoning patients showed a significant decrease with age. Digestive system diseases were younger than the general population (most people aged between 50 to 60 years), and non-infectious enteritis and colitis were the main causes of death (ICU mortality was 18.3%). Respiratory infections were predominant in infected patients (34%), but circulatory system infections were the main cause of death (ICU mortality was 25.6%). Secondly, in the neonatal care unit, premature infants accounted for the vast majority (82%). As the gestational age increased, the duration of ICU was decreased, and the mortality was decreased. CONCLUSIONS: The diseases distribution of patients can be provided by MIMIC-III database, which helps to grasp the overview of the volume and age distribution of the target patients in advance, and carry out the next step of research. Meanwhile, it points out the important role of exploratory data analysis in electronic health records analysis.

Beagle sciatic nerve regeneration across a 30 mm defect bridged by chitosan/PGA artificial nerve grafts.

Longitudinally oriented microstructures are essential for a nerve scaffold to promote the significant regeneration of injured peripheral axons across nerve gaps. In the current study, we present a novel nerve-guiding collagen-chitosan (CCH) scaffold that facilitated the repair of 30 mm-long sciatic nerve defects in beagles. The CCH scaffolds were observed with a scanning electron microscope. Eighteen beagles were equally divided into CCH group, autograft group and non-graft group. The posture and gait of each dog was recorded at 12 and 24 weeks after surgery. Electrophysiological tests, Fluoro-Gold retrograde tracing test, Histological assessment of gastrocnemius and immunofluorescent staining of nerve regeneration were performed. Our investigation of regenerated sciatic nerves indicated that a CCH scaffold strongly supported directed axon regeneration in a manner similar to that achieved by autologous nerve transplantation. In vivo animal experiments showed that the CCH scaffold achieved nerve regeneration and functional recovery equivalent to that achieved by an autograft but without requiring the exogenous delivery of regenerative agents or cell transplantation. We conclude that CCH nerve guides show great promise as a method for repairing peripheral nerve defects.

Development of adaptive pneumatic tourniquet systems based on minimal inflation pressure for upper limb surgeries.

BACKGROUND: Pneumatic tourniquets are medical devices that occlude blood flow to distal part of extremities and are commonly used in upper limb surgeries to provide a dry, clean and bloodless field. To decrease pressure-related injuries and potential risk of complications subjected to the high inflation pressure of pneumatic tourniquet, minimal inflation pressures are recommended. METHODS: A new occlusion pressure mathematical model for the upper limb was established based on the correlation analysis between several possible influencing parameters and the minimal pneumatic tourniquet pressure at which the peripheral pulse disappeared was recorded using a digital plethysmograph. A prototype of an adaptive pneumatic tourniquet which automatically varies the pressure in the tourniquet cuff according to the above prediction model was developed for the upper limb which used the lowest possible inflation pressure to achieve occlusion. The prototype comprises a blood pressure monitoring module, an inflatable tourniquet cuff, and a pressure relief mechanism to maintain an optimal cuff inflation pressure. Simulation experiments were conducted to verify the function and stability of the designed adaptive pneumatic tourniquet and clinical experiments using volunteers were undertaken to evaluate the performance of the prototype design in achieving adequate haemostasis in the upper limb. RESULTS: Results demonstrated that the mean arterial occlusion pressure was 152.3 ± 16.7 mmHg, obviously below the 250 to 300 mmHg previously recommended (J Bone Joint Surg Br 68:625-628, 1986 and Arthroscopy 11:307-311, 1995). CONCLUSIONS: In conclusion, this adaptive method and apparatus which can provide minimal inflation pressure may be a clinically practical alternative for upper limb surgery performed with pneumatic tourniquets.

Crossed polydactyly type I caused by a point mutation in the GLI3 gene in a large Chinese pedigree.

Polydactyly is one of the most common forms of congenital malformation in humans, and is displayed by 119 disorders. Crossed polydactyly (CP) is defined as the coexistence of preaxial and postaxial polydactyly with a difference in the axes of polydactyly between the hands and feet. In an effort to map the gene responsible for CP, we studied a seven-generation Chinese family of 56 individuals, 28 of whom were affected. A thorough search with highly informative polymorphic markers showed no recombination among the affected members with the markers on chromosome 7p15-q11.23, but no linkage with chromosomes 2q31, 7q36, 13q, and 19p. Mutation analysis showed a substitution mutation of 1927C --> T in exon 12 of the GLI3 gene, which is predicted to pretruncate the GLI3 protein. This mutation has variable phenotypes of polydactyly, indicating that other genetic factors also contribute to the diversity of polydactyly phenotypes. Our results increase the phenotypic spectrum caused by GLI3 mutations and are important for the analysis and understanding of the etiology of these limb malformations.