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Abstract The development of intracerebral hemorrhage (ICH) is a dynamic process and intervention during the acute phase of ICH is critical for subsequent recovery. Therefore, it is crucial to screen potential signature genes and therapeutic target genes in the acute phase of ICH. In this study, based on the results of mRNA sequencing in mouse ICH and mRNA sequencing of human ICH from online databases, top five potential signature genes after ICH, Tyrobp, Itgb2, Tlr2, Ptprc and Itgam, were screened. Quantitative PCR results showed higher mRNA expression of Tyrobp, Itgb2, Tlr2, Ptprc, and Itgam in the 1-, 3- and 5-day mouse ICH groups compared to the sham-operated group. Immune infiltration correlation analysis shows that the top-ranked signature gene, Tyrobp, is negatively correlated with M2 macrophages and plasma cells, and Western blot analysis shows higher expression of the Tyrobp protein in the 1-, 3-, and 5-day mouse ICH groups compared to the sham-operated group. Furthermore, immunohistochemistry revealed that TYROBP protein expression was significantly higher in human ICH tissues than in normal brain tissues. Our results suggest that Tyrobp is a signature gene in the acute phase of ICH and may be a potential target for the treatment of the acute phase of ICH.

Abstract Childhood leukemia is a prevalent form of pediatric cancer, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the primary manifestations. Timely treatment has significantly enhanced survival rates for children with acute leukemia. This study aimed to develop an early and comprehensive predictor for hematologic malignancies in children by analyzing nutritional biomarkers, key leukemia indicators, and granulocytes in their blood. Using a machine learning algorithm and ten indices, the blood samples of 826 children with ALL and 255 children with AML were compared to a control group of 200 healthy children. The study revealed notable differences, including higher indicators in boys compared to girls and significant variations in most biochemical indicators between leukemia patients and healthy children. Employing a random forest model resulted in an area under the curve (AUC) of 0.950 for predicting leukemia subtypes and an AUC of 0.909 for forecasting AML. This research introduces an efficient diagnostic tool for early screening of childhood blood cancers and underscores the potential of artificial intelligence in modern healthcare.

Following the coronavirus disease-2019 outbreak caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an ongoing need to seek drugs that target COVID-19. First off, novel drugs have a long development cycle, high investment cost, and are high risk. Second, novel drugs must be evaluated for activity, efficacy, safety, and metabolic performance, contributing to the development cycle, investment cost, and risk. We searched the Cochrane COVID-19 Study Register (including PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and WHO COVID-19 Coronaviral Disease Global Literature to identify completed and ongoing studies as of February 20, 2024. We evaluated the pharmacological effects, in vivo and in vitro data of the 16 candidates in the paper. The difficulty of studying these candidates in clinical trials involving COVID-19 patients, dosage of repurposed drugs, etc. is discussed in detail. Ultimately, Metformin is more suitable for prophylactic administration or mildly ill patients; the combination of Oseltamivir, Tamoxifen, and Dexamethasone is suitable for moderately and severely ill patients; and more clinical trials are needed for Azvudine, Ribavirin, Colchicine, and Cepharanthine to demonstrate efficacy.

Cerebral ischemia-reperfusion injury (CIRI), a prevalent stroke-related complication, can lead to severe brain damage. Inflammation is a crucial factor in CIRI pathogenesis, and the complement component 3a receptor (C3aR) could be a key mediator in the post-CIRI inflammatory cascade. In this study, the role of C3aR in CIRI was investigated utilizing a middle cerebral artery occlusion (MCAO) model in C3aR knockout (KO) mice. Magnetic resonance imaging (MRI) and neurofunctional assessments revealed that C3aR KO mice exhibited significantly diminished cerebral infarction and improved neurological impairments. Consequently, the focus shifted to searching for a small molecule antagonist of C3aR. JR14a, a new potent thiophene antagonist of C3aR, was injected intraperitoneally into mice 1-h post-MCAO model implementation. The mass spectrometry (MS) results indicated the ability of JR14a to penetrate the blood-brain barrier. Subsequent TTC staining and neurofunctional assessments revealed the efficacy of JR14a in reducing cerebral infarct volume and neurological impairment following MCAO. In addition, immunofluorescence (IF) and immunohistochemistry (IHC) demonstrated attenuated microglial activation, neutrophil infiltration, and blood-brain barrier disruption by JR14a in the MCAO model. Furthermore, enzyme-linked immunosorbent assay (ELISA) and Western blotting supported the role of JR14a in downregulating the expression levels of C3aR, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), as well as the phosphorylation of p65. In conclusion, the findings suggested that C3aR could be a potential therapeutic target for CIRI, and JR14a emerged as a promising treatment candidate.

Abstract Accurate identification and localization of multiple abnormalities are crucial steps in the interpretation of chest X-rays (CXRs); however, the lack of a large CXR dataset with bounding boxes severely constrains accurate localization research based on deep learning. We created a large CXR dataset named CXR-AL14, containing 165,988 CXRs and 253,844 bounding boxes. On the basis of this dataset, a deep-learning-based framework was developed to identify and localize 14 common abnormalities and calculate the cardiothoracic ratio (CTR) simultaneously. The mean average precision values obtained by the model for 14 abnormalities reached 0.572-0.631 with an intersection-over-union threshold of 0.5, and the intraclass correlation coefficient of the CTR algorithm exceeded 0.95 on the held-out, multicentre and prospective test datasets. This framework shows an excellent performance, good generalization ability and strong clinical applicability, which is superior to senior radiologists and suitable for routine clinical settings.

Abstract Background The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC. Methods A high throughput liquid chromatography‐tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment‐resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient‐derived organoid (PDO) assays. Results A multiomics profiling of 8536 high‐confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment‐resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5‐lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively. Conclusion Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.

In order to investigate the effects of different drying methods on the properties of porous starch. The present study used four drying methods, namely hot air drying (HD), spray drying (SPD), vacuum freeze drying (FD) and supercritical carbon dioxide drying (SCD) to prepare maize and kudzu porous starch. Findings indicated that the physicochemical properties (e.g., morphology, crystallinity, enthalpy value, porosity, surface area and water absorption capacity as well as dye absorption capacity, particle size) of porous starch were significantly affected by the drying method. Compared with other samples, SCD-treated porous starch exhibited the highest surface areas of the starch (2.943 and 3.139 m2/g corresponding to kudzu and maize, respectively), amylose content (22.02 % and 16.85 % corresponding to kudzu and maize, respectively), MB and NR absorption capacity (90.63 %, 100.26 % and 90.63 %, 100.26 %, corresponding to kudzu ad maize, respectively), and thermal stability, whereas HD-treated porous starch showed the highest water-absorption capacity (123.8 % and 131.31 % corresponding to kudzu and maize, respectively). The dye absorption of the maize and kudzu porous starch was positively correlated with surface area, according to Pearson's correlation analysis. Therefore, in this study, our aim was to explore the effects of different drying methods on the Structure and properties of porous starch, and provide reference for selecting the best drying method for its application in different fields.

The empirical study aimed to explore the relationships among social media exposure, job stress, anxiety, and identity disturbance in a nonclinical setting in the COVID-19 pandemic context. An online questionnaire was administered to 282 participants in the United States of America (USA) during the COVID-19 pandemic. The study utilized a two-step Structural Equation Modeling (SEM) approach consisting of both measurement model and structural model testing. Relationships between the model variables of social media exposure, identity disturbance, anxiety, and job stress were analyzed using standardized beta coefficients, standard errors, t-values, and p-values. The results indicate that both social media exposure and job stress are associated with increased anxiety levels, which, in turn, influence identity disturbance. Moreover, there is a moderating effect of job stress on the relationship between social media exposure and anxiety, as well as the mediating effect of anxiety on the relationship between social media exposure and identity disturbance. The findings are valuable for organizations and can be used to develop programs aimed at mitigating the adverse effects of social media exposure on mental health. Prioritizing employee mental health through awareness and support initiatives is paramount, especially for those facing high stress and extensive social media use.

Innate inflammation is crucial for ischemic stroke development. NLRP6, a nucleotide-binding and oligomerization domain-like receptors (NLRs) family member, regulates innate inflammation. Whether NLRP6 regulates neurological damage and neuroinflammation during ischemic stroke remains unclear. We report that NLRP6 is abundantly expressed in microglia and significantly upregulated in the ischemic brain. The brain injury severity was alleviated in NLRP6-deficient mice after ischemic stroke, as evidenced by reduced cerebral infarct volume, decreased neurological deficit scores, improved histopathological morphological changes, ameliorated neuronal denaturation, and relief of sensorimotor dysfunction. In the co-culture OGD/R model, NLRP6 deficiency prevented neuronal death and attenuated microglial cell injury. NLRP6 deficiency blocked several NLRs inflammasomes' activation and abrogated inflammasome-related cytokine production by decreasing the expression of the common effector pro-caspase-1. NLRP6 deficiency reduced pro-caspase-1's protein level by inducing proteasomal degradation. These findings confirm the neuroprotective role of NLRP6 deficiency in ischemic stroke and its underlying regulation mechanism in neuroinflammation and provide a potential therapeutic target for ischemic stroke.

This research analyzed data from 5106 participants in the National Health and Nutrition Examination Survey 2005–2006 to explore the link between indoor allergen concentrations, serum IgE levels, and allergic diseases. The study found that 14.9% of participants reported having asthma, with significant differences noted in the concentrations of certain indoor allergens, specifically dust dog, mite, and cat allergens, between asthma and non-asthma groups. Furthermore, positivity rates for inhalant allergen-specific IgE and total IgE were higher in the asthma group. However, the correlations between most inhalant allergen IgE, including total IgE, and indoor allergen concentrations were very weak. These findings suggest that the relationship between indoor allergen concentrations and asthma incidence is complex, indicating a potential need for personalized allergen prevention strategies based on disease type and patient sensitization.

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.

Abstract A permanent magnet synchronous machine (PMSM) temperature estimation method fusing the classic lumped‐parameter thermal network (LPTN) and the stator sensor temperature information is investigated. With respect to the industrial servo applications, it is important to monitor the rotor magnet temperature to extend the machine thermal utilisation. A simple LPTN is developed and the quadratic programming is applied to identify the model parameters. The research work shows that the rotor temperature is sensitive to the rotor speed even at low speeds, and this simple estimation network can provide an accurate estimation. The winding sensor information can further improve the performance. A compound mechanism is built, by which the winding temperature estimation error is used as feedback to suppress the model‐based temperature estimation error accumulation. The estimation performance is compared with a regular constant LPTN‐based method. Experimental results based on a PMSM are presented to validate the proposed method.

Background: Body mass index (BMI) is known to affect the outcomes of spirometry indices. However, its association with spirometry indices in COPD and asthma is less studied. We aimed to explore the impact of BMI on these patients.Methods: Patients with COPD or asthma who completed bronchodilator tests (BDTs) between 2017 and 2021 were reviewed. Spirometry indices were compared among patients with COPD or asthma that were subclassified as underweight (BMI< 18.5 kg/m2), normal weight (≥18.5 to < 25), overweight (≥ 25 to < 30), and obesity (≥ 30). Results.Results: Analysis was conducted on 3891 COPD patients (age:66.5 ± 7.8 years) and 1208 asthma patients (age:59.7 ± 7.5 years). COPD patients classified as underweight demonstrated significantly lower values of pre-and post FEV1 (L, %), pre-and post FVC (L, %), and pre- and post-FEV1/FVC (all p < 0.05). In contrast, COPD patients who were overweight or obese exhibited higher values for pre-and post FEV1 (L, %), and pre and post FEV1/FVC (all p < 0.05). Within the cohort of asthma patients, those underweight had lower pre-and post FEV1 (L, %), pre and post FVC (L, %), pre and post FEV1/FVC %. Obese asthma patients displayed higher pre and post FEV1/FVC (all p < 0.05).Conclusion: Significant BMI category differences in spirometry indices can be seen in patients with COPD or asthma. Both underweight and obesity could affect the diagnosis and severity of these diseases. Recognizing these effects is essential to better management and diagnosis of these patients.

Porous starch is a denatured starch product with high porosity, a large specific surface area, and strong adsorption. It is widely used in medicine, food, and chemical industries. Native starch includes types A, B, and C. In this study, the various starch materials, including potato maize, and kudzu starch, were used to prepare different crystal types of porous starch with α-amylase and glucoamylase. The structural and chemical characteristics of the porous starch were measured using Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and differential scanning calorimetry. The results showed that maize , potato and kudzu starches were typically A, B, and C types, respectively. Compared to the native starch, the three types of porous starch treated with α-amylase and Glucoamylase cause varying degrees of destruction of the surface of the starch. Moreover, investigating the reaction factors which are expected to affect the water adsorption capacity were studied systematically, including the mass ratio of α-amylase to glucoamylase (m α-amylase/m glucoamylase), the mass ratio of the total amount of enzymes to starch (m enzyme/m St), enzymatic reaction temperature, and enzymatic reaction time. The results suggested that A-type starch has higher enzymolysis efficiency than other types of starch and can be used to produce ideal cavity and pore-size starch granules with potential applications in many fields.

Abstract Background Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia. Objective This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan‐Kynurenine pathway and the severity of severe pneumonia, as well as N‐3/N‐6 polyunsaturated fatty acids (PUFAs). Methods In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups. Results Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α‐linolenic acid (linolenic acid, α‐LNA), arachidonic acid (ARA), Dihomo‐γ‐linolenic acid (DGLA), and 13(s)‐hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)‐hydroxyeicosatetraenoic acid (HETE), 11(S)‐HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)‐hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α‐LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)‐HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α‐LNA, DHA, and DPA. Conclusion This study revealed that during severe pneumonia, the Tryptophan‐Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan‐Kynurenine pathway was negatively correlated with N‐3/N‐6 PUFAs.

Objectives: Rabies is an acute lethal infectious disease caused by a lyssavirus infection. In 2018, the World Health Organization proposed a global strategic plan to end human rabies deaths by 2030. However, systematic studies on the global rabies disease burden and epidemiological trends are scarce. Methods: We extracted the disease burden and epidemiological data of rabies worldwide in the preceding 30 years from the Global Burden of Disease Study 2019 and performed a comprehensive analysis. Results: In 2019, the incident cases of rabies worldwide were 14,075.51 (95% uncertainty interval: 6124.33-21,618.11), and the number of deaths was 13,743.44 (95% uncertainty interval: 6019.13-17,938.53), both of which were lower than that in 1990. With the improvement of the sociodemographic index, the incident cases, the number of deaths, age-standardized incidence rate, age-standardized incidence death rate, and disability-adjusted life years of rabies all showed downward trends. Adolescents and adults aged

A traumatic hemorrhage is fatal due to the great loss of blood in a short period of time; however, there are a few biomaterials that can stop the bleeding quickly due to the limited water absorption speed. Here, a highly absorbent polymer (HPA), polyacrylate, was prepared as it has the best structure–effectiveness relationship. Within a very short period of time (2 min), HPA continually absorbed water until it swelled up to its 600 times its weight; more importantly, the porous structure comprised the swollen dressing. This instantaneous swelling immediately led to rapid hemostasis in irregular wounds. We optimized the HPA preparation process to obtain a rapidly water-absorbent polymer (i.e., HPA-5). HPA-5 showed favorable adhesion and biocompatibility in vitro. A rat femoral arteriovenous complete shear model and a tail arteriovenous injury model were established. HPA exhibited excellent hemostatic capability with little blood loss and short hemostatic time compared with CeloxTM in both of the models. The hemostatic mechanisms of HPA consist of fast clotting by aggregating blood cells, activating platelets, and accelerating the coagulation pathway via water absorption and electrostatic interaction. HPA is a promising highly water-absorbent hemostatic dressing for rapid and extensive blood clotting after vessel injury.

Transcription factors within microglia contribute to the inflammatory response following intracerebral hemorrhage (ICH). Therefore, we employed bioinformatics screening to identify the potential transcription factor tonicity-responsive enhancer-binding protein (TonEBP) within microglia. Inflammatory stimuli can provoke an elevated expression of TonEBP in microglia. Nevertheless, the expression and function of microglial TonEBP in ICH-induced neuroinflammation remain ambiguous. In our recent research, we discovered that ICH instigated an increased TonEBP in microglia in both human and mouse peri-hematoma brain tissues. Furthermore, our results indicated that TonEBP knockdown mitigates lipopolysaccharide (LPS)-induced inflammation and the activation of NF-κB signaling in microglia. In order to more deeply comprehend the underlying molecular mechanisms of how TonEBP modulates the inflammatory response, we sequenced the transcriptomes of TonEBP-deficient cells and sought potential downstream target genes of TonEBP, such as Pellino-1 (PELI1). PELI has been previously reported to mediate nuclear factor-κB (NF-κB) signaling. Through the utilization of CUT & RUN, a dual-luciferase reporter, and qPCR, we confirmed that TonEBP is the transcription factor of Peli1, binding to the Peli1 promoter. In summary, TonEBP may enhance the LPS-induced inflammation and activation of NF-κB signaling via PELI1.

Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein–protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1β and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.

LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.

The detection of allergen-specific IgE antibodies is an important biomarker for the diagnosis and treatment monitoring of allergic diseases. And the pre-analytical phase is an important part of the overall quality of the laboratory. In this study, 44 patients with allergic diseases (including 23 patients with allergic rhinitis, 12 patients with allergic rhinitis and asthma, and 9 patients with allergic dermatitis) were included in the outpatient center of the Department of Allergy, the First Affiliated Hospital of Guangzhou Medical University. We mixed the serums of the above 44 patients (approximately 0.8 ml of serum volume per patient) into a large volume of serum pool (about 35 ml in total) and divided into 26 parts. And 26 serum samples were stored at 4 different temperatures for 90 days to observe the stability of sIgE antibodies to 16 allergens in serum. The results show that serum sIgE antibody titers in patients with allergic diseases show significant stability during 90 days of storage, even at room temperature. Good stability even after up to 10 freeze-thaw cycles under low temperature storage conditions.

Purpose The relationship between childhood blood eosinophils and subtypes of allergic diseases remains understudied. This study aimed to examine the associations between childhood blood eosinophils and subtypes of asthma, rhinitis and dermatitis, as well as the modifying effect of age.Methods We obtained concurrent blood cell counts and serum Immunoglobulin E (IgE) test results in 5026 children (0–13, years) from First Affiliated Hospital of Guangzhou Medical University from 2014 to 2019. Generalized additive models with multivariable adjustments were utilized to model the exposure-response relationship between eosinophils and allergic symptoms. The robustness of the association was assessed in two age categories (

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp (RGDRGD) 30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus. The active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral effect. However, little is known about the kinetics and degradation products of PEP06 in vitro or in vivo. In this study, we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species; we further identified the degradation characteristics of its cleavage products. PEP06 underwent rapid enzymatic degradation in multiple types of living cells, and the liver, kidney, and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06. We identified metabolites of PEP06 using full-scan mass spectrometry (MS) and tandem MS (MS2), wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide, formed by successive losses of amino acids. The metabolites were C and N terminal truncated products of PEP06. The structures of 11 metabolites (M6, M7, M16, M17, M21, M25, M33, M34, M39, M40, and M42) were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites. We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06, which can support further drug research.

The increasing application of nuclear technology, the high fatality of acute radiation syndrome (ARS) and its complex mechanism make ARS a global difficulty that requires urgent attention. Here we reported that the death receptor 5 (DR5), as well as its ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were both significantly upregulated after irradiation in mice with 6 Gy γ-ray single radiation. And by intravenously administrated with soluble DR5 fusion protein (sDR5-Fc), the competitive antagonist of DR5, the excessive apoptosis in the radiation-sensitive tissues such as spleen and thymus were significantly inhibited and the radiation-induced damage of spleen and thymus were mitigated, while the expression of apoptosis-inhibiting proteins such as Bcl-2 was also significantly upregulated. The biochemical indicators such as serum ALP, AST, ALT, TBIL, K, and Cl levels that affected by radiation, were improved by sDR5-Fc administration. sDR5-Fc can also regulate the number of immune cells and reduce blood cell death. For in vitro studies, it had been found that sDR5-Fc effectively inhibited apoptosis of human small intestinal mucosal epithelial cells and IEC-6 cells using flow cytometry. Finally, survival studies showed that mice administrated with sDR5-Fc after 9 Gy γ-ray single whole body radiation effectively increased the 30-day survival and was in a significant dose-dependent manner. Overall, the findings revealed that DR5/TRAIL-mediated apoptosis pathway had played important roles in the injury of ARS mice, and DR5 probably be a potential target for ARS therapeutics. And the DR5 apoptosis antagonist, sDR5 fusion protein, probably is a promising anti-ARS drug candidate which deserves further investigation.

Radiation-induced skin injury (RISI) is a frequent and severe complication with a complex pathogenesis that often occurs during radiation therapy, nuclear incidents, and nuclear war, for which there is no effective treatment. Hyaluronan (HA) plays an overwhelming role in the skin, and it has been shown that UVB irradiation induces increased HA expression. Nevertheless, to the best of our knowledge, there has been no study regarding the biological correlation between RISI and HA degradation and its underlying mechanisms. Therefore, in our study, we investigated low-molecular-weight HA content using an enzyme-linked immunosorbent assay and changes in the expression of HA-related metabolic enzymes using real-time quantitative polymerase chain reaction and a Western blotting assay. The oxidative stress level of the RISI model was assessed using sodium dismutase, malondialdehyde, and reactive oxygen species assays. We demonstrated that low-molecular-weight HA content was significantly upregulated in skin tissues during the late phase of irradiation exposure in the RISI model and that HA-related metabolic enzymes, oxidative stress levels, the MEK5/ERK5 pathway, and inflammatory factors were consistent with changes in low-molecular-weight HA content. These findings prove that HA degradation is biologically relevant to RISI development and that the HA degradation mechanisms are related to HA-related metabolic enzymes, oxidative stress, and inflammatory factors. The MEK5/ERK5 pathway represents a potential mechanism of HA degradation. In conclusion, we aimed to investigate changes in HA content and preliminarily investigate the HA degradation mechanism in a RISI model under γ-ray irradiation, to consider HA as a new target for RISI and provide ideas for novel drug development.

In recent years, the coagulation properties of inorganic minerals such as kaolin and zeolite have been demonstrated. This study aimed to assess the hemostatic properties of three local clays from China: natural kaolin from Hainan, natural halloysite from Yunnan, and zeolite synthesized by our group. The physical and chemical properties, blood coagulation performance, and cell biocompatibility of the three materials were tested. The studied materials were characterized by using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). All three clays showed different morphologies and particle size, and exhibited negative potentials between pH 6 and 8. The TGA and DSC curves for kaolin and halloysite were highly similar. Kaolin showed the highest water absorption capacity (approximately 93.8% ± 0.8%). All three clays were noncytotoxic toward L929 mouse fibroblasts. Kaolin and halloysite showed blood coagulation effects similar to that exhibited by zeolite, indicating that kaolin and halloysite are promising alternative hemostatic materials.

Abstract Background Smoking is believed as one of the major risk factors resulting in a variety of non-communicable diseases, such as lung cancer and chronic respiratory diseases (CRDs). However, the global burden of CRDs attributed to smoking has not been systematically studied, particularly across different temporal and spatial scales. Methods We conducted a systematic analysis of the Global Burden of CRDs and related risk factors using data from the Global Burden of Disease Study 2019. Incidence, death, risk factors, and other parameters such as estimated annual percentage change have been analyzed. We also compared various risk factors across regions, countries, and genders. Results Globally, the incidence of CRDs and deaths cases have increased in the last 30 years, while the corresponding age-standardized incidence rate (ASIR) and death rate (ASDR) have declined. Smoking was the leading risk factor for the death of CRDs all over the world. However, in low and low-middle Socio-demographic Index (SDI) areas, particulate matter pollution was the main risk factor leading to death from CRDs, while smoking was ranked first among the major risk factors in areas with middle, middle-high, or high SDI. Globally, gender differences in morbidity and mortality from CRDs were observed. Males had slightly more cases and ASIR of chronic respiratory diseases than females over the last 30 years. However, the mortality cases and ASDR in males were significantly higher than that of females. Furthermore, the ASDR of all major risk factors, specially smoking, was higher in men than in women. Conclusions CRDs were still major threats human health. The current study highlights the dominating roles of smoking for death risks resulting from CRDs, followed by PM pollution. Therefore, tobacco control and improving air quality are key to reducing deaths from CRDs.

Background: The prevalence of allergic diseases has increased significantly in China over the last few decades, and there have been very few reports of allergic diseases in certain occupational specialties, with almost no reports among sanitation workers. Objective: Our objective was to investigate the prevalence of allergic diseases and the prevalence of common allergen sensitization in the population engaged in sanitation, and to try to answer the connection between urban garbage waste exposure and the development of allergic diseases. Methods: We conducted a cross-sectional survey of people working in sanitation-related jobs in Liwan District, Guangzhou, China. A total of 893 people completed the questionnaire for this study, and 500 of them were further screened and tested for allergens specific IgE and IgG4. Combining the questionnaire and test results, we investigated the incidence of allergy disorders and patterns of sensitization to allergens in this community, and evaluated the presence of occupational-related risk factors in this particular population. Results: Of the 893 sanitation workers, 166 (18.59%) self-reported allergic diseases, predominantly suffering from allergic rhinitis (AR) (n = 98, 10.97%), followed by drug allergy (n = 31, 3.47%), atopic dermatitis (n = 27, 3.02%), food allergy (n = 21, 2.35%), and asthma (n = 9, 1.00%), in that order. In addition to dust mites (32.20%), which had the highest sensitization rate, the subject population had relatively high sensitization rates to ragweed (7.00%) and moulds mixture (8.20%) when compared with the rates of sensitization to moulds and ragweed in the general population; the top 3 sIgG4 positivity rates were egg (50.00%), milk (10.20%), and soybean (9.40%). The prevalence of self-reported AR was higher in office managers (the control group) than in cleaning staff (the exposed group), but there was no difference in sIgE positivity for serum allergens between the 2 groups. The chance of having AR may increase with management positions (crude OR 2.20, 95% CI 1.38–3.50), P = 0.001). Conclusion: This is the first study to investigate the prevalence of allergy illnesses in the sanitation workforce in mainland China. We identified a community of real sanitation workers with high ragweed and mycobacterial sensitization rates. Urban cleaning may be protective factor against AR at the symptom level, but the serological results did not show this to be the case.

COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer a broad range of applications, including the prevention and treatment of acute infectious diseases. Hundreds of SARS-CoV-2 neutralizing antibody studies are currently underway around the world, with some already in clinical applications. The development of SARS-CoV-2 neutralizing antibody opens up a new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD regions, host cell targets, and cross-neutralizing antibodies), as well as the current scientific evidence for neutralizing-antibody-based treatments based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, and recombinant drugs. The functional evaluation of antibodies (i.e., in vitro or in vivo assays) is also discussed. Finally, some current issues in the field of neutralizing-antibody-based therapies are highlighted.

Abstract The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency (COVID-19) because of its rapid spread and high mortality. Since the virus epidemic, many pathogenic mechanisms have been revealed, and virus-related vaccines have been successfully developed and applied in clinical practice. However, the pandemic is still developing, and new mutations are still emerging. Virus pathogenicity is closely related to the immune status of the host. As innate immunity is the body’s first defense against viruses, understanding the inhibitory effect of SARS-CoV-2 on innate immunity is of great significance for determining the target of antiviral intervention. This review summarizes the molecular mechanism by which SARS-CoV-2 escapes the host immune system, including suppressing innate immune production and blocking adaptive immune priming. Here, on the one hand, we devoted ourselves to summarizing the combined action of innate immune cells, cytokines, and chemokines to fine-tune the outcome of SARS-CoV-2 infection and the related immunopathogenesis. On the other hand, we focused on the effects of the SARS-CoV-2 on innate immunity, including enhancing viral adhesion, increasing the rate of virus invasion, inhibiting the transcription and translation of immune-related mRNA, increasing cellular mRNA degradation, and inhibiting protein transmembrane transport. This review on the underlying mechanism should provide theoretical support for developing future molecular targeted drugs against SARS-CoV-2. Nevertheless, SARS-CoV-2 is a completely new virus, and people’s understanding of it is in the process of rapid growth, and various new studies are also being carried out. Although we strive to make our review as inclusive as possible, there may still be incompleteness.

Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb’s quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS—IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects.

Several studies have shown a link between immunity, inflammatory processes, and epilepsy. Active neuroinflammation and marked immune cell infiltration occur in epilepsy of diverse etiologies. Microglia, as the first line of defense in the central nervous system, are the main effectors of neuroinflammatory processes. Discovery of new biomarkers associated with microglia activation after epileptogenesis indicates that targeting specific molecules may help control seizures. In this research, we used a combination of several bioinformatics approaches, including RNA sequencing, to explore differentially expressed genes (DEGs) in epileptic lesions and control samples, and to construct a protein-protein interaction (PPI) network for DEGs, which was examined utilizing plug-ins in Cytoscape software. Finally, we aimed to identify 10 hub genes in immune and inflammation-related sub-networks, which were subsequently validated in real-time quantitative polymerase chain reaction analysis in a mouse model of kainic acid-induced epilepsy. The expression patterns of nine genes were consistent with sequencing outcomes. Meanwhile, several genes, including CX3CR1, CX3CL1, GPR183, FPR1, P2RY13, P2RY12 and LPAR5, were associated with microglial activation and migration, providing novel candidate targets for immunotherapy in epilepsy and laying the foundation for further research.

Brain hemorrhage: Reducing inflammation and brain damage Treatments that target the proteins responsible for inflammation might reduce brain damage after a hemorrhage. Sudden bleeding into the brain, known as intracerebral hemorrhage (ICH), is associated with strokes and head injuries. Inflammation exacerbates ICH-induced injury after an incident, and is activated by protein complexes called inflammasomes. Jing Zhao and co-workers at Chongqing Medical University in China induced ICH symptoms in rats by extracting arterial blood and injecting it into the basal ganglia of the brain. When they artificially blocked expression of the inflammasome NLRC4, they saw reductions in neuron death, brain edema and damage to the blood-brain barrier. The team also identified a protein critical for activating NLRC4 and another protein that suppresses NLRC4. These findings could aid the development of treatments to block NLRC4 in the days after an ICH.

Unfractionated heparin (UFH) is an anionic glycosaminoglycan that is widely used to prevent blood clotting. However, in certain cases, unwanted side effects can require it to be neutralized. Protamine sulfate (PS), a basic peptide rich in arginine, is the only approved antagonist for UFH neutralization. Many adverse reactions occur with the clinical application of PS, including systemic hypotension, pulmonary hypertension, and anaphylaxis. We previously described R15, a linear peptide composed of 15 arginine molecules, as a potential UFH antagonist. In this study, the in‐depth safety of R15 was explored to reveal its merits and associated risks in comparison with PS. In vitro safety studies investigated the interactions of R15 with erythrocytes, fibrin, complement, and rat plasma. In vivo safety studies explored potential toxicity and immunogenicity of R15 and the UFH–R15 complex. Results showed that both PS and R15 can induce erythrocyte aggregation, thicken fibrin fibers, activate complement, and cause anticoagulation in a concentration‐dependent manner. However, those influences weakened in whole blood or in live animals and were avoided when R15 was in a complex with UFH. We found dramatically enhanced complement activation when there was excess UFH in analyses involving UFH–PS complexes, and a slight increase in those involving UFH–R15 complexes. Within 2 h, R15 was degraded in rat plasma in vitro, whereas PS was not. Enhanced creatinine was found after a single intravenous injection of PS or R15 (900 U·kg−1, body weight), suggesting possible abnormal renal function. The UFH–PS complex, but not the UFH–R15 complex, exhibited obvious immunogenicity. In conclusion, R15 is nonimmunogenic and potentially safe at a therapeutic dose to reverse the effects of UFH.

Duplilumab is approved to treat mild to moderate atopic dermatitis. It is unclear, however, whether Dupilumab is effective for occupational hand eczema. In this article, we describe a 29-year-old nurse who developed severe hand eczema after working in a hospital for 6 years and received inadequate relief from routine treatment. Duplilumab was administered to the patient with great results.

Background: The impact of deaths and disability-adjusted life years (DALYs) caused by air pollution in China has not been well elucidated. We aimed to analyze the association of air pollution with deaths and DALYs in the Chinese population.Methods: We extracted data on burden due to deaths and disability-adjusted life years attributed to air pollution in the previous 30 years in China from the Global Burden of Disease (GBD) study 2019 and performed a comprehensive analysis and summary.Results: 1.85 (95% UI: 1.57–2.17) million Chinese people lost their lives as a result of air pollution in 2019, a slight decrease from 1990. In 2019, the disability-adjusted life years (DALYs) caused by air pollution in China was 42.51 (95% UI: 36.34–49.48) million, a 30.2% decrease from 1990. From 1990 to 2019, both age-standardized death rate (ASDR) and age-standardized DALYs due to air pollution in China showed a significant year-on-year downward trend. Air pollution–related deaths and DALYs occurred mostly in people over the age of 50 years. Stroke, ischemic heart disease, and chronic obstructive pulmonary disease were attributed the maximum death burden due to air pollution in China in 2019.Conclusion: Over the past 30 years, air pollution has brought a heavy disease burden to China, and in the future, joint efforts are required to improve the air quality.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 μm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model’s establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.

Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high disability rate and high mortality, and pyroptosis is a type of programmed cell death in the acute phase of ICH. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is a specific transcription factor highly expressed in the nervous system, yet the role of NPAS4 in ICH-induced pyroptosis is not fully understood. NLR family Pyrin-domain-containing 6 (NLRP6), a new member of the Nod-like receptor family, aggravates pyroptosis via activating cysteine protease-1 (Caspase-1) and Caspase-11. In this study, we found that NPAS4 was upregulated in human and mouse peri-hematoma brain tissues and peaked at approximately 24 h after ICH modeling. Additionally, NPAS4 knockdown improved neurologic dysfunction and brain damage induced by ICH in mice after 24 h. Meanwhile, inhibiting NPAS4 expression reduced the levels of myeloperoxidase (MPO)-positive cells and Caspase-1/TUNEL-double-positive cells and decreased cleaved Caspase-1, cleaved Caspase-11, and N-terminal GSDMD levels. Consistently, NPAS4 overexpression reversed the above alternations after ICH in the mice. Moreover, NPAS4 could interact with the Nlrp6 promoter region (−400–−391 bp and −33–−24 bp) and activate the transcription of Nlrp6. Altogether, our study demonstrated that NPAS4, as a transcription factor, can exacerbate pyroptosis and transcriptionally activate NLRP6 in the acute phase of intracerebral hemorrhage in mice.

Objective: To develop an UPLC-MS/MS method for the accurate quantification of Estriol (E3), a new radioprotective agent, and observe the variation in pharmacokinetic characteristics of E3 after irradiation. As a hormone drug, the gender differences of E3 metabolism were also concerned here. Methods: Various chromatographic and mass spectrometric conditions of E3 were optimized. The specificity, linearity, precision and accuracy of UPLC-MS/MS method were validated. Twenty SD rats, half male and half female, were administered with intramuscular (im) injection of 2.7 ​mg/kg E3, and then divided randomly into two groups, sham-irradiated group (Con) and irradiated group (IR). IR group was irradiated to 7 ​Gy of γ-rays. Blood samples were collected at different times post-irradiation and E3 concentrations were detected. The changes of concentration-time variation and pharmacokinetic parameters for E3 after irradiation were investigated, together with metabolic differences between male and female rats. Results: The range of the calibration curve of UPLC-MS/MS for E3 was 1.00–200.0 ​ng/mL. Con group reached maximum concentration (Cmax) (77.57 ​± ​18.71) ng/mL at (0.68 ​± ​0.29) h (Tmax) after im injection. The drug concentration-time profiles and pharmacokinetic parameters of E3 were consistent before and after irradiation. The areas under time curve (AUC0-t) of E3 were (353 ​± ​74) h·ng/mL for Con group, and (299 ​± ​74) h·ng/mL for IR group (P ​> ​0.05). There were also no statistical differences in pharmacokinetic parameters between female and male rats. The elimination half-lifes (T1/2) of males and females were (3.02 ​± ​0.68) h and (3.01 ​± ​0.42) h in Con group, and (3.64 ​± ​0.51) h and (3.38 ​± ​0.60) h in IR group, respectively (P ​> ​0.05). Conclusion: A rapid and sensitive UPLC-MS/MS method for determination of E3 was established. The pharmacokinetic characteristics of E3 in rat were not affected by 7 ​Gy irradiation and gender differences. This study provided a theoretical basis for the development and application of new radiation injury treatment drug.

Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future.

Introduction: To identify organs to which dose limitation using intensity modulated radiotherapy (IMRT) can potentially modify the incidence and duration of feeding tube use, during and immediately following therapy for head and neck cancer. Materials and methods: One hundred and fourteen patients treated with definitive IMRT (± concurrent chemotherapy) head and neck mucosal cancers were included. Patients received a prophylactic feeding tube and followed up by a dietician for at least eight weeks post-radiotherapy. Salivary and swallowing organs were delineated for each patient. Tumour and dosimetric variables were recorded for all patients and analysed for incidence and duration of feeding tube use for at least 25% of dietary requirements. Results: Multivariate analysis showed T-classification ≥3 and level II lymphadenopathy as independent significant predictors of incidence and duration of feeding tube use in oral cavity, pharyngeal and supraglottic primaries. Mean dose deposited in the cervical oesophagus over 36Gy further increased the incidence and duration of feeding tube use. Mean dose deposited in the base of tongue and superior pharyngeal constrictor muscles affected incidence and duration of feeding tube use, respectively. Discussion: In patients treated with definitive IMRT, T-classification and Level II lymphadenopathy, combined with a mean cervical oesophagus dose over 36Gy can a stratify patients into eight distinct risk groups for using feeding tubes for at least 25% of their dietary requirements.

Abstract Introduction Precision radiotherapy relies heavily on optimal weight management. Our group previously developed a risk stratification model for patients at risk of prolonged feeding tube (FT) intervention. The study objective was to assess on‐treatment weight loss according to stratified risk of prolonged FT use. Methods One hundred and one (n = 101) definitive head and neck radiotherapy patients were included in this study. Patients were stratified into high risk (HRi: T‐classification ≥ 3 with level 2 Nodal disease), high‐intermediate risk (HIRi: T‐classification ≥ 3 without level 2 Nodes) and low‐intermediate risk (LIRi: T‐classification

The mole fraction of deacetylated monomeric units in chitosan (CS) molecules is referred to as CS’s degree of deacetylation (DD). In this study, 35 characteristic ions of CS were detected using liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS/MS). The relative response intensity of 35 characteristic ion pairs using a single charge in nine CS samples with varying DDs was analyzed using 30 analytical methods. There was a good linear relationship between the relative response intensity of the characteristic ion pairs determined using ultrahigh performance (UP) LC–MS/MS and the DD of CS. The UPLC–MS/MS method for determining the DD of CS was unaffected by the sample concentration. The detection instrument has a wide range of application parameters with different voltages, high temperatures, and gas flow conditions. This study established a detection method for the DD of CS with high sensitivity, fast analysis, accuracy, stability, and durability.

Uncontrolled hemorrhage from trauma or surgery can lead to death. In this study, chitosan/kaolin (CSK) and chitosan/montmorillonite (CSMMT) composites were prepared from chitosan (CS), kaolin (K), and montmorillonite (MMT) as raw materials to control bleeding. The physiochemical properties and surface morphology of CSK and CSMMT composites were analyzed by Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), zeta potentials, and X-ray fluorescence (XRF). The hemostatic mechanism was measured in vitro by activated partial thromboplastin time (APTT), prothrombin time (PT), in vitro clotting time, erythrocyte aggregation, and thromboelastogram (TEG). The hemostasis ability was further verified by using tail amputation and arteriovenous injury models in rats. The biocompatibility of CSK and CSMMT was evaluated by in vitro hemolysis, cytotoxicity assays, as well as acute toxicity test and skin irritation tests. The results show that CSK and CSMMT are promising composite materials with excellent biocompatibility and hemostatic properties that can effectively control bleeding.

Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-β1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.

Background Glioblastoma relapse is associated with activation of phosphatidylinositol 3-kinase (PI3K) signalling pathway. In preclinical studies, the pan-PI3K inhibitor buparlisib showed antitumour activity in glioma models.Methods This was a two-part, multicentre, phase Ib/II study in patients with recurrent glioblastoma pretreated with radiotherapy and temozolomide standard of care. Patients received buparlisib (80 mg or 100 mg once daily) plus carboplatin (area under the curve (AUC)=5 every 3 weeks), or buparlisib (60 mg once daily) plus lomustine (100 mg/m2 every 6 weeks). The primary endpoint was to determine the maximum tolerable dose (MTD) and/or recommended phase II dose of buparlisib plus carboplatin or lomustine.Results Between 28 February 2014 and 7 July 2016, 35 patients were enrolled and treated with buparlisib plus carboplatin (n=17; buparlisib (80 mg) plus carboplatin, n=3; and buparlisib (100 mg) plus carboplatin, n=14), or buparlisib (60 mg) plus lomustine (n=18). The MTD of buparlisib was determined to be 100 mg per day in combination with carboplatin at an AUC of 5 every 3 weeks. The MTD of buparlisib in combination with lomustine could not be determined as it did not satisfy the MTD criteria per the Bayesian logistic regression model.Conclusion The overall safety profile of buparlisib remained unchanged, and no new or unexpected safety findings were reported in this study. Preliminary assessment for both combinations did not demonstrate sufficient antitumour activity compared with historical data on single-agent carboplatin or lomustine.Trial registration number NCT01934361.

Radiotherapy plays an important role of managing head and neck squamous cell carcinoma (HNSCC). Concurrent radiotherapy with radiosensitizing cisplastin chemotherapy is the standard of care (SOC) for non-operable locally advanced HNSCC. Cetuximab, a monoclonal antibody of epidermal growth factor receptor, was the most extensively studied targeted therapy as a chemo-sparing agent that was used concurrently with radiotherapy. Immunotherapy is used in the treatment of metastatic HNSCC. There is evidence to support the synergistic effect when combining radiotherapy with immunotherapy to potentiate anti-tumor immune response. There has been increasing interest to incorporate immune checkpoint inhibitor (ICI) with radiotherapy in the curative setting for HNSCC. In this review, we discuss the latest evidence that supports concurrent radiotherapy with cisplatin which remains the SOC for locally advanced HNSCC (LA-HNSCC). Cetuximab is suitable for patients who are not fit for cisplatin. We then summarize the clinical trials that incorporate ICI with radiotherapy for LA-HNSCC in concurrent, neoadjuvant, and adjuvant settings. We also discuss the potential of combining immunotherapy with radiotherapy as a treatment de-escalating strategy in HPV-associated oropharyngeal carcinoma. Finally, the pre-clinical and clinical evidence of the abscopal effect when combining stereotactic body radiotherapy with ICIs is presented.