Parameter identification of Johnson-Cook constitutive model based on genetic algorithm and simulation analysis for 304 stainless steel.

Addressing the significant discrepancy between actual experimental cutting force and its predicted values derived from traditional constitutive model parameter identification methods, a reverse identification research of the Johnson-Cook (J-C) constitutive model for 304 stainless steel was conducted via genetic algorithm. Considering actual cutting zone and the influence of feed motion on the rake (flank) angle, an unequal division shear zone model was established to implement the theoretical calculation for shear zone stress. Through cutting experiments, the spindle speed was negatively correlated with the cutting force at first, and then became positively correlated; The empirical formula (EXP model) for turning force was corrected, revealing that the EXP model was unable to provide optimal predicted values for cutting force. The influence of the J-C constitutive parameter C on the cutting morphology was firstly investigated through simulation analysis, and determined an appropriate value for C, then obtained the precise values for the other four constitutive parameters by genetic algorithm. Moreover, the simulated values of cutting force in JC1 model (obtained from the Split Hopkinson Pressure Bar test) and JCM model (the improved model using genetic algorithm) were obtained by three-dimensional (3-D) simulation via FEM software. The results indicated that, the maximum error between actual experimental cutting force and its simulated values (by JCM model) was 14.8%, with an average error of 6.38%. These results outperformed the JC1 and EXP models, suggesting that the JCM model identified via genetic algorithm was more reliable.

[Clinical application of retroauricular hairline approach in submandibular gland resection assisted by endoscope].

Objective:To investigate the clinical effect of retroauricular hairline approach in submandibular gland resection assisted by endoscope. Methods:A total of 18 patients with submandibular gland benign tumors treated in our hospital from September 2022 to September 2023 were selected. A 5 cm incision was designed in the retroauricular hairline, and the flap was turned over directly to the anterior edge of sternocleidomastoid muscle, then the flap was turned over to build the cavity through endoscopic surgery, and submandibular gland resection was completed with the assistance of endoscope. After operation, a negative pressure drainage was placed into the hairline, and the wound was closed by continuous intracutaneous suture. The clinical effect was evaluated after 3-6 months follow-up. Results:All patients underwent submandibular gland resection with endoscopic assistance as planned, and none of them converted to submaxillary incision during operation. The operation time was 65-97 min, with an average of 75 min. Intraoperative bleeding was 10-20 mL, with an average of 14 mL.No tongue numbness, wound infection, or tumor recurrence occurred after operation. However, there were 10 patients with ear numbness and discomfort of auricle after surgery, which gradually recovered after 6-9 months of follow-up. Two patients had crooked mouth after surgery, and the symptoms were gradually relieved after follow-up. All incisions healed in stage I and were concealed. Conclusion:Endoscopic retroauricular hairline approach is a choice for submandibular gland resection with good cosmetic effect, less trauma and fewer complications.

Perovskite Probe-Based Machine Learning Imaging Model for Rapid Pathologic Diagnosis of Cancers.

Accurately distinguishing tumor cells from normal cells is a key issue in tumor diagnosis, evaluation, and treatment. Fluorescence-based immunohistochemistry as the standard method faces the inherent challenges of the heterogeneity of tumor cells and the lack of big data analysis of probing images. Here, we have demonstrated a machine learning-driven imaging method for rapid pathological diagnosis of five types of cancers (breast, colon, liver, lung, and stomach) using a perovskite nanocrystal probe. After conducting the bioanalysis of survivin expression in five different cancers, high-efficiency perovskite nanocrystal probes modified with the survivin antibody can recognize the cancer tissue section at the single cell level. The tumor to normal (T/N) ratio is 10.3-fold higher than that of a conventional fluorescent probe, which can successfully differentiate between tumors and adjacent normal tissues within 10 min. The features of the fluorescence intensity and pathological texture morphology have been extracted and analyzed from 1000 fluorescence images by machine learning. The final integrated decision model makes the area under the receiver operating characteristic curve (area under the curve) value of machine learning classification of breast, colon, liver, lung, and stomach above 90% while predicting the tumor organ of 92% of positive patients. This method demonstrates a high T/N ratio probe in the precise diagnosis of multiple cancers, which will be good for improving the accuracy of surgical resection and reducing cancer mortality.

The reduced cortical bone density in vertebral bodies: risk for osteoporotic fractures? Insights from CT analysis.

BACKGROUND: There is a corresponding increase in the prevalence of osteoporosis and related fractures with the aging population on the rise. Furthermore, osteoporotic vertebral compression fractures (OVCF) may contribute to higher patient mortality rates. It is essential to conduct research on risk factors for OVCF and provide a theoretical basis for preventing such fractures. METHODS: We retrospectively recruited patients who had spine CT for OVCF or back pain. Demographic and CT data were collected. Quantitative computed tomography (QCT) software analyzed the CT data, using subcutaneous fat and paraspinal muscles as reference standards for BMD processing. BMD of cortical and cancellous bones in each patient's vertebral body was determined. RESULTS: In this study, 144 patients were divided into non-OVCF (96) and OVCF (48) groups. Non-OVCF patients had higher cortical BMD of 382.5 ± 52.4 to 444.6 ± 70.1 mg/cm3, with T12 having the lowest BMD (p < 0.001, T12 vs. L2). Cancellous BMD ranged from 128.5 ± 58.4 to 140.9 ± 58.9 mg/cm3, with L3 having the lowest BMD. OVCF patients had lower cortical BMD of 365.0 ± 78.9 to 429.3 ± 156.7 mg/cm3, with a further decrease in T12 BMD. Cancellous BMD ranged from 71.68 ± 52.07 to 123.9 ± 126.2 mg/cm3, with L3 still having the lowest BMD. Fractured vertebrae in OVCF patients (T12, L1, and L2) had lower cortical bone density compared to their corresponding vertebrae without fractures (p < 0.05). CONCLUSIONS: T12 had the lowest cortical BMD and L3 had the lowest cancellous BMD in OVCF patients, with T12 also having the highest incidence of osteoporotic fractures. These findings suggest that reduction in cortical BMD has a greater impact on OVCF than reduction in cancellous BMD, along with biomechanical factors.

Developing and Validating a Nomogram for Non-Adherence to Inhaler Therapy Among Elderly Chronic Obstructive Pulmonary Disease Patients Based on the Social Ecological Model.

Purpose: This study aimed to identify the risk predictors of non-adherence to inhaler therapy and construct a nomogram prediction model for use in Chinese elderly patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: A cross-sectional study was conducted with 305 participants recruited from a tertiary care hospital in Anhui, China. Adherence was analyzed using the Test of Adherence to Inhalers. Potential predictive factors were incorporated based on the social ecological model, and data were collected through a questionnaire method. R version 4.3.3 was utilized to perform the least absolute shrinkage and selection operator regression model and multivariable logistic regression analysis to identify risk factors and establish a nomogram prediction model. Results: The results of the multivariable analysis revealed that medication beliefs, illness perception, the COPD Assessment Test score, smoking status, and education level were significant risk factors for non-adherence to inhaler therapy in elderly COPD patients (all P < 0.05). The nomogram prediction model for non-adherence to inhaler therapy in elderly COPD patients demonstrated a good discriminative ability, with an area under the receiver operating characteristic curve of 0.912. The C-index was 0.922 (95% CI: 0.879 to 0.965), and the Brier value was 0.070, indicating good consistency and calibration. Decision curve analysis indicated that the use of the nomogram would be more beneficial in clinical practice when the threshold probability of non-adherence exceeds 17%. Conclusion: This study identified predictive factors regarding non-adherence among elderly patients with COPD and constructed a predictive nomogram. By utilizing the nomogram model healthcare professionals could swiftly calculate and comprehend the non-compliance level of COPD patients, thus guiding the development of personalized interventions in clinical practice.

Application of Multi-Rod Constructs for the Revision of Thoracolumbar Fractures.

OBJECTIVE: The revision procedure for failure of internal fixation after thoracolumbar fracture is controversial. Combined anterior and posterior surgery is associated with higher risk more intraoperative bleeding and tissue damage. The success rate of simple anterior surgery needs further confirmation, and posterior surgery lacks stability of internal fixation. This study evaluates the feasibility and surgical effect of multi-rod constructs in the revision of thoracolumbar fractures. METHODS: Eleven patients with thoracolumbar fractures who underwent previous construct failure and were treated with revision and internal fixation with the multi-rod technique from March 2017 to September 2018 were analyzed. The original internal fixation was removed and replaced in the medial insertion of satellite rods and bone graft. The average follow-up time was 15.97 months. The intraoperation blood loss, the time of the operation, activation and discharge and the rate of rod fracture were calculated. The sagittal Cobb angle before revision, after revision and at the last follow-up were compared. The clinical effect was evaluated by visual analogue scale (VAS) and Oswestry Disability Index questionnaire (ODI). RESULTS: The average operation time was 107 min, the intraoperative blood loss was 131.81 mL, the active time was 1.59 days, and the discharge time was 10.89 days. No rod fractured again during the follow-up period. The paired t-test was used to compare the Cobb angle, VAS score, and ODI before and after surgery. There was significant difference in the sagittal Cobb angle between the pre-revision and the posterior sagittal position (p = 0.000), and no significant difference was found between post-revision and last follow-up (p = 0.551). VAS and ODI were greatly improved at the last follow-up. CONCLUSION: The literature on revision of thoracolumbar fractures is insufficient and comprises varying opinions. This paper proposes a new treatment option. The application of the multi-rod constructs in the revision of thoracolumbar fractures is safe, simple, and effective and might provide guidance for future clinical work.

Machine Learning-Assisted High-Throughput Identification and Quantification of Protein Biomarkers with Printed Heterochains.

Advanced in vitro diagnosis technologies are highly desirable in early detection, prognosis, and progression monitoring of diseases. Here, we engineer a multiplex protein biosensing strategy based on the tunable liquid confinement self-assembly of multi-material heterochains, which show improved sensitivity, throughput, and accuracy compared to standard ELISA kits. By controlling the material combination and the number of ligand nanoparticles (NPs), we observe robust near-field enhancement as well as both strong electromagnetic resonance in polymer-semiconductor heterochains. In particular, their optical signals show a linear response to the coordination number of the semiconductor NPs in a wide range. Accordingly, a visible nanophotonic biosensor is developed by functionalizing antibodies on central polymer chains that can identify target proteins attached to semiconductor NPs. This allows for the specific detection of multiple protein biomarkers from healthy people and pancreatic cancer patients in one step with an ultralow detection limit (1 pg/mL). Furthermore, rapid and high-throughput quantification of protein expression levels in diverse clinical samples such as buffer, urine, and serum is achieved by combining a neural network algorithm, with an average accuracy of 97.3%. This work demonstrates that the heterochain-based biosensor is an exemplary candidate for constructing next-generation diagnostic tools and suitable for many clinical settings.

ENDOGENOUS ß 3 -ADRENERGIC RECEPTOR ACTIVATION ALLEVIATES SEPSIS-INDUCED CARDIOMYOCYTE APOPTOSIS VIA PI3K/AKT SIGNALING PATHWAY.

ABSTRACT: ß 3 -adrenergic receptor (ß 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of ß 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of ß 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that ß 3 -AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of ß 3 -AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with ß 3 -AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8, and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-Akt Ser473 and p-eNOS Ser1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of ß 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous ß 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression 1-6 . Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic 7-9 . The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach 10-12 to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.

Quantitative analysis of the impact of respiratory state on the heartbeat-induced movements of the heart and its substructures.

PURPOSE: This study seeks to examine the influence of the heartbeat on the position, volume, and shape of the heart and its substructures during various breathing states. The findings of this study will serve as a valuable reference for dose-volume evaluation of the heart and its substructures in radiotherapy for treating thoracic tumors. METHODS: Twenty-three healthy volunteers were enrolled in this study, and cine four-dimensional magnetic resonance images were acquired during periods of end-inspiration breath holding (EIBH), end-expiration breath holding (EEBH), and deep end-inspiration breath holding (DIBH). The MR images were used to delineate the heart and its substructures, including the heart, pericardium, left ventricle (LV), left ventricular myocardium, right ventricle (RV), right ventricular myocardium (RVM), ventricular septum (VS), atrial septum (AS), proximal and middle portions of the left anterior descending branch (pmLAD), and proximal portion of the left circumflex coronary branch (pLCX). The changes in each structure with heartbeat were compared among different respiratory states. RESULTS: Compared with EIBH, EEBH increased the volume of the heart and its substructures by 0.25-3.66%, while the average Dice similarity coefficient (DSC) increased by - 0.25 to 8.7%; however, the differences were not statistically significant. Conversely, the VS decreased by 0.89 mm in the left-right (LR) direction, and the displacement of the RV in the anterior-posterior (AP) direction significantly decreased by 0.76 mm (p < 0.05). Compared with EIBH and EEBH, the average volume of the heart and its substructures decreased by 3.08-17.57% and 4.09-20.43%, respectively, during DIBH. Accordingly, statistically significant differences (p < 0.05) were observed in the volume of the heart, pericardium, LV, RV, RVM, and AS. The average DSC increased by 0-37.04% and - 2.6 to 32.14%, respectively, with statistically significant differences (p < 0.05) found in the right ventricular myocardium and interatrial septum. Furthermore, the displacements under DIBH decreased in the three directions (i.e.,- 1.73 to 3.47 mm and - 0.36 to 2.51 mm). In this regard, the AP displacement of the heart, LV, RV, RVM, LR direction, LV, RV, and AS showed statistically significant differences (p < 0.05). The Hausdorff distance (HD) of the heart and its substructures under the three breathing states are all greater than 11 mm. CONCLUSION: The variations in the displacement and shape alterations of the heart and its substructures during cardiac motion under various respiratory states are significant. When assessing the dose-volume index of the heart and its substructures during radiotherapy for thoracic tumors, it is essential to account for the combined impacts of cardiac motion and respiration.

UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors.

The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

What happens to the osteoporotic bone mesenchymal stem cells? Evidence from RNA sequencing.

Evidence presented that osteoporosis is closely related to the dysfunction of bone mesenchymal stem cells (BMSCs). But most studies are insufficient to reveal what actually happens to the osteoporotic BMSCs. In this study, BMSCs were harvested from ovariectomized and sham-operated rats. After checking the characteristics of rat models and stem cells, the BMSCs were carried out for RNA sequencing. Part of the findings were verified that seven mRNAs (Abi3bp, Aifm3, Ccl11, Cdkn1c, Chst10, Id2, Vcam1) were significantly up-regulated in osteoporotic BMSCs while seven mRNAs (Cep63, Fgfr3, Myc, Omd, Pou2f1, Smarcal1, Timm10b) were down-regulated. In addition, potential miRNA-mRNA and lncRNA-mRNA regulatory networks were illustrated. The changes in osteoporotic BMSCs covered a large set of biological processes, including cell viability, differentiation, immunoreaction, bone repairment and estrogen defect. This study enriched the pathophysiological mechanisms of BMSCs and osteporosis, as well as provided dozens of attractive RNA targets for further treatment.

Printed Divisional Optical Biochip for Multiplex Visualizable Exosome Analysis at Point-of-Care.

Rapid detection of various exosomes is of great significance in early diagnosis and postoperative monitoring of cancers. Here, a divisional optical biochip is reported for multiplex exosome analysis via combining the self-assembly of nanochains and precise surface patterning. Arising from resonance-induced near-field enhancement, the nanochains show distinct color changes after capturing target exosomes for direct visual detection. Then, a series of divisional nanochain-based biochips conjugated with several specific antibodies are fabricated through designed hydrophilic and hydrophobic patterns. Because of the significant wettability difference, one sample droplet is precisely self-splitting into several microdroplets enabling simultaneous identification of multiple target exosomes in 30 min with a sensitivity of 6 × 107 particles mL-1 , which is about two orders lower than enzyme-linked immunosorbent assay. Apart from the trace amount detection, excellent semiquantitative capability is demonstrated to distinguish clinical exosomes from glioblastoma patients and healthy people. This method is simple, versatile, and highly efficient that can be extended as a diagnostic tool for many diseases, promoting the development of liquid biopsy.

Natural bioactive lysosomes extracted from multiple cells for tumor therapy.

Nanoparticles of biological origin exhibit many unique properties in biological applications due to their exquisite structure, specific composition, and natural biological functionality. In this study, we obtained lysosomes from three distinct cell types (one normal cell and two activated immune cells) and demonstrated their potential as natural therapeutic nanoparticles for tumor therapy. In vitro experiments revealed that these lysosomes maintained their structural integrity, were well-distributed, and exhibited significant biological activity, which effectively induced cancer cell death by generating ROS and disrupting biological substrates. Additionally, in vivo investigations showed that these lysosomes could accumulate in tumor tissues after intravenous administration and exhibited exceptional therapeutic effects through the destruction of tumor blood vessels and the degradation of immunosuppressive proteins, with complete tumor disappearance in a single treatment. This research on the utilization of bioactive lysosomes for tumor treatment provides valuable insights into drug development and tumor treatment, particularly when conventional approaches have proven ineffective.

α 2 -ADRENORECEPTOR ANTAGONIST AMELIORATES SEPSIS-ASSOCIATED PULMONARY FIBROSIS BY SUPPRESSING NOREPINEPHRINE-MEDIATED FIBROBLAST DIFFERENTIATION VIA INHIBITING PKC ACTIVATION.

ABSTRACT: Pulmonary fibrosis is an important factor affecting the prognosis of severe septic patients with acute lung injury. The objective of this study was to explore the effect of norepinephrine (NE) and α 2 -adrenoreceptor (AR) on sepsis-associated pulmonary fibrosis and the mechanism underlying these effects. We found pulmonary fibrotic changes, and increased NE production and α 2A -AR expression in the pulmonary tissue of mice subjected to cecal ligation and puncture surgery. Reserpine and yohimbine alleviated pulmonary fibrosis in mice with sepsis by exhausting NE derived from the lung's adrenergic nerve and blocking α 2 -AR, respectively. There was no significant difference in the expression of the three α 1 -AR subtypes. The effect of NE on promoting pulmonary fibroblast differentiation in vitro was suppressed by yohimbine. Both the protein and mRNA expression levels of α 2A -AR were increased in pulmonary fibroblasts treated with LPS. Clonidine, a selective α 2 -AR agonist, enhanced LPS-induced differentiation in pulmonary fibroblasts, as indicated by the increase in α-smooth muscle actin and collagen I/III, which was mitigated by inhibiting PKC and p38. Further in vivo results indicated that yohimbine alleviated pulmonary fibrosis and inhibited the phosphorylation of PKC, p38, and Smad2/3 in lung tissue of mice exposed to LPS for 4 weeks. Clonidine showed the opposite effect to yohimbine, which aggravated LPS-induced pulmonary fibrosis. These findings demonstrated that the sepsis-induced increase in NE promoted fibroblast differentiation via activating α 2 -AR. Blockage of α 2 -AR effectively ameliorated sepsis-associated pulmonary fibrosis by abolishing NE-induced lung fibroblast differentiation and inhibiting the PKC-p38-Smad2/3 pathway.

Using RegGAN to generate synthetic CT images from CBCT images acquired with different linear accelerators.

BACKGROUND: The goal was to investigate the feasibility of the registration generative adversarial network (RegGAN) model in image conversion for performing adaptive radiation therapy on the head and neck and its stability under different cone beam computed tomography (CBCT) models. METHODS: A total of 100 CBCT and CT images of patients diagnosed with head and neck tumors were utilized for the training phase, whereas the testing phase involved 40 distinct patients obtained from four different linear accelerators. The RegGAN model was trained and tested to evaluate its performance. The generated synthetic CT (sCT) image quality was compared to that of planning CT (pCT) images by employing metrics such as the mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). Moreover, the radiation therapy plan was uniformly applied to both the sCT and pCT images to analyze the planning target volume (PTV) dose statistics and calculate the dose difference rate, reinforcing the model's accuracy. RESULTS: The generated sCT images had good image quality, and no significant differences were observed among the different CBCT modes. The conversion effect achieved for Synergy was the best, and the MAE decreased from 231.3 ± 55.48 to 45.63 ± 10.78; the PSNR increased from 19.40 ± 1.46 to 26.75 ± 1.32; the SSIM increased from 0.82 ± 0.02 to 0.85 ± 0.04. The quality improvement effect achieved for sCT image synthesis based on RegGAN was obvious, and no significant sCT synthesis differences were observed among different accelerators. CONCLUSION: The sCT images generated by the RegGAN model had high image quality, and the RegGAN model exhibited a strong generalization ability across different accelerators, enabling its outputs to be used as reference images for performing adaptive radiation therapy on the head and neck.

Case Report: MR-LINAC-guided adaptive radiotherapy for gastric cancer.

Background: The stomach is one of the most deformable organs. Its shape can be easily affected by breathing movements, and daily diet, and it also varies when the body position is different. The susceptibility of stomach has made it challenging to treat gastric cancer using the conventional image-guided radiotherapy, i.e., the techniques based on kilovoltage X-ray imaging. The magnetic resonance imaging guided radiotherapy (MRgRT) is usually implemented using a hybrid system MR-LINAC. It is feasible to implement adaptive radiotherapy using MR-LINAC for deformable organs such as stomach. In this case report, we present our clinical experience to treat a gastric cancer patient using MR-LINAC. Case description: The patient is a 58-year-old male who started having black stools with no apparent cause a year ago. Gastroscopy result showed pancreatic cancer, pathology: adenocarcinoma on gastric cancer biopsy, adenocarcinoma on gastric body minor curvature biopsy. The patient was diagnosed with gastric cancer (adenocarcinoma, cTxN+M1, stage IV, HER-2 positive). The patient was treated in 25 fractions with radiotherapy using MR-LINAC with online adaptive treatment plans daily. The target area in daily MR images varied considerably when compared with the target area on the CT simulation images. During the course of treatment, there have even been instances where the planned target area where the patient received radiotherapy did not cover the lesion of the day. Conclusion: Online adaptive MRgRT can be a meaningful innovation for treating malignancies in the upper abdomen. The results in the current study are promising and are indicative for further optimizing online adaptive MRgRT in patients with inoperable tumors of the upper abdomen.

The Increasing Burden of Cancer Among Women and in Rural Areas: A Retrospective Population-Based Study.

The retrospective study aimed to describe the epidemiological characteristics and trends of cancer in Anhui Province, China between 2010 and 2018. Cancer registry data were analyzed using the Joinpoint regression model to calculate trends in cancer incidence and mortality. Age-standardized incidence rate, calculated based on the world Segi's population (ASIRW) was higher in males (239.34 per 100 000) than in females (157.13 per 100 000), and higher in rural areas (203.98 per 100 000) compared to urban areas (189.93 per 100 000). The ASIRW for males decreased with an AAPC of -3.0%, while that of females showed an upward trend with an AAPC of 2.1%. At the same time, the ASIRW in urban areas decreased with an AAPC of -2.4%, whereas it remained relatively stable in rural areas. Among males, lung cancer was the most prevalent type of cancer, while breast cancer was the most frequent cancer among women. The age-standardized mortality rate according to the world Segi's population (ASMRW) was 115.32 per 100 000. The ASMRW was higher in males (156.70 per 100 000) than in females (75.51 per 100 000), and higher in rural areas (122.18 per 100 000) than urban areas (109.21 per 100 000). Lung cancer accounted for the majority of cancer-associated mortalities in the province. Attention needs to be focused on women and rural areas due to rapidly increasing incidence and mortality rates for cancer. Furthermore, an effective public health response is imperative, encompassing early screening, diagnosis, and treatment of prevalent cancers in high-risk populations and regions. It's crucial to promote healthy lifestyles among the public through health education.

Performance and effectiveness of hepatocellular carcinoma screening in individuals with HBsAg seropositivity in China: a multicenter prospective study.

Current guidelines recommend hepatocellular carcinoma (HCC) surveillance for at-risk individuals, including individuals with hepatitis B virus infection. However, the performance and survival benefits of annual screening have not been evaluated through multicenter prospective studies in a Chinese population. Between 2017 and 2021, we included 14,426 participants with hepatitis B surface antigen seropositivity in an annual HCC screening study in China using a multicenter prospective design with ultrasonography and serum alpha-fetoprotein. After four rounds of screening and follow-up, the adjusted hazard ratios of death after correction for lead-time and length-time biases for screen-detected cancers at the prevalent and incident rounds were 0.74 (95% confidence interval = 0.60-0.91) and 0.52 (95% confidence interval = 0.40-0.68), respectively. A meta-analysis demonstrated that HCC screening was associated with improved survival after adjusting for lead-time bias. Our findings highlight the 'real-world' feasibility and effectiveness of annual HCC screening in community settings for the early detection of HCC and to improve survival.

Corilagin alleviates LPS-induced sepsis through inhibiting pyroptosis via targeting TIR domain of MyD88 and binding CARD of ASC in macrophages.

Sepsis is a dysregulated systemic inflammatory response caused by infection that leads to multiple organ injury and high mortality without effective treatment. Corilagin, a natural polyphenol extracted from traditional Chinese herbs, exhibits strong anti-inflammatory properties. However, the role for Corilagin in lipopolysaccharide (LPS)-induced sepsis and the molecular mechanisms underlying this process have not been completely explored. Here we determine the effect of Corilagin on LPS-treated mice and use a screening approach integrating surface plasmon resonance with liquid chromatography-tandem mass spectrometry (SPR-LC-MS/MS) to further explore the therapeutic target of Corilagin. We discovered that Corilagin significantly prolonged the survival time of septic mice, attenuated the multi-organ injury and the expression of pyroptosis-related proteins in tissues of LPS-treated mice. In vitro studies revealed that Corilagin inhibited pyroptosis and NLRP3 inflammasome activation in LPS-treated macrophages followed with ATP stimulation, as reflected by decreased levels of GSDMD-NT and activated caspase-1, and reduced ASC specks formation. Mechanistically, Corilagin alleviated the formation of ASC specks and blocked the interaction of ASC and pro-caspase1 by competitively binding with the caspase recruitment domain (CARD) of ASC. Additionally, Corilagin interrupted the TLR4-MyD88 interaction through targeting TIR domain of MyD88, leading to the inhibition of NF-κB activation and NLRP3 production. In addition, Corilagin downregulated genes associated with several inflammatory responses and inflammasome-related signaling pathways in LPS-stimulated macrophages. Overall, our results indicate that the inhibitory effect of Corilagin on pyroptosis through targeting TIR domain of MyD88 and binding the CARD domain of ASC in macrophages plays an essential role in protection against LPS-induced sepsis.