Lung cancer is still one of the most common malignant tumors in the world. With the increase of its incidence and the development of medical technology, the overall survival of lung cancer patients has significantly extended compared to before. The incidence of brain and meningeal metastases from lung cancer has also been rising year by year, but patients with brain and meningeal metastases from lung cancer have a poor prognosis and a very high mortality rate, and the diagnosis is mainly based on computed tomography (CT), magnetic resonance imaging (MRI) and other imaging examinations. However, the imaging features are diverse and the specificity is low, which makes it easy to be misdiagnosed and missed. Therefore, accurately identifying brain and meningeal metastases and timely targeted treatment is crucial for improving patient prognosis. This paper analyzed the diagnosis and treatment of a case of lung cancer with no obvious recurrence and metastasis in nearly 7-year long-term follow-up after radical lung cancer surgery, but the patient with abnormal behavior, impaired consciousness and epilepsy in the past 5 months, and multiple punctate calcifications in the brain found by head CT and MRI. This paper consider that the patient's mental and behavioral symptoms were caused by brain and meningeal metastasis of lung cancer after excluding infectious disease and ineffective treatment of autoimmune encephalitis, and further pathological biopsy and genetic detection confirmed the diagnosis of metastatic lung adenocarcinoma with epidermal growth factor receptor (EGFR) L858R gene mutation, and the patient's symptoms were significantly improved after targeted therapy by Osimertinib. This paper also searched the relevant literatures of brain calcifications in databases such as China National Knowledge Infrastructure (CNKI), Wanfang, UpToDate, PubMed, etc., and found that intracerebral calcifications exist in a variety of diseases, including infectious, genetic and neurodegenerative diseases, vascular diseases, metabolic diseases and tumors. However, brain calcification in brain and meningeal metastases are often underestimated, and the consequent risk is misdiagnosis and delayed treatment. Therefore, brain and meningeal metastases manifested as brain calcification should not be ignored in patients with a history of previous tumors.
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Humans ; Lung Neoplasms/pathology* ; Brain Neoplasms/diagnostic imaging* ; Meningeal Neoplasms/diagnostic imaging* ; Calcinosis/diagnostic imaging* ; Male ; Middle Aged ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Senecavirus A (SVA) is a major viral pathogen causing disease in pigs, and effective monitoring of SVA infection is critical for disease control. In this study, we aimed to develop a reliable ELISA method for rapidly detecting neutralizing antibodies against SVA. We used HEK293F cells to express an SVA-specific porcine Fab antibody and verified the biological activity of the Fab antibody by indirect ELISA, immunofluorescence assay, virus neutralization test, and Western blotting. The Fab antibody was biotinylated and used as a competitive antibody to establish a competitive ELISA (C-ELISA) for detecting neutralizing antibodies against SVA. We then evaluated the C-ELISA in terms of sensitivity, specificity, repeatability, and result agreement rate with the VNT. The results showed that we successfully prepared an SVA-specific porcine Fab antibody, which showed high affinity for SVA. We named this antibody 1M33Fab and designated it as Bio-1M33Fab after biotin labeling. The assay conditions were optimized as follows: the coating concentration of SVA particles being 1 μg/mL, the working concentration of Bio-1M33Fab being 0.5 μg/mL, the optimal serum dilution of 1:10, and the optimal dilution of enzyme-labeled avidin being 1:30 000. At a percent inhibition (PI) of 47%, the assay demonstrated the highest sensitivity (96.88%) and specificity (100%), with no cross-reactivity observed with the positive sera of major porcine viral diseases. The intra-assay coefficient of variation ranged from 1.12% to 7.34%, while the inter-assay coefficient of variation ranged from 1.10% to 8.97%, indicating good repeatability. In the detection of 224 clinical pig serum samples, C-ELISA and VNT showed a result agreement rate of 93.75%. In conclusion, we successfully develop a C-ELISA method for detecting neutralizing antibodies against SVA by using a porcine-derived Fab antibody, which lays a foundation for the development of detection kits.
Animals ; Swine ; Antibodies, Neutralizing/immunology* ; Enzyme-Linked Immunosorbent Assay/methods* ; Immunoglobulin Fab Fragments/immunology* ; Antibodies, Viral/immunology* ; Picornaviridae/immunology* ; Humans ; HEK293 Cells ; Swine Diseases/diagnosis* ; Picornaviridae Infections/diagnosis*

ObjectiveTo explore the possible mechanism of Chuanxiong （Rhizoma Chuanxiong） & Tianma （Rhizoma Gastrodiae） herbal pair in treating migraines based on AMP-activated protein kinase （AMPK）/transient receptor potential A1 channel （TRPA1） pathway. MethodsForty-eight healthy male SD rats were randomly divided into control group， model group， and Chuanxiong Tianma medication group， with 16 rats in each group. The control group and model group were given 10 ml/kg of normal saline by gavage， while the Chuanxiong Tianma medication group was given 0.675 g/kg of Chuanxiong Tianma herbal pair by gavage， once daily for 8 consecutive days in both groups. Migraime model was performed before the last administration， with subcutaneous injection of 10 ml/kg of normal saline in the control group， and subcutaneous injection of 10 ml/kg of nitroglycerin in the model group and Chuanxiong Tianma medication group. The Von Frey filament was used to measure the periorbital mechanical pain threshold of rats. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of calcitonin gene-related peptide （CGRP） in rat serum and cerebrospinal fluid. The nitric oxide （NO） assay kit was used to determine the NO level in serum and cerebrospinal fluid. RT-PCR was usedto detect the mRNA expression levels of immediate-early genes in the trigeminal ganglion of rats （c-Fos）， CGRP， transient receptor potential V1 channel （TRPV1）， AMPK alpha subunit （PRKAA）， and TRPA1. Immunofluorescence was used to detect the number of c-Fos-positive cells in the trigeminal cervical complex （TCC） and the protein expression levels of phosphorylated AMPK （pAMPK） and TRPA1 in the trigeminal ganglion. ResultsCompared to those in the control group， the mechanical stimulation threshold and pAMPK protein expression in the model group decreased， while the levels of CGRP and NO in serum， c-Fos， CGRP， TRPV1 and TRPA1 mRNA levels in the trigeminal ganglion， TRPA1 protein expression， and the number of c-Fos-positive cells in the TCC significantly increased （P＜0.05）. Compared to those in the model group， the mechanical stimulation threshold and pAMPK protein expression in the Chuanxiong Tianma medication group significantly increased， while the levels of CGRP and NO in serum， c-Fos， CGRP， TRPV1 and TRPA1 mRNA levels in the trigeminal ganglion， TRPA1 protein expression， and the number of c-Fos-positive cells in the TCC significantly decreased （P＜0.05）. ConclusionChuanxiong Tianma herbal pair may improve migraine symptoms by regulating the AMPK/TRPA1 pathway in the trigeminal ganglion and increasing the mechanical pain threshold.

ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group， Shenqi Jianxin Formula group， MCC950 group and the combination group （Shenqi Jianxin Formula plus MCC950）， with 8 rats in each group. In Shenqi Jianxin Formula group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （P＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in Shenqi Jianxin Formula group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （P＜0.05）. Compared with Shenqi Jianxin Formula group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （P＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （P＜0.05）. ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.

Objective:To explore the application effect of nursing intervention based on the mindfulness-attention-acceptance theory in children with bronchopneumonia.Methods:Totally 127 children with bronchopneumonia admitted to the First Affiliated Hospital of Xinjiang Medical University from January to July 2023 were selected by convenience sampling. They were randomly divided into a control group and an observation group according to a random number table. The control group (63 cases) received routine nursing intervention, while the observation group (64 cases) received nursing intervention based on the mindfulness-attention-acceptance theory in addition to the routine nursing intervention. The improvement in psychological resilience, coping styles, and emotional behaviors of the two groups were compared before and after the intervention.Results:After the intervention, the scores of all dimensions of the Psychological Resilience Scale in both groups were higher than that before the intervention, with the observation group scoring higher than the control group ( P<0.05). The observation group scored higher on all dimensions of positive coping and lower on all dimensions of negative coping compared to the control group ( P<0.05). The prosocial behavior dimension score of the observation group was higher than that of the control group, while the scores of emotional symptoms, conduct problems, and hyperactivity-inattention dimensions were lower than those of the control group ( P<0.05) . Conclusions:The application of nursing intervention based on the mindfulness-attention-acceptance theory in children with bronchopneumonia can effectively improve their psychological resilience, coping styles, and emotional behaviors.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

This study explores the effects and possible mechanisms of nuclear factor E2 related factor 2 (NRF2) on ovarian granulosa cells, providing a scientific basis to prevent premature ovarian failure. An ovarian cell injury model was constructed by treating human ovarian granulosa cell (KGN cell) with 4-Vinylcyclohexene dioxide (VCD). Firstly, KGN cells were treated with different concentrations of VCD, and cell counting kit 8 (CCK-8) was used to detect ovarian cell proliferation. After determining IC 50 by CCK8, the levels of estradiol and progesterone in the cell supernatant were detected using enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) assay kit was used to detect the content of ROS in ovarian cells, real-time fluorescence quantitative polymerase chain reaction (qRT PCR) was used to detect the mRNA expression level of NRF2, and Western blot was used to detect the protein expression level of NRF2. Further, NRF2 silence (siNRF2) and overexpression (NRF2-OE) cell models were constructed through lentivirus transfection, and the effects of regulating NRF2 on VCD treated cell models were investigated by detecting hormone levels, oxidative stress indicators (ROS, SOD, GSH-Px), and autophagy (LC3B level). The results showed that VCD intervention inhibited the proliferation of ovarian granulosa cells in a time-dependent and dose-dependent manner ( F>100, P<0.05), with an IC 50 of 1.2 mmol/L at 24 hours. After VCD treatment, the level of estradiol in the cell supernatant decreased from (56.32±10.18) ng/ml to (24.59±8.75) ng/ml ( t=5.78, P<0.05). Progesterone decreased from (50.25±7.03) ng/ml to (25.13±6.67) ng/ml ( t=6.54, P<0.05). After VCD treatment, the SOD of cells decreased from (44.47±7.71) ng/ml to (30.92±4.97) ng/ml ( t=3.61, P<0.05). GSH-Px decreased from (68.51±10.17) ng/ml to (35.19±6.59) ng/ml ( t=5.73, P<0.05). Simultaneously accompanied by an increase in autophagy and a decrease in NRF2. This study successfully constructed KGN cell models that silenced NRF2 and overexpressed NRF2. Subsequently, this study treated each group of cells with VCD and found that the cell proliferation activity of the siNRF2 group was significantly reduced ( t=8.37, P<0.05), while NRF2-OE could reverse the cell activity damage caused by VCD ( t=3.37, P<0.05). The siNRF2 group had the lowest level of estradiol ( t=5.78, P<0.05), while NRF2-OE could reverse the decrease in cellular estradiol levels caused by VCD ( t=5.58, P<0.05). The siNRF2 group had the lowest progesterone levels ( t=3.02, P<0.05), while NRF2-OE could reverse the decrease in cellular progesterone levels caused by VCD ( t=2.41, P<0.05). The ROS level in the siNRF2 group was the highest ( t=2.86, P<0.05), NRF2-OE could reverse the increase in ROS caused by VCD ( t=3.14, P<0.05), the SOD enzyme content in the siNRF2 group was the lowest ( t=2.98, P<0.05), and NRF2-OE could reverse the decrease in SOD enzyme content caused by VCD ( t=4.72, P<0.05). The GSH-Px enzyme content in the siNRF2 group was the lowest ( t=3.67, P<0.05), and NRF2-OE could reverse the decrease in antioxidant enzyme content caused by VCD ( t=2.71, P<0.05). The LC3B level was highest in the siNRF2 group ( t=2.45, P<0.05), and NRF2-OE was able to reverse the LC3B elevation caused by VCD ( t=9.64, P<0.05). In conclusion, NRF2 inhibits ROS induced autophagy, thereby playing a role in reducing ovarian granulosa cell damage, which may be a potential target for premature ovarian failure.

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

Objective To analyze the status of occupational disease hazards in Shantou City for 2019 to 2022 and propose corresponding management measures. Methods Technical reports on various occupational-disease-specific activities in Shantou City from 2019 to 2022 were collected and the data were comprehensively analyzed. Results Among the 3 066 enterprises surveyed in the 2020 occupational disease hazard investigation in Shantou City, occupational hazards were reported in 2 982 enterprises (accounting for 97.3%), with 2 955 being small and micro enterprises, accounted for 99.1%(2 955/2 982). The exposure rate of occupational hazards was 58.7% (42 894/73 054) among workers in the surveyed enterprises, with dust and noise exposure rates of 59.7% and 77.8%, respectively. The reported rate of occupational disease hazard projects by employers, regular detection rate of workplace occupational hazards, detection rate of occupational medical examination among workers, and occupational health training rate of key responsible personnel and occupational health management staff were 8.4%, 1.4%, 2.4%, and 4.3%, respectively. The results of occupational hazards monitoring of workplace in key industries from 2019 to 2022 showed that noise had the highest rate of exceeding national standards workplace, followed by silica dust, accounting for 34.2% and 13.8%, with the on-site exceedance rate of 32.2% and 10.0%, respectively. From 2019 to 2022, 31 suspected occupational disease cases were identified in key occupational disease monitoring, including 27 suspected cases of occupational pneumoconiosis and four suspected cases of occupational noise-induced deafness. Conclusion The workers in Shantou City have a high exposure rate to occupational hazards, and the occupational health management level of employers remains low, with noise and silica dust being the most severe occupational hazards. It is essential to improve technical support and service system development for occupational disease prevention and treatment, strengthen supervision and management in key industries and positions, explore occupational health assistance mechanisms for small and micro enterprises, and enforce employers' responsibility in occupational disease prevention to protect workers' occupational health and safety.