The etiology of tumors is complex and influenced by multiple factors, including the host and environmental conditions. Allergy is primarily driven by the immune response of helper T cell 2 (Th2). Research has shown that the Th2 immune response is closely related to tumors, which is specifically manifested through Th2 antibodies, allergy-related effector cells and mediators within the tumors, as well as tumor immune-related functions. This internal interaction mechanism will increase the complexity and challenges associated with the clinical diagnosis and treatment of tumors and allergy. The formation of allergic constitution is shaped by both congenital and acquired factors, and its physical state is closely linked to the occurrence and progression of allergic diseases. Therefore, this paper aims to explore the relationship between tumors and allergic reactions from the perspective of traditional Chinese medicine (TCM) constitution theory. Based on the four basic principles of the TCM constitution, including endowment inheritance theory, environment constraint theory, body-spirit composition theory, and life process theory, this exploration will focus on four aspects: genetic factors and internal disease causes, inflammatory environments and functional regulation, psychological disorders and emotional pathogenesis, as well as age structure and disease risk. Furthermore, from the perspective of constitution-disease relation of chronic disease prevention, this paper will discuss the significant importance of adjusting allergic constitution to improve both subjective symptoms and objective indicators of allergic reactions in tumor patients.

ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C （SFTPC） and lung injury induced by chronic intermittent hypoxia （CIH） and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups： a normoxia group， a CIH group， and low-， medium-， and high-dose Buzhong Yiqitang groups， with eight mice in each group. During the modeling， mice in the normoxia group were housed under standard oxygen concentrations， while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session， mice in the low-， medium-， and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses （8.1， 16.2， 32.4 g·kg^-1·d^-1 of crude drug， respectively）， while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung tissue were evaluated using hematoxylin-eosin （HE） staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. Protein expression of SFTPC， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， protein kinase R-like endoplasmic reticulum kinase （PERK）， phosphorylated PERK （p-PERK）， eukaryotic initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， activating transcript factor 4 （ATF4）， and CCAAT/enhancer-binding protein homologous protein （CHOP） in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group， mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels increased， while SFTPC expression in lung tissue was reduced （P<0.05， P<0.01）. The rate of apoptotic cells in lung tissue increased， and the expression of endoplasmic reticulum stress markers p-PERK， p-eIF2α， ATF4， and CHOP was upregulated （P<0.05， P<0.01）. Compared with the CIH group， Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels were decreased， and lung tissue SFTPC expression was recovered （P<0.05， P<0.01）. The apoptotic rate of lung tissue cells was significantly reduced， with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression （P<0.05， P<0.01）. Activation and expression of p-PERK， p-eIF2α， ATF4， and CHOP were also decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion， which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.

Epilepsy, which leads to an enduring high tendency to generate epileptic seizures, is a neurological disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to abnormal synchronous neuronal discharges. Patients with epilepsy are usually comorbid with various sleep disorders, such as restless leg syndrome/periodic limb movement disorder (RLS/PLMD), chronic insomnia and narcolepsy. Frequent seizures may increase the risk of suffering from sleep disorders; conversely, poor control of sleep disorders exacerbates epilepsy. This review discusses common types of sleep disorders in patients with epilepsy, reveals potential mechanisms, and introduces new advances in the treatment of comorbidity between epilepsy and sleep disorders. The aim is to provide an overview of the close interactions between epilepsy and sleep disorders, providing new ideas and experiences for more effective treatment of sleep disorders and improving the prognosis of patients with epilepsy.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

OBJECTIVE: To investigate whether adding 1 transverse screw (TS) to the triangular parallel cannulated screw (TPCS) fixation has a mechanical stability advantage for Pauwels type Ⅲ femoral neck fractures by conducting finite element analysis on four internal fixation methods. METHODS: Based on CT data of a healthy adult male volunteer's femur, three Pauwels type Ⅲ femoral neck fracture models (Pauwels angle 70°, Pauwels angle 80°, and Pauwels angle 70° combined with bone defect) were constructed using Mimics 21.0 software and SolidWorks 2017 software. Four different internal fixation models were built at the same time, including TPCS, TPCS+TS, three cross screws (TCS), and TPCS+medial buttress plate (MBP). The mechanical stability of different models under the same load was compared by finite element analysis. RESULTS: The femoral model established in this study exhibited a maximum stress of 28.62 MPa, with relatively higher stress concentrated in the femoral neck. These findings were comparable to previous studies, indicating that the constructed femoral finite element model was correct. The maximum stress of internal fixation in finite element analysis showed that TCS was the lowest and TPCS+MBP was the highest in Pauwels angle 70° and 80° models, while TPCS+TS was the lowest and TCS was the highest in Pauwels angle 70° combined with bone defect model. The maximum displacement of internal fixation in each fracture model was located at the top of the femoral head, with TCS having the highest maximum displacement of the femur. The maximum stress of fracture surface in finite element analysis showed that TCS was the lowest and TPCS was the highest in the Pauwels angle 70° model, while TPCS+MBP was the lowest and TPCS/TCS were the highest in the Pauwels angle 80° model and the Pauwels angle 70° combined with bone defect model, respectively. The maximum displacement of fracture surfece analysis showed that TPCS+MBP was the lowest and TCS was the highest in Pauwels angle 70° and 80° models, while TPCS+TS was the lowest and TCS was the highest in Pauwels angle 70° combined with bone defect model. CONCLUSION For Pauwels type Ⅲ femoral neck fractures, the biomechanical stability of TPCS+TS was superior to that of TPCS alone and TCS, but it has not yet reached the level of TPCS+MBP.
Finite Element Analysis ; Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Screws ; Fracture Fixation, Internal/instrumentation* ; Male ; Bone Plates ; Stress, Mechanical ; Biomechanical Phenomena ; Tomography, X-Ray Computed ; Adult ; Femur Neck/surgery*

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0-10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

Peanut, a major economic and oil crop known for the high protein and oil content, is extensively cultivated in China. Peanut plants have the ability to form nodules with rhizobia, where the nitrogenase converts atmospheric nitrogen into ammonia nitrogen that can be utilized by the plants. Analysis of nodule fixation is of positive significance for avoiding overapplication of chemical fertilizer and developing sustainable agriculture. In this study, AhNIGT1.2, a member of the NIGT family predominantly expressed in peanut nodules, was identified by bioinformatics analysis. Subsequent spatiotemporal expression analysis revealed that AhNIGT1.2 was highly expressed in nodules and showed significant responses to high nitrogen, low nitrogen, high phosphorus, low phosphorus, and rhizobia treatments. Histochemical staining indicated that the gene was primarily expressed in developing nodules and at the connection region between mature nodules and peanut roots. The fusion protein AhNIGT1.2-GFP was located in the nucleus of tobacco epidermal cells. The AhNIGT1.2-OE significantly increased the number of peanut nodules, while AhNIGT1.2-RNAi reduced the number of nodules, which suggested a positive regulatory role of AhNIGT1.2 in peanut nodulation. The AhNIGT1.2-OE in roots down-regulated the expression levels of NRT1.2, NRT2.4, NLP1, and NLP7, which indicated that AhNIGT1.2 influenced peanut nodulation by modulating nitrate transport and the expression of NLP genes. The transcriptome analysis of AhNIGT1.2-OE and control roots revealed that overexpressing AhNIGT1.2 significantly enriched the differentially expressed genes associated with nitrate response, nodulation factor pathway, enzymes for triterpene biosynthesis, and carotenoid biosynthesis. These findings suggest that AhNIGT1.2 play a key role in peanut nodulation by regulating nitrate transport and response and other related pathways. This study gives insights into the molecular mechanisms of nitrogen and phosphorus in regulating legume nodulation and nitrogen fixation, and sheds light on the development of legume crops that can efficiently fix nitrogen in high nitrogen environments.
Arachis/physiology* ; Nitrates/metabolism* ; Plant Proteins/physiology* ; Transcription Factors/metabolism* ; Plant Root Nodulation/physiology* ; Gene Expression Regulation, Plant ; Root Nodules, Plant/metabolism* ; Nitrogen Fixation