A high-performance liquid chromatography method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was developed to determine the content of 15 amino acids in the medicinal snakes Bungarus Parvus, Agkistrodon, and Zaocys. The results showed that the total amino acid(TAA) content ranged from 277.13 to 515.05 mg·g~(-1), with the top four amino acids in all three species being glutamic acid(Glu), glycine(Gly), aspartic acid(Asp), and lysine(Lys). The essential amino acid(EAA) content ranged from 74.56 to 203.94 mg·g~(-1), with Agkistrodon exhibiting the highest content. The non-essential amino acid(NEAA), semi-essential amino acid(semi-EAA), and medicinal amino acid(MAA) content ranged from 189.06 to 318.23, 12.89 to 33.53, and 179.83 to 342.33 mg·g~(-1), respectively, with Zaocys having the highest content in these categories. Amino acid nutritional value was evaluated using the amino acid ratio(RAA), amino acid ratio coefficient(RCAA), and amino acid ratio coefficient score(SRCAA), and the results indicated that all three medicinal snakes possessed good nutritional value. The amino acid composition was similar across the species, though significant differences in content were observed. Based on these differences, an orthogonal partial least squares-discriminant analysis(OPLS-DA) model was established, which could clearly distinguish between the three medicinal snake species. The key differences in amino acid content included Gly, tyrosine(Tyr), Glu, and serine(Ser), which may be related to the observed clinical application differences among the species. Further research into the mechanisms of these differential amino acids is expected to provide more insights into the clinical application disparities of these three medicinal snake species.
Amino Acids/chemistry* ; Animals ; Nutritive Value ; Chromatography, High Pressure Liquid ; Snakes/classification* ; Bungarus

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Osteoarthritis (OA) is a chronic degenerative joint disease and the most common type of arthritis. It involves almost any joint and can lead to chronic pain and disability. In the late 19th century, Roentgen discovered X-rays, and then began to use radiotherapy to treat tumors. In the 1980s, Luckey thought that low-level radiation (LDRT) might be beneficial to biology, and it was gradually applied to the treatment of some diseases. This paper introduces the epidemiology, risk factors, clinical manifestations and treatment methods of OA, points out that the cartilage injury and the important effect of synovial inflammation in the pathogenesis of OA, namely when the homeostasis of articular cartilage are destroyed, synthetic metabolism and catabolism imbalances, cartilage cells damaged their breakdown products consumed by synovial cells. Synovial cells and synovial macrophages secrete proinflammatory cytokines, metalloproteinases and proteolytic enzymes, leading to cartilage matrix degradation and chondrocyte damage, which aggravates synovial inflammation and cartilage damage, forming a vicious cycle. The possible mechanism and clinical research progress of LDRT in alleviating OA are discussed. LDRT can regulate inflammatory response, inhibit the production of pro-inflammatory cytokines, and promote the production of anti-inflammatory cytokines, thereby achieving anti-inflammatory effect. Studies have shown that after irradiation, the expression of inducible nitric oxide synthase (iNOS) was decreased, the release of reactive oxygen species (ROS) and the production of superoxide were inhibited, the anti-inflammatory phenotype of macrophages was differentiated from M1 to M2, the inflammatory CD8⁺ T cells were transformed into CD4⁺ T cells, and the number of dendritic cells (DC) was significantly reduced. LDRT inhibit the production of proinflammatory factors in leukocytes, reduce their recruitment and adhesion, and down-regulate the expression levels of cell adhesion molecules such as selectin, intercellular adhesion molecule (ICAM) and vascular endothelial cell adhesion molecule (VCAM). LDRT can regulate endothelial cells, stimulate endothelial cells to produce a large amount of TGF-β1, reduce the adhesion of endothelial cells to peripheral blood mononuclear cells (PBMC), and contribute to the anti-inflammatory effect of LDRT. It also exerted anti-inflammatory effects by regulating mitochondrial growth differentiation factor 15 (GDF15). After low-level radiation, the MMP-13 (matrix metalloproteinases-13) and the ADAMTS5 (recombinant a disintegrin and metalloproteinase with thrombospondin-5) decreased, the Col2a1 (collagen type 2) increased in chondrocytes. In the existing clinical studies, most patients can achieve relief of joint pain and recovery of joint mobility after irradiation, and the patients have good feedback on the efficacy. The adverse reactions (acute reactions and carcinogenic risks) caused by LDRT in the treatment of OA are also discussed. During the treatment of OA, a few patients have symptoms such as redness, dryness or itching at the joint skin, and the symptoms are mild and do not require further treatment. Patients are thus able to tolerate more frequent and longer doses of radiotherapy. In general, LDRT itself has the advantages of non-invasive, less adverse reactions, and shows the effect of pain relief and movement improvement in the treatment of OA. Therefore, LDRT has a broad application prospect in the treatment of OA.

Objective:To study the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow of patients with fever of unknown origin.Methods:A total of 465 patients with fever of unknown origin in our hospital from January 2019 to December 2021 were selected as the research objects,which was to reviewed retrospectively the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow.Results:The positive rates of hemophagocytes detected in the three lines decreased group,the two lines decreased group,the one line decreased group,normal group of the three lines and at least one of the three lines increased group were 86.4％,62.1％,38.3％,34.6％and 33.3％,respectively.The number of hemophagocytes per unit area in the three lines decreased group was significantly higher than that in the other four groups(P＜0.001).The number of hemophagocytes per unit area in the two lines decreased group was higher than that in the one line decreased group,normal group of three lines and at least one of the three lines increased group(P＜0.01).There was no significant difference in the number of hemophagocytes per unit area between the group with a decreased number of one line and the other two groups with a normal number of three lines and the group with at least one increased number of three lines(P＞0.05).The missed rates of hemophagocytes in the five groups were 15.78％,22.03％,62.22％,77.78％and 53.84％,respectively.Conclusion:For patients with fever of unknown origin,especially those with obvious decrease in the number of three lines and two lines in peripheral blood cells,which should pay attention to the detection of hemophagocytes in bone marrow.Meanwhile,if the number of three lines was normal even at least one of the three lines increased,the presence of hemophagocytes in the bone marrow slice should be also carefully observed.

Objective:To develop the Economic Toxicity Scale for Kidney Transplantation Patients, and to test the reliability and validity of the scale.Methods:Drawing upon Coleman′s social capital theory and the six subfields associated with economic toxicity put forward by European scholars, the initial version of the scale was developed via expert correspondence consultation and a preliminary survey. This was accomplished by building upon existing literature and conducting semi-structured interviews. A total of 261 cases of kidney transplantation patients from March to October 2022 admitted to the First Affiliated Hospital of Shandong First Medical University were investigated for reliability and validity test.Results:The Economic Toxicity Scale for Kidney Transplantation Patients included 6 dimensions, 31 entries. The total scale had a Cronbach alpha coefficient of 0.910 and the subscale had Cronbach alpha coefficient ranging from 0.798 to 0.943. The retest reliability coefficient for the total scale was 0.948, while the six dimensions ranged from 0.732 to 0.942.Conclusions:The scale demonstrates strong reliability and validity, making it a reliable tool for objectively evaluating the economic toxicity of kidney transplantation patients.

Objective : To explore dental caries-related factors among children aged 3-5 years in Urumqi City and to provide evidence for the etiological study and primary prevention of caries among local children. Methods : A multistage stratified cluster sampling method was used to randomly select children aged 3-5 years in Urumqi City for oral examination, physical examination and questionnaire survey. Data were collected and analyzed by principal component logistic regression using SPSS 23.0 software. Results: Principal component analysis showed that there were seven risk factors whose characteristic root value was greater than 1: oral hygiene habits, family education level, sugar intake, bedtime eating habits, age, gestational age, feeding mode, and cumulative contribution were 66.486% of the total variance. Principal component logistic regression analysis indicated that five factors, namely, oral hygiene habits (OR = 0.795, P = 0.044), family education level (OR = 0.667, P = 0.019), sugar intake (OR = 1.260, P = 0.006), bedtime eating habits (OR = 5.432, P<0.001) and age (OR = 0.676, P = 0.015), were closely related to early childhood caries, and they were statistically significant (P<0.05). Conclusion According to the principal component analysis, oral hygiene habits factor, family education level factor, sugar intake factor, bedtime eating habits factor and age factor were dental caries related factors among 3- to 5-year-old children in Urumqi City.

Bungarus Parvus, a precious animal Chinese medicinal material used in clinical practice, is believed to be first recorded in Ying Pian Xin Can published in 1936. This study was carried out to analyze the names, geographical distribution, morphological characteristics, ecological habits, poisonousness, and medicinal parts by consulting ancient Chinese medical books and local chronicles, Chinese Pharmacopeia, different processing standards of trditional Chinese medicine(TCM) decoction pieces, and modern literatures. The results showed that the earliest medicinal record of Bungarus Parvus was traced to 1894. In 1930, this medicinal material was used in the formulation of Annao Pills. The original animal, Bungarus multicinctus, was recorded by the name of "Bojijia" in 1521. The morphological characteristics, ecological habits, and poisonousness of the original animal are the same in ancient and modern records. The geographical distribution is similar between the ancient records and modern documents such as China Medicinal Animal Fauna. The dried body of young B. multicinctus is used as Bungarus Parvus, which lack detailed references. As a matter of fact, it is still inconclusive whether there are differences between young snakes and adult snakes in terms of active ingredients, pharmacological effects, and clinical applications. This study clarified the medicinal history and present situation of Bungarus Parvus. On the basis of the results, it is suggested that systematic comparison on young and adult B. multicinctus should be carried out to provide references for revising the medicinal parts of B. multicinctus.
Animals ; Bungarus ; Snakes ; China ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal

Artemisiae Argyi Folium is commonly used in clinical practice. Artemisiae Verlotori Folium, the dried leaves of Artemisia verlotorum, is often used as a folk substitute for Artemisiae Argyi Folium in Lingnan area. In this study, gas chromatography-triple quadrupole mass spectrometry(GC-MS) was used to detect the volatile oil components of 27 samples of Artemisiae Verlotori Folium and 13 samples of Artemisiae Argyi Folium, and the volatile components were compared between the two species. The internal standard method was combined with multi-reaction monitoring mode(MRM) to determine the content of six major volatile components. Hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the content data. The results showed that the Artemisiae Argyi Folium samples had higher content and more abundant volatile oils than the Artemisiae Verlotori Folium samples. Artemisiae Argyi Folium mainly had the components with lower boiling points, while Artemisiae Verlotori Folium mainly had the components with higher boiling points. Terpenoids were the main volatile components in Artemisiae Verlotori Folium(mainly sesquiterpenoids) and Artemisiae Argyi Folium(monoterpenoids). In addition, Artemisiae Argyi Folium had higher content of oxygen-containing derivatives than Artemisiae Verlotori Folium. Furthermore, the stoichiometric analysis showed that the two species could be distinguished by both HCA and OPLS-DA, indicating that the volatile components of the two were significantly different. This study can provide a scientific basis for the quality evaluation and data support for the local rational application of Artemisiae Verlotori Folium in Lingnan.
Gas Chromatography-Mass Spectrometry ; Chemometrics ; Oils, Volatile ; Drugs, Chinese Herbal ; Plant Leaves ; Artemisia

Objective:To investigate the risk factors of early neurological deterioration (END) in patients with minor ischemic stroke caused by large vessel occlusion (LVO) and the impact of rescue endovascular thromboectomy (REVT) on clinical outcomes of patients with END at discharge.Methods:Consecutive patients with acute minor ischemic stroke caused by LVO within 24 h of onset in the Third Affiliated Hospital, Soochow University from January 2021 to March 2023 were retrospectively enrolled. Minor ischemic stroke was defined as baseline National Institute of Health Stroke Scale (NIHSS) score ≤5 at admission. END was defined as an increase of ≥4 in the NIHSS score within 24 h after the best medical management. The modified Rankin Scale was used to evaluate the clinical outcomes of patients with END at discharge. 0-2 was defined as a good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for END and the impact of REVT on clinical outcomes in patients with END. Results:A total of 75 patients with minor ischemic stroke caused by LVO were included, of which 31 (41.3%) developed END and 13 (41.9%) underwent REVT after END. Multivariate logistic regression analysis showed that internal carotid artery occlusion was an independent risk factor for END (odds ratio 4.304, 95% confidence interval 1.213-15.270; P=0.024), and REVT was an independent protective factor for good outcomes in patients with END (odds ratio 0.068, 95% confidence interval 0.006-0.774; P=0.030). Conclusions:The incidence of END is higher in patients with minor ischemic stroke caused by LVO, and internal carotid artery occlusion is an independent risk factor for the occurrence of END. Providing REVT after END may improve the clinical outcomes of patients with END at discharge.

Objective: To investigate the association between chronic lung diseases and the risk of lung cancer. Methods: Using UK Biobank (UKB) survey data, 472 397 participants who had not previously been diagnosed with cancer and whose self-reported sex was consistent with their genetic sex were studied. Information on the prevalence of previous chronic lung diseases, general demographic characteristics and the prevalence of lung cancer was collected using baseline questionnaires and national health system data. The multivariate Cox proportional risk regression model was used to analyze the association between four previous chronic lung diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial pulmonary disease) and the risk of lung cancer. A total of 458 526 participants with genotype data in the observational study were selected as research objects, and the closely related and independent genetic loci with four chronic lung diseases were selected as instrumental variables, and the association between four chronic lung diseases and the risk of lung cancer was analyzed by Mendelian randomization (MR). The dose-response relationship between genetic risk score and the risk of lung cancer in different chronic lung diseases was evaluated using a restricted cubic spline function. Results: The age [M (Q₁, Q₃)] of the subjects was 57 (50, 63) years old, and there were 3 516 new cases of lung cancer (0.74%) during follow-up. The multivariate Cox proportional hazard regression model analysis showed that previous chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, about 1.61 (1.49-1.75) and 2.61 (1.24-5.49), respectively. MR Studies showed that genetically predicted chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, with HR (95%CI) of 1.10 (1.03-1.19) and 1.04 (1.01-1.08), respectively. The results of restricted cubic spline function analysis showed that the risk of lung cancer increased linearly with the increase of genetic risk scores for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (P<0.05). Neither observational studies nor Mendelian randomization analysis found an association between previous asthma or interstitial lung disease and the risk of lung cancer (both P values>0.05). Conclusion: Chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are potential risk factors for lung cancer.
Humans ; Middle Aged ; Mendelian Randomization Analysis ; Biological Specimen Banks ; Lung Neoplasms/genetics* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Asthma/genetics* ; Idiopathic Pulmonary Fibrosis/genetics* ; United Kingdom/epidemiology* ; Genome-Wide Association Study