The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPARγ, AKT1, PTG2 and other targets. The lipid metabolism and atherosclerotic pathway was verified using human hl-7702 hepatocytes. This study preliminarily identified the potential pharmacodynamic components of Guanxin Qiwei tablets in the treatment of AS diseases and predicted their pathways of action, and verified the relationship between regulating lipid metabolism and atherosclerosis of Guanxin Qiwei tablets in vitro, providing a reference for the further study of the pharmacodynamic material basis and mechanism of action of this prescription. This experiment was approved by the Medical Ethics Committee of Inner Mongolia Medical University (No. YKD202401262).

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective: To investigate the clinical characteristics of children with allergic diseases suffering from SARS-CoV-2 Omicron variant strains. Methods: This was a cross-sectional study. A total of 43 pediatric patients with allergic diseases infected by SARS-CoV-2 from April 25, 2022 to June 8, 2022 in Shanghai Jiao Tong University School of Medicine were selected as the allergic disease group, while 114 cases without underlying diseases and 16 cases with other underlying diseases were selected as control groups diagnosed at the same period. Clinical data including clinical features, laboratory tests, duration of hospitalization, and the time to negative turn of novel coronavirus nucleic acid were collected and analysed. Kruskal-Wallis H test, chi-square test or Fisher exact test were used for comparison among three groups. Results: Among the 43 patients with allergic diseases, 28 were males and 15 were females, with an age of 4.4 (2.1, 8.2) years on admission, including 32 mild cases and 11 common cases. The allergic disease group included 20 cases (46.5%) of atopic dermatitis and eczema, followed by 14 cases (32.6%) of rhinitis, 8 cases (18.6%) of food allergies, 7 cases (16.3%) of asthma, 4 cases (9.3%) of allergic conjunctivitis and 2 cases (4.7%) of drug allergy. Among the 114 cases without underlying diseases, 57 were males and 57 were females, with an age of 2.8 (1.2, 5.6) years on admission, including 93 mild cases and 21 common cases. Among the 16 cases with other underlying diseases, 9 were males and 7 were females, with an age of 3.0 (2.6, 10.8) years on admission, including 13 cases mild and 3 cases common cases. Children with allergic diseases had higher frequency of sore throat and vomiting than those without underlying diseases (10 cases (23.3%) vs.9 cases (7.9%), 14 cases (32.6%) vs. 11 cases (9.6%), χ²=6.93, 12.24, both P<0.05). The lymphocyte count of patients with allergic disease was lower than those without underlying disease (1.1 (0.7,1.7)×10⁹ vs. 1.6 (1.1,2.7)×10⁹/L, H=-28.00,P=0.005). There were no significant differences in age, gender, typing of SARS-CoV-2, the duration of hospitalization, cycle threshold values of SARS-CoV-2 and the time to negative turn of novel coronavirus nucleic acid among the three groups (all P>0.05). Conclusions: Children with allergic diseases may suffer from sore throat and vomiting more frequently when infected with SARS-CoV-2 Omicron variant. The combination of allergic diseases hardly influenced the disease course of SARS-CoV-2 in children.
Male ; Female ; Humans ; Child ; SARS-CoV-2 ; Cross-Sectional Studies ; COVID-19 ; China/epidemiology* ; Food Hypersensitivity ; Pharyngitis

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Background Previous studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet. Objective To evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers. Methods A total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q₁-Q₄) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models. Results The workers' medians (P₂₅, P₇₅) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L^-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q₁ group, blood aluminum in the Q₂, Q₃, or Q₄ group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, P_trend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, P_trend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, P_trend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (P_trend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (P_trend>0.05). Conclusion Occupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.

Objective To prepare a rabbit anti-mouse coiled-coil domain containing 189 (Ccdc189) polyclonal antibody. Methods The pET-28a-Ccdc189 prokaryotic expression plasmid was constructed and transformed into E.coli BL21. IPTG was used to induce the expression of Ccdc189 prokaryotic protein. Adult male New Zealand rabbits were immunized with purified recombinant protein to obtain rabbit anti-mouse Ccdc189 polyclonal antibody. The specificity of the polyclonal antibody was identified by Western blot analysis, indirect ELISA and immunofluorescence histochemical staining. Results The pET-28a-Ccdc189 recombinant plasmid was successfully constructed and the expression of the Ccdc189 recombinant protein was induced. ELISA revealed that the titer of the polyclonal antibody was 1:1 000 000. Western blot and immunofluorescence staining demonstrated that the Ccdc189 polyclonal antibody could specifically identify the Ccdc189 prokaryotic protein and the Ccdc189 protein in adult wild-type mouse testis. Conclusion A polyclonal antibody with high specificity against mouse Ccdc189 was successfully created.
Rabbits ; Male ; Animals ; Mice ; Antibody Specificity ; Antibodies ; Enzyme-Linked Immunosorbent Assay ; Blotting, Western ; Recombinant Proteins ; Escherichia coli/genetics*

The effective implementation of curricular ideology should be vigorously promoted in the training process of postgraduate students in critical care medicine.The clinical practice of critical care medicine contains a large number of ideological elements.In the process of teaching,teachers need to explore the ideological and political elements closely related to critical care medicine,mainly including:correct value of life,self-supervision spirit,communication and collaboration ability,healer's benevolence,craftsmanship,honesty and integrity in medical practice,as well as the supremacy of the country and the people,and so on.In the process of implementing curriculum ideological and political teaching,teachers are required to continuously improve their professionalism and ethics,improve their teaching methods,and set a good example in their clinical work.In order to better implement the curriculum ideological and political education,it is necessary to establish a perfect teaching system and a unified curriculum ideological and political education material library.