Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the expression of CD19/CD73 in chronic lymphocytic leukemia (CLL) and its correlation with clinical features. METHODS: The clinical data of 60 CLL patients and 40 healthy volunteers (control group) from January 2022 to November 2023 were retrospectively analyzed. The levels of CD19 and CD73 in peripheral blood of CLL patients were measured by flow cytometry. Kaplan-Meier method was used for survival analysis. RESULTS: The hemoglobin (Hb) and CD19/CD73 levels in CLL group were significantly lower than those in control group, while CD19, CD73 and β₂-MG were significantly higher (all P <0.001). According to ROC curve analysis, the AUC value of CD19/CD73 for CLL diagnosis was 0.980 (95%CI : 0.949-1.000, P <0.05), the specificity was 92.50%, and the sensitivity was 98.30%. The CD19/CD73 level of CLL patients with splenomegaly was significantly lower than those without splenomegaly (P <0.01). There was no significant correlation between CD19/CD73 and Hb in CLL patients ( r =0.056, P >0.05). CD19/CD73 was positively correlated with β₂-MG ( r =0.837, 95%CI : 0.740 2-0.899 6, P <0.01). According to the median value (12.84) of CD19/CD73, the patients were divided into high and low expression groups. Kaplan-Meier survival analysis showed that the overall survival rate and progression-free survival rate at 18^th month in the low expression group were 87.08% and 93.25%, while those in the high expression group were 96.41% and 99.90%, respectively (both P <0.05). CONCLUSION The level of CD19/CD73 is low in CLL patients, which can be used as an auxiliary index for clinical diagnosis of CLL. CD19/CD73 is closely related to splenomegaly in CLL patients. Low expression of CD19/CD73 predicts poor prognosis.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism* ; 5'-Nucleotidase/metabolism* ; Antigens, CD19/metabolism* ; Retrospective Studies ; Male ; Female ; Prognosis ; Middle Aged ; Aged ; Adult ; GPI-Linked Proteins

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.

The detection of cancer markers is of great significance for the early diagnosis and subsequent treatment of cancer.However,the existing traditional detection methods have some limitations,especially in the early stages of cancer,thus is often difficult to detect in a timely and accurate manner.As an efficient detection technique,electrochemical sensors can meet the requirement of accurate detection of various cancer markers,provide strong support for early diagnosis of cancer,and have broad application prospects.MXene is a new two-dimensional material,which is widely used in electrochemical sensors because of its unique properties such as high electron transfer ability,high conductivity,large specific surface area,good biocompatibility and hydrophilicity and abundant surface chemical groups,etc.This paper reviewed the applications of electrochemical biosensors based on MXene composites in cancer marker detection in recent years,introduced the function of MXene in electrochemical biosensor,and discussed challenges and future development trends of MXene in the early diagnosis of cancer,aiming to provide reference for early detection of cancer.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

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.