Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Objective To investigate the mechanism by which miR-148a affects M2 macrophage polarization and inhibits liver cancer cell proliferation through Wnt3a/β-catenin. Methods The mRNA expression levels of miR-148a, CD206 and interleukin-10 (IL-10) in tumor tissues and adjacent non-tumor liver tissues of 84 patients with liver cancer were detected by real-time quantitative PCR. THP-1 cells were separated into blank group (conventional culture), M2 group (200 nmol/L phorbol ester, 20 ng/mL IL-4, 20 ng/mL IL-13), M2 combined with negative control (miR-NC) group (transfected with miR-NC on the basis of M2 group), M2 combined with miR-148a mimics (transfected with miR-148a mimics on the basis of M2 group) group, M2 combined with miR-148a mimics combined with Wnt3a (treated with 100 μg/L Wnt3a on top of M2 combined with miR-148a mimics group) group. The proliferation of HuH7 cells was detected by CCK-8 and EdU methods. Apoptosis and M2 macrophage marker CD206 was detected by flow cytometry. The level of IL-10 in cell supernatant was detected by chemiluminescence method; The mRNA levels of miR-148a, CD206 and IL-10 were detected by real-time quantitative PCR. The protein levels of Wnt3a and β-catenin were detected by Western blot. Results The expressions of CD206, IL-10 mRNA, Wnt3a and β-catenin in tumor tissue were higher than those in non-tumor liver tissues, and the miR-148a level was decreased. The mRNA expression of M2 macrophage markers CD206 and IL-10 were significantly increased. Compared with the blank group, the OD450 value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were increased in M2 group, while the apoptotic rate and miR-148a level were decreased. Compared with M2 group and M2 combined with miR-NC group, the OD₄₅₀ value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were decreased in M2 combined with miR-148a mimics group, while the apoptotic rate and miR-148a level were increased. Wnt3a reversed the inhibitory effect of miR-148a overexpression on the proliferation of liver cancer cells. Conclusion Overexpression of miR-148a inhibits M2 polarization of macrophages and prevents the proliferation of liver cancer cells, which may be related to the inhibition of the Wnt3a/β-catenin pathway.
Humans ; MicroRNAs/metabolism* ; Wnt3A Protein/metabolism* ; Liver Neoplasms/metabolism* ; Cell Proliferation/genetics* ; beta Catenin/genetics* ; Macrophages/metabolism* ; Interleukin-10/metabolism* ; Apoptosis/genetics* ; Cell Line, Tumor ; Female ; Male ; Mannose Receptor ; Lectins, C-Type/metabolism* ; Mannose-Binding Lectins/metabolism* ; Middle Aged ; Receptors, Cell Surface/metabolism*

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

Objective To investigate whether levosimendan can inhibit the apoptosis of C2C12 cells induced by lipopolysaccharide(LPS)through the PTEN/Akt pathway.Methods C2C12 cells were randomly divided into four groups:blank control group,control group comprising cells treated with levosimendan only,LPS-treated group,and a group comprising cells pretreated with levosimendan for 24 h a subsequently treated with LPS for 48 h.The survival rate of C2C12 cells was determined via the CCK-8 method,and cell apoptosis was assessed via Hoechst 33342 staining.The mRNA and protein expression levels of PTEN/Akt pathway components were evaluated via RT-qPCR and Western blotting,respectively.C2C12 cells were also transfected with siRNA to knockdown the PTEN gene,and the effect on the protein expression of apoptotic pathway components was determined.Results Levosimendan increased the survival rate and decreased the apoptosis rate of C2C12 cells after LPS treatment.PTEN gene expression was inhibited by siRNA and the mRNA and protein levels of PTEN/Akt signaling pathway components changed correspondingly.Furthermore,the apoptosis rate of C2C12 cells decreased.Conclusion Levosimendan can inhibit LPS-induced C2C12 cell apoptosis via the PTEN/Akt pathway.

The"season-visceral-related"theory originated from Huangdi Neijing,and its content contains the"holism of five viscera"and"correspondence between nature and humans"in the theoretical system of traditional Chinese medicine(TCM).Recently,the prevalence of post-stroke cognitive impairment(PSCI)has gradually increased with the increasing incidence of stroke.TCM believes that PSCI is located in the brain,however,the causative factors such as phlegm,depression,deficiency,and stasis are caused by the lesions of the five zang viscera.Therefore,PSCI can not be treated with the brain alone.Based on the"season-visceral-related"theory,this article discusses the etiology,pathogenesis,and treatment ideas for PSCI from the four seasons and five zang viscera.Xiaoyao Pill was selected as a treatment for patients with qi imbalance in spring to disperse stagnated liver qi to relieve qi stagnation.Tianwang Buxin Dan was selected as a treatment for patients with blood loss and spirit injury in the summer to nourish the blood and calm the heart and brain.Kaixin Powder was selected as a treatment for patients with spleen deficiency and phlegm blockage in late summer to strengthen the spleen,awaken the mind,and remove stasis.Wenfei Jiangzhuo Decoction was selected as a treatment for patients with qi deficiency and spirit departure in autumn to nourish the lungs,reduce turbidity,and nourish the mind.Dihuang Yinzi was selected as a treatment for patients with marrow reduction and internal toxin in winter to expel phlegm and fill the mind.Treating PSCI using the"season-visceral-related"theory reflects the overall concept of TCM and the hypothesis of syndrome differentiation and treatment and provides novel method for treating PSCI.

Objective Pulmonary oxygen poisoning resulting from hyperbaric oxygen,frequently occurs in specialized operations,without any current effective prevention or treatment measures.To elucidate the impact and mechanism of neostigmine(NEO)in combination with anisodamine(ANI)(neoscopolamine)on pulmonary oxygen toxicity.Methods The animal model of pulmonary oxygen poisoning was established.C57BL/6 mice were exposed to 2.5 ATA 99.9%oxygen for 6 h.The control group mice were injected with normal saline ip,while the treatment group mice received injections of ANI(25 mg/kg,ip)and NEO(50 μg/kg,ip).Lung tissues were collected and stained with HE to observe any pathological injuries after exposure.Evans blue stain was utilized to identify lung permeability,wet/dry lung ratio,and protein concentration in the bronchoalveolar lavage fluid(BALF)to assess the lung injury's severity.The modifications in inflammatory factors,oxidative stress indicators,and iron content in lung tissue were assessed.Results The results showed that the 2.5 ATA 99.9%oxygen-exposed group experienced a significant worsening of lung injury,as well as increased lung permeability,lung wet/dry ratio,and protein content in alveolar lavage fluid when compared to the control group.Moreover,mRNA levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,and IFN-γ in the lung tissue of the model group were significantly elevated,while the levels of anti-inflammatory cytokines IL-4 and TGF-β were significantly reduced.The oxidative index MDA also significantly increased,while the antioxidant index GSH significantly decreased.Additionally,the expression of GPX4,a marker of ferroptosis,increased with an increase in iron content.Neoscopolamine treatment successfully reversed those effects.Conclusion The combined use of ANI and NEO had a protective effect on pulmonary oxygen poisoning.Neoscopolamine may inhibit inflammation and oxidative stress by activating the cholinergic anti-inflammatory pathway,thereby reducing the content of free iron in lung tissue and finally inhibiting cell ferroptosis.

Surgery is an important treatment for the anterior mediastinal disease. With the rapid development of minimally invasive techniques, complete resection of the lesion in most patients with thymic disease can be achieved through thoracoscopic surgery. Practice has proved that the three-port resection of anterior mediastinal thymus disease via the subxiphoid approach is an ideal surgical method for the treatment of anterior mediastinal thymic tumors at present, which has strong popularization and popularity and can benefit the patients. The procedure focuses primarily on the anterior and upper mediastinum and can thoroughly expose the anatomy of the mediastinum and both sides, with minimal intraoperative bleeding, high safety, minimal trauma and postoperative pain, and a short hospital stay. It has clear advantages over conventional thoracic open-heart surgery and transversal resection. However, the surgical approach and field of view, and intraoperative precautions of this procedure are completely different from those of previous thoracoscopic procedures, and from the subxiphoid single-port approach adopted by other centers. Based on 10 years of surgical experience at our center, a modular mode of surgical operation has been developed and its procedure has been standardized. This paper will share and discuss relevant operational points and experiences.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

BACKGROUND:Despite unrelated cord blood transplantation is expected to become an important method for treating malignant hematological diseases,the manifestation and clinical characteristics of acute graft-versus-host disease in the gastrointestinal tract still require further in-depth investigation. OBJECTIVE:To analyze the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation. METHODS:A retrospective analysis was conducted on 668 malignant hematological disease patients after unrelated cord blood transplantation who underwent hematopoietic stem cell transplantation subspecialty in the Department of Hematology,First Affiliated Hospital of University of Science and Technology of China from December 2016 to December 2020.Among them,clinical data of 138 patients with intestinal acute graft-versus-host disease were analyzed,including 76 males and 62 females,with a median age of 13(1-62)years.All patients were treated with a myeloablative regimen(without antihuman thymocyte globulin)and cyclosporin A combined with mycophenolate mofetil to prevent graft-versus-host disease. RESULTS AND CONCLUSION:(1)The patients with intestinal acute graft-versus-host disease had diarrhea of varying degrees,most of which were yellow-green,yellow-brown watery stools or mucous stools.53 patients(38.4%)had blood stools,82 patients(57.9%)had skin involvement,18 patients(13.0%)had a secondary intestinal bacterial infection,and 90 patients(65.2%)had cytomegaloviremia.(2)The clinical characteristics of patients(70 cases,50.7%)with grade 1-2 intestinal acute graft-versus-host disease were compared with those(68 cases,49.3%)with grade 3-4 intestinal acute graft-versus-host disease.It was found that the age of grade 3-4 intestinal acute graft-versus-host disease patients was higher than that of grade 1-2 intestinal acute graft-versus-host disease patients(P<0.001),and they were complicated with cytomegaloviremia probably(P=0.035).Diarrhea lasted longer(P=0.00)and the length of hospital stay increased substantially(P<0.001).However,there were no significant differences in recipient gender,pre-transplant disease status,HLA matching,diagnosis,combined skin graft-versus-host disease,and secondary intestinal infection rate in patients of the two groups.(3)These findings conclude that the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation are complex,which affects the prognosis and quality of life of patients seriously and requires early identification and precise treatment.