Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

OBJECTIVE: To compare clinical effects of external fixation and minimally invasive percutaneous plate osteosynthesis (MIPPO) after external fixation in treating open fractures of tibial shaft. METHODS: From January 2020 to June 2022, 151 patients with open fracture of tibial shaft treated with external fixation stenting were divided into external fixation group and combined group according to different surgical methods. There were 81 patients in external fixation group, including 48 males and 33 females, aged from 21 to 68 years old with an average of (42.58±7.44) years old;according to Gustilo classification, 49 patients with typeⅡ, 32 patients with type ⅢA;the time from injury to treatment ranged from 2.5 to 10 h with an average of (4.25±0.74) h;external fixed stenting was performed. There were 70 patients in combined group, including 42 males and 28 females, aged from 20 to 69 years old with an average of (41.39±7.02) years old;35 patients with type Ⅱ and 35 patients with type ⅢA according to Gustilo classification;the time from injury to treatment ranged from 3 to 9 h with an average of (4.31±0.85) h;MIPPO treatment was performed after external fixed stenting. The time of callus formation, fracture healing and complications were compared between two groups. Rasmussen score and Hospital for Special Surgery (HSS) score were used to evaluate functional recovery of knee joint at 6 months after operation. RESULTS: Both groups were followed up for 6 to 13 months with an average of (10.17±2.33) months. The time of callus formation and fracture healing were (13.98±4.02) d and (70.26±12.15) d in combined group, and (18.56±4.37) d and (79.87±15.41) d in external fixation group, respectively. Combined group was better than external fixation group in the time of callus formation and fracture healing (P<0.05). At six months after operation, Rasmussen and HSS scores in combined group were (26.79±3.11) and (83.36±9.44), which were higher than those in external fixation group (24.51±4.63) and (79.63±8.46) (P<0.05). In external fixation group, there were 2 patients with incision infection, 2 patients with nail tract infection, 1 patient with stent loosening, fracture displacement, delayed union and malunion, and 1 patient with biocompatibility reaction in combined group, with statistical significance between two groups (P<0.05). CONCLUSION MIPPO could accelerate callus formation and fracture healing, improve knee function, improve clinical effects and reduce complications in patients with open tibial shaft fractures after external and external fixation.
Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Bone Plates ; External Fixators ; Fractures, Open/physiopathology* ; Stents ; Young Adult

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

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

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts,often misdiagnosed due to its similarity to many infectious and non-infectious diseases.This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics,including methotrexate,leflunomide,and infliximab,leading to recurrent joint pain,poorly controlled rheumatoid arthritis activity,and persistent elevation of white blood cell counts.Abdominal CT revealed a pelvic mass and right ureteral dilation.Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules,indicating actinomycosis.The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide,hydroxychloroquine sulfate,and tofacitinib,resulting in improved joint symptoms and normalized white blood cell counts.After 2 years of follow-up,the patient remained stable with no recurrence.This case highlights the importance of clinicians being vigilant for infections,particularly chronic,occult infections from rare pathogens,in rheumatoid arthritis patients on potent immunosuppressants and biologics,advocating for early screening and diagnosis.

Objective:To explore the changes in number and immune function of mucosal-associated invariant T (MAIT) cells in peripheral blood of patients with newly diagnosed acute myeloid leukemia (AML),and its correlation with the occurrence and development of AML. Methods:Seventy-five clinical samples of patients with newly diagnosed AML and 48 healthy control samples in our hospital from January 2022 to February 2023 were included. Multiparametric flow cytometry was used to detect the number of MAIT cells,membrane surface markers,effector phenotypes and functional indicators in the samples. Results:Compared with healthy controls,the percentage of MAIT cells in CD3+T cells in peripheral blood of newly diagnosed AML patients was significantly reduced (P<0.001). The percentage of MAIT cells in all CD3+T cells in bone marrow of AML patients was similar to that in peripheral blood (P>0.05). Most of MAIT cells in peripheral blood of AML patients were effector memory T cells. Compared with healthy controls,the proportion of effector memory MAIT cells decreased (P<0.05),while the proportion of terminally differentiated effector memory MAIT cells and PD-1+MAIT cells increased significantly (both P<0.05). AML patients' peripheral blood MAIT cells expressed significantly higher levels of granzyme B and perforin than healthy controls (both P<0.05),and secreted significantly lower levels of cytokines such as gamma interferon and tumor necrosis factor α than healthy controls (both P<0.001). Conclusion:Compared with healthy controls,the proportion of MAIT cells in AML patients is reduced and the expression of functional markers is abnormal,suggesting that their function is impaired and may be involved in the occurrence and development of AML.

The incidence and mortality rate of heart failure (HF) are increasing annually, resulting in a huge medical and economic burden worldwide. B-type natriuretic peptide (BNP) is the gold standard biomarker of HF recommended by national and international guidelines for the diagnosis and prognosis evaluation of HF. Recent studies suggest that BNP can be truncated in multiple forms by different enzymes rather than complete fragments in circulation, which can be contributing to the diagnosis and classification of HF. The immunoassay mostly used in clinics are unable to distinguish different truncated BNP forms due to cross-reactivity of antibody, while mass spectrometry is more accurate because it can easily distinguish through their mass-to-charge ratios. With the maturation of ambient ionization mass spectrometry and ion mobility mass spectrometry, it can help to simplify sample pre-treatment and improve the separation efficiency, in order to explore the clinical value of the heterogeneity of BNP truncated forms.

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.