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.

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective To investigate the inhibitory effect of farrerol on inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt and its molecular mechanism based on the Janus kinase 2(JAK2)/Transcription activator 3(STAT3)pathway.Methods A total of fifty C57BL/6J mice were randomly divided into normal group(normal feeding),model group(high salt diet),experimental-L group(high salt diet+oral administration of 12.5 mg·kg-1·d-1 farrerol),experimental-M group(high salt diet+oral administration of 25 mg·kg-1·d-1 farrerol)and experimental-H group(high salt diet+oral administration of 50 mg·kg-1·d-1 farrerol).The model was prepared for 12 weeks.The contractile response of the cerebral basilar artery of mice in each group to vasoconstrictor was recorded with myographs.Enzyme linked immunosorbent assay(ELISA)were used to detect the levels of inflammatory factor.The protein expression levels of JAK2/STAT3 pathway related proteins were detected by Western blot.Results In the normal group,model group,experimental-L group,experimental-M group,experimental-H group,the contraction effects of the cerebral basilar artery to 60 mmol·L-1 potassium chloride(KCl)were(2.19±0.13),(2.66±0.11),(2.52±0.09),(2.41±0.08)and(2.25±0.10)mN;the contraction effects to 10-5 mol·L-1 vasopressiu(AVP)were(1.98±0.09),(2.46±0.08),(2.33±0.12),(2.11±0.10)and(2.05±0.06)mN;the contraction effects to 2.5 mmol·L-1 calcium chloride(CaCl2)were(1.77±0.08),(2.09±0.09),(2.03±0.08),(1.94±0.05)and(1.86±0.06)mN;in the serum,the levels of interleukin(IL)-1β were(10.10±3.21),(47.28±4.78),(40.16±3.98),(35.87±4.12)and(20.32±3.17)pg·mL-1;the levels of tumor necrosis factor-α(TNF-α)were(60.26±5.43),(134.32±4.15),(110.65±3.56),(90.79±5.25)and(81.54±6.23)pg·mL-1;the levels of chemokine ligand 3(CCL3)were(68.93±4.16),(146.37±5.73),(128.29±4.38),(100.25±6.82)and(84.16±3.89)pg·mL-1;the protein expression levels of JAK2 were 0.52±0.05,1.28±0.07,1.11±0.06,0.88±0.09 and 0.75±0.04;the protein expression levels of STAT3 were 0.58±0.07,1.93±0.10,1.62±0.04,1.34±0.06 and 0.88±0.09,respectively.The above indicators in the model group were significantly higher than the normal group(all P＜0.01);compared to the model group,the above indicators in the experimental-M and-H groups were significantly reduced(P＜0.05,P＜0.01).Conclusion Farrerol maybe improve the inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt by downregulating JAK2/STAT3 pathway.

Objective:To investigate the clinical outcome of endovascular treatment vs. drug treatment in patients with symptomatic non-acute long-segment occlusion of the internal carotid artery. Methods:Based on prospective cohort registration research data, patients with symptomatic non-acute long-segment occlusion of internal carotid artery were retrospectively included. They were divided into a drug treatment group and an endovascular treatment group according to the actual treatment received. The latter was further divided into a successful recanalization group and an unsuccessful recanalization group. The endpoint events included ipsilateral ischemic stroke, any stroke, and all-cause death. Multivariate logistic regression analysis was used to compare the endpoint events between groups during the perioprocedural period (within 30 days), and multivariate Cox proportional hazards model was use to compare the endpoint events between the groups during the long-term follow-up. Results:A total of 684 patients were included, of which 570 (83.33%) were male, median aged 63 years (interquartile range, 56-70 years). Three hundred and fifty-three patients (51.6%) received drug treatment; 331 (48.4%) received endovascular treatment, of which 161 (48.6%) had successful recanalization. The median follow-up time was 1 223 days (interquartile range, 646.5-2 082 days), with 109 patients (15.9%) experiencing stroke recurrence events (including 87 ipsilateral ischemic stroke) and 78 (11.4%) experiencing all-cause mortality. The risk of any stroke during the perioprocedural period in the successful recanalization group was significantly higher than that in the drug treatment group (odds ratio 3.679, 95% confidence interval 1.038-13.036; P=0.044), but the risk of ipsilateral ischemic stroke recurrence (risk ratio 0.347, 95% confidence interval 0.152-0.791; P=0.012) and all-cause mortality (risk ratio 0.239, 95% confidence interval 0.093-0.618; P=0.003) during the long-term follow-up were significantly lower than those in the drug treatment group. Conclusions:In patients with symptomatic non-acute long-segment occlusion of the internal carotid artery, endovascular treatment can increase the risk of stroke recurrence within 30 days, but successful recanalization can reduce the risks of long-term ipsilateral ischemic stroke recurrence and all-cause mortality.

Purpose::The reconstruction of Allen's type IV fingertip amputation is a clinical challenge. Our team designed bilateral unequal-sized hallux osteo-onychocutaneous free flaps for the long-term reconstruction of Allen's type IV fingertip amputation and conducted a retrospective study with a 5-year follow-up aims to evaluate the effects of this technique.Methods::A retrospective analysis with a 5-year follow-up including 13 patients with Allen's type IV fingertip amputation who were admitted to our hospital from January 2010 to January 2017 was conducted. The patients were treated with bilateral unequal-sized hallux osteo-onychocutaneous free flaps. The operation time, intraoperative blood loss, and complications were recorded, and the survival rate of the transplanted flaps was calculated. During the 5-year follow-up after operation, the nail growth time was recorded and the finger appearance was observed. At the last follow-up appointment, the length, width, and girth of the reconstructed fingertip and contralateral normal fingertip, range of motion of the reconstructed fingertip and contralateral normal fingertip, Semmes-Weinstein test (for the evaluation of tactile sensation), and two-point discrimination testing results were recorded. SPSS 22.0 software was used for the statistical analysis and the data are presented as mean ± SD.Results::The mean operation time was (5.62 ± 0.51) h, the mean intraoperative blood loss was (34.15 ± 3.13) mL, and the survival rate of the transplanted flaps was 100%. During the 5-year follow-up, the average nail growth time was (10.14 ± 1.98) months and the average bone union time was (3.78 ± 0.91) months. The length, width, and girth of the reconstructed fingertip were (31.52 ± 3.73) mm, (17.82 ± 1.74) mm, and (59.75 ± 3.04) mm, respectively, which did not differ from those of the contralateral normal fingertip. The range of motion of the reconstructed fingertip was (12.15 ± 2.79) degrees which is different from that of the contralateral normal fingertip. The average tactile sensation evaluated via the Semmes-Weinstein test and the average two-point discrimination test of the reconstructed fingertip were (0.39 ± 0.17) g and (7.46 ± 1.14) mm, respectively, which were not different from those of the contralateral normal fingertip. The average Maryland score of feet in the donor area was 87.66 ± 7.39, which was satisfactory.Conclusion::Bilateral unequal-sized hallux osteo-onychocutaneous free flaps are an effective method to reconstruct Allen's type IV fingertip amputations with a satisfactory appearance and good sensory function.

Objective:To investigate the risk factors of decreased medication compliance of β-receptor blocker in patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:A total of 160 CHD patients undergoing PCI from January 2020 to July 2021 in our hospital were selected.According to post-operative Morisky medication adherence scale(MMAS-8)score,they were divided into high compliance group(n=100,≥6 points)and low compliance group(n=60,＜6 points).Univariate and multivariate Logistic regression analysis were conducted to analyze the influencing factors of decreased medication compliance of β-receptor blocker in CHD patients after PCI.Results:The mean MMAS-8 score of 160 patients was(5.81±0.12)points.Com-pared with high compliance group,there were significant reductions in percentages of age＜60 years(74.00％vs.36.67％),high school or higher education(68.00％vs.40.00％),stent implanted duration＜2 years(54.00％vs.28.33％),family APGAR index score[(5.12±1.60)points vs.(4.52±2.10)points],proportion of APGAR score≥7 points(68.00％vs.33.33％),and significant rise in percentages of family income＜3000 RMB(34.00％vs.61.67％),self-paying(36.00％vs.60.00％),diabetes(47.00％vs.66.67％)and hypertension(42.00％vs.65.00％)in low compliance group,P＜0.05 or＜0.01.Multivariate Logistic regression analysis indicated that junior high school education,age ≥60 years,family income＜3000 RMB,self-paying,stent implanted duration≥2 years,hypertension and diabetes were independent risk factors for decreased medication compliance of β-re-ceptor blocker in CHD patients after PCI(OR=8.445～97725.056,P＜0.05 or＜0.01),while APGAR score ≥7 points was its independent protective factor(OR=0.005,P=0.001).Conclusion:The influencing factors for de-creased medication compliance of β-receptor blocker in CHD patients after PCI include age,stent implanted dura-tion,education level etc.It is necessary to focus on monitoring the medication of patients with risk factors and per-form intervention,which is helpful to improve medication compliance.

OBJECTIVE: To investigate the effects of different manners of heat exposure on thoracic aorta injury in spontaneously hypertensive rats (SHRs) and explore the underlying mechanism. METHODS: Normal 6 to 7-week-old male SHRs were randomized into control group (cage at room temperature), intermittent heat exposure group (SHR-8 group, exposed to 32 ℃ for 8 h daily for 7 days) and SHR-24 group (with continuous exposure to 32 ℃ for 7 days). After the treatments, the pathologies of the thoracic aorta of the rats were observed with HE staining, and the expressions of Beclin1, LC3B and p62 were detected with Western blotting and immunofluorescence assay; TUNEL staining was used to observe cell apoptosis in the thoracic aorta, and the expressions of caspase-3, Bax, and Bcl-2 were detected using Western blotting. The effects of intraperitoneal injections of 3-MA (an autophagy agonist), rapamycin (an autophagy inhibitor) or compound C 30 min before intermittent heat exposure on the expressions of proteins associated with autophagy, apoptosis and the AMPK/mTOR/ULK1 pathway in the aorta were examined with immunohistochemistry. RESULTS: In SHR-8 group, the rats showed incomplete aortic intima with disordered cell distribution and significantly increased expressions of Beclin1, LC3II/LC3I and Bax, lowered expressions of p62 and Bcl-2, and increased apoptotic cells in the thoracic aorta (P < 0.05). Pretreatment with 3-MA obviously inhibited the expressions of autophagy- and apoptosis-related proteins, whereas rapamycin promoted their expressions. Compared with the control group, the rats in SHR-8 group had significantly down-regulated p-mTOR and up-regulated p-AMPK and p-ULK1 expression of in the aorta; Treatment with compound C obviously lowered the expressions of p-AMPK and p-ULK1 and those of LC3B and Beclin1 as well. CONCLUSION In SHRs, intermittent heat exposure causes significant pathologies and promotes autophagy and apoptosis in the thoracic aorta possibly by activating the AMPK/mTOR/ULK1 pathway.
Rats ; Male ; Animals ; Rats, Inbred SHR ; AMP-Activated Protein Kinases/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Aorta, Thoracic ; Beclin-1 ; Hot Temperature ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis ; Aortic Diseases ; Autophagy ; Autophagy-Related Protein-1 Homolog/metabolism*