The 2024 World Conference on Lung Cancer (WCLC) and the European Society for Medical Oncology (ESMO) Annual Meeting, two of the most prestigious events in oncology, have concluded sequentially. As the most authoritative annual gatherings in lung cancer and the entire oncology field, the WCLC and ESMO conferences brought together top oncology experts and scientists from around the world to share, discuss, and publish the latest cutting-edge advancements in oncology. In both conferences, lung cancer immunotherapy remained a hot topic of considerable interest. This article aims to summarize and discuss the important research progress on perioperative immunotherapy for non-small cell lung cancer reported at the two conferences.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Sepsis-acquired weakness (SAW) is a common complication in critically ill patients, yet significant gaps remain in both mechanistic understanding and therapeutic interventions for this condition. SAW not only prolongs the duration of mechanical ventilation and hospitalization but is also closely associated with increased mortality. Even if these SAW patients survive, they often experience long-term physical dysfunction after hospital discharge, leading to diminished quality of life. Emerging evidence suggests that sustained mitochondrial dysfunction may constitute a pivotal pathophysiological basis for the development and progression of SAW, primarily encompassing five key aspects: dysregulated mitochondrial quality control (MtQC), impaired oxidative phosphorylation (OXPHOS), exacerbated oxidative stress, disrupted Ca²⁺; homeostasis, and their mediation of diverse myofiber injuries. This article systematically elucidates the central role of mitochondrial dysfunction in the pathogenesis of SAW. Furthermore, we explore potential therapeutic strategies targeting mitochondrial function, including mitigating mitochondrial oxidative stress, optimizing nutritional support, and supplementing with muscle-derived mesenchymal stem cells. These insights provide a critical theoretical framework for understanding SAW mechanisms and developing clinical interventions, with particular emphasis on the translational value of mitochondrial-targeted therapies in improving outcomes for septic patients.
Humans ; Sepsis/metabolism* ; Mitochondria/metabolism* ; Muscle Weakness/etiology* ; Oxidative Stress ; Oxidative Phosphorylation

Objective:To explore the mechanism of Jianpi Qingchang Decoction in the treatment of UC by integrating network pharmacology, bioinformatics, molecular docking and experimental verification.Methods:The effective components and targets of Jianpi Qingchang Decoction were obtained from TCMSP database, and UC data sets GSE16879, GSE48958 and GSE75214 were obtained from GEO database, and differentially expressed genes were screened; intersection targets were obtained through Venn diagram, and GO function and KEGG pathway enrichment analysis was performed. An intersection target PPI network was constructed using STRING database and topology analysis was performed; hub genes were screened through lasso regression and the expression consistency of core targets in the dataset was verified through logistic regression. A UC mouse model was established and hub genes were validated.Results:A total of 213 drug targets of Jianpi Qingchang Decoction were obtained, and 499 common intersection targets of GSE16879, GSE48958 and GSE75214 were obtained by differential gene expression analysis. Thirty intersection targets of Jianpi Qingchang Decoction and UC were obtained, mainly acting on IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, etc. PPI network topology analysis obtained 7 common intersection targets, including PTGS2, IL-1B, IL-6, MMP9, CXCL8, CCL2 and MMP2. IL-6 and MMP2 were selected as hub genes by lasso regression. Logistics regression analysis showed that IL-6 and MMP2 were risk factors for the disease. Compared with the model group, the expressions of IL-6 and MMP2 mRNA and protein in the colon tissue of the TCM group decreased ( P<0.05), and the morphology of colon tissue was improved compared with the model group. Conclusion:IL-6 and MMP2 are risk factors for UC, the therapeutic effect of Jianpi Qingchang Decoction is to mediate Il-17 signal pathway, TNF signal pathway and AGE-RAGE signal pathway in diabetic complications through the targets of IL-6, and MMP2, thereby treating UC.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

Objective:To preliminarily evaluate the safety and efficacy of shunt-related interventional therapy accompanied with spontaneous portosystemic shunts (SPSS) in patients with hepatic encephalopathy (HE).Methods:Case data on six patients who underwent interventional therapy accompanied by SPSS for HE from January 2017 to March 2021 were collected to evaluate the efficacy and postoperative complications.Results:All six patients underwent SPSS. Four patients had hepatitis B cirrhosis; one had alcoholic cirrhosis; and one had hepatic arterioportal fistula-induced portal hypertension. Child-Pugh liver function scores were C and B in three and three cases, respectively. The SPSS type was gastrorenal shunt in two cases; portal-thoracic-azygos venous in two cases; portal-umbilical-iliac venous in one case; and portal-splenic venous - inferior vena cava in one case. Two of them had previously had a transjugular intrahepatic portosystemic shunt (TIPS), and there were SPSS prior to TIPS. Five cases (5/6) successfully underwent shunt embolization, and one case (1/6) underwent stent implantation for flow restriction (portal-umbilical-iliac vein). The technical success rate was 100%. HE did not recur during hospitalization or the three-month follow-up period. However, one case had a recurrence of HE within a year after surgery and was treated symptomatically, while another experienced gastrointestinal bleeding a year after surgery..Conclusion:SPSS embolization or flow restriction is effective and safe for improving HE patients' symptoms.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Objective:To investigate the clinical and genetic characteristics of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with replication factor C subunit 1 (RFC1) gene mutation to improve the understanding of this disease.Methods:A case of CANVAS diagnosed in the Peking University Third Hospital in January 2021 was reported. Detailed genetic analyses of ataxia were performed with DNA extracted from the peripheral blood of the patient. Studies including pathogenic variants of RFC1 gene causing CANVAS were reviewed and the clinical and genetic characteristics of the disease were summarized.Results:The patient was a 51-year-old female with the prominent manifestation of progressive walking instability. And the clinical data met the diagnostic criteria of CANVAS. The genetic tests excluded other hereditary ataxia mutations and identified the biallelic expansion of the pathogenic variant structure (AAGGG)exp repeat amplification in RFC1 gene. A total of 14 studies on CANVAS with RFC1 gene mutation were reviewed. The overall mutation rate of RFC1 gene in CANVAS was 68%-100%, and it varied in sporadic and familial CANVAS. And the mutation had ethnic differences.Conclusions:Among adult patients with late-onset ataxia, the combination of brain magnetic resonance imaging, electrophysiology tests and vestibular function examination is beneficial to the identification of CANVAS. And the genetic test of RFC1 gene has significant value in the diagnosis of this disease. This patient with CANVAS expands the disease spectrum of ataxia in China, and confirms that RFC1 gene mutation is of great significance in the screening of ataxia disorders in the Chinese population.

Patient satisfaction is one of the core indicators to measure the service quality of medical institutions. To this end, a multi-campus public hospital in Shanghai constructed a management system of patient satisfaction evaluation. Since 2021, its call center has conducted a full coverage satisfaction assessment for discharged patients from its three campuses and collected dissatisfaction information feedback. The hospital organized relevant clinical departments and functional departments to fully communicate with the dissatisfied patients according to the feedback information, followed by a joint rectification. The hospital regularly conducts in-depth analysis of all complaints for timely discovery of common problems in different campuses for continuous improvement. This practice can provide reference for multi-campus hospitals to promote homogeneous management, to improve management efficiency, service quality and patient satisfaction.