ObjectiveTo observe the protective effect of Erchentang （ECT） on SiO₂-induced lung injury in rats and to explore its underlying mechanism. MethodsA rat model of lung injury was established by a single intratracheal instillation of 50 mg·mL^-1 SiO₂ suspension. Thirty male Sprague-Dawley （SD） rats were randomly assigned to five groups： control， model， low and high-dose （4.5 g·kg^-1·d^-1 and 9 g·kg^-1·d^-1， respectively） ECT， and dexamethasone （0.2 mg·kg^-1·d^-1）. All the groups were treated for 4 consecutive weeks. Histopathological alterations in the lung tissue were examined by hematoxylin and eosin （HE） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue were measured through biochemical assays. The expression of key molecules in the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway was determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunofluorescence assay. The primary active components of ECT were identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and their binding affinity to Nrf2/HO-1 was assessed by molecular docking. Untargeted metabolomics of the lung tissue was performed based on UPLC-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and correlation analysis was performed to identify differential metabolites and parameters closely associated with the Nrf2/HO-1 pathway. ResultsCompared with the control group， the model group exhibited a reduction in body weight gain， an increase in lung index， increased MDA content， weakened SOD and GSH-Px activities in the lung tissue， down-regulated mRNA and protein levels of Nrf2 and protein levels of HO-1 and GPX4， and an up-regulated protein level of Keap1 （P<0.05， P<0.01）. Treatment with ECT attenuated the SiO₂-induced decline in body weight （P<0.05）， alleviated inflammatory cell infiltration and silicotic nodule formation in alveoli， and reduced the MDA content and enhanced the SOD and GSH-Px activities in the lung tissue （P<0.05， P<0.01）. UPLC-MS/MS and molecular docking revealed that core components of ECT， such as hesperidin and glycyrrhizic acid， displayed strong binding affinity to Nrf2/HO-1. Molecular biological experiments demonstrated that ECT promoted nuclear translocation of Nrf2， up-regulated the mRNA and protein levels of HO-1 and GPX4， and down-regulated Keap1 expression （P<0.05， P<0.01）. Metabolomic analysis indicated that ECT reversed the SiO₂-induced aberrant expression of metabolites， including linoleic acid and glutamine （P<0.05， P<0.01）. Correlation analysis showed that Nrf2 and HO-1 were positively correlated with SOD and GSH-Px （P<0.05， P<0.01）， but negatively correlated with glutamine and serine （P<0.05， P<0.01）. ConclusionECT may activate the Nrf2/HO-1 pathway through its core active components， thereby regulating oxidative stress and metabolic disorders to ameliorate SiO₂-induced lung injury in rats. This study provides experimental evidence for ECT in the prevention and treatment of occupational lung injury.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Most cases are caused by non-small-cell lung cancer (NSCLC). Over the past three decades, the treatment landscape of NSCLC has been profoundly reshaped by the discovery of epidermal growth factor receptor (EGFR) mutations and the subsequent development of EGFR-targeted therapies. This review provides a comprehensive overview of the evolution of four generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs): first-generation reversible inhibitors such as gefitinib and erlotinib; second- and third-generation irreversible inhibitors, including afatinib, dacomitinib, and osimertinib; and emerging fourth-generation agents, such as amivantamab. Each generation has contributed to efficacy improvement, central nervous system penetration, and resistance management. Despite remarkable advances in development of EGFR-TKIs, acquired resistance and tumor heterogeneity remain major challenges. Bioinformatic analyses using The Cancer Genome Atlas (TCGA) datasets highlight the high mutation frequency and clinical significance of EGFR alterations, underscoring their pivotal role in tumor progression and prognosis. Future studies should explore combination therapies, antibody–drug conjugates, and next-generation allosteric inhibitors as promising strategies to overcome resistance. The evolution of EGFR-targeted therapy exemplifies the progress of precision oncology and serves as a basis for designing new paradigms in the management of lung cancer.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

The paper introduces the diagnostic and therapeutic ideas and clinical experience of Professor LIU Zhibin in treatment with acupuncture for Parkinson's disease with mild cognitive impairment. Professor LIU believes that the basic pathogenesis of Parkinson's disease with mild cognitive impairment refers to the deficiency of liver and kidney, and the loss of mind control. Therefore, the treatment focuses on nourishing the liver and kidney, regulating the governor vessel, opening the brain orifice, and regulating the mind. The point prescription is composed of Tongdu Tiaoshen zhen (the points for promoting the circulating of the governor vessel and regulating the mind, i.e. four-mind needles [Extra], Shenting [GV24], bilateral Benshen [GB13] and Fengfu [GV16]), xiusanzhen (three-olfaction needles, including bilateral Yingxiang [LI20] and Yintang [GV24⁺]) and zhichan bazhen (eight anti-tremble needles, i.e. Baihui [GV20], Lianquan [CV23], and Hegu [LI4], Waiguan [TE5], Taichong [LR3], Zusanli [ST36], Sanyinjiao [SP6] and Taixi [KI3] on the affected side). Besides, the prescription is modified according to the syndrome, and the special technique of bone-touching needling is combined to enhance the therapeutic effect.
Humans ; Acupuncture Therapy ; Parkinson Disease/psychology* ; Cognitive Dysfunction/complications* ; Male ; Acupuncture Points ; Female ; Aged ; Middle Aged

This paper introduces Professor LIU Zhibin 's clinical experience in the treatment of subjective tinnitus with acupuncture based on the "kidney-bone-brain" axis. Professor LIU proposes that the disease is most closely related to the kidney and brain. The lesion is located in the brain, and the pathogenesis is kidney essence deficiency, marrow sea loss, and ear orifice dystrophy. The "kidney-bone-brain" shows close correlation in physiological function, pathological changes and treatment. According to the "kidney-bone-brain" axis, Professor LIU proposes that the treatment of subjective tinnitus should be tonifying kidney qi, tonifying essence and filling marrow, and the principle of local acupoint selection, touching bone acupuncture, matching distal acupoints and proximal acupoints, tonifying kidney and benefiting brain should be adopted. The acupoints of Tinggong (SI19) and Yifeng (TE17) are selected to be treated with touching bone acupuncture, combined with Taixi (KI3), Shenshu (BL23), Baihui (GV20) and Shenting (GV24), so as to achieve common benefit of kidney, bone and brain, and multi-angle treatment.
Humans ; Acupuncture Therapy/history* ; Tinnitus/physiopathology* ; Acupuncture Points ; Kidney/physiopathology* ; Brain/physiopathology* ; Bone and Bones/physiopathology* ; Female ; Male ; Adult ; Middle Aged

Objective To compare the efficacies of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in the treatment of post-chronic aplastic anemia(CAA)myelodysplastic syndrome(MDS)and primary MDS.Methods A retrospective analysis was conducted on 32 patients who received allo-HSCT treatment in Department of Hematology,North China University of Science and Technology Affiliated Hospital between Feb.2012 and Feb.2022,including 12 patients with post-CAA MDS and 20 patients with primary MDS.The overall survival rate,cumulative incidence of relapse(CIR)rate,non-relapse mortality(NRM)rate,and event-free survival rate were compared between the 2 groups.Results The median follow-up time for CAA to progress to MDS was 120(72-180)months.All the patients were followed up for 36(3-79)months after allo-HSCT.The 3-year overall survival rate of the post-CAA MDS group was significantly higher than that of the primary MDS group(83.8%vs 45.0%,P=0.035).The 3-year CIR of the post-CAA MDS group was significantly lower than that of the primary MDS group(16.7%vs 55.0%,P=0.021).There was no significant difference in the event-free survival rates or NRM rates between the 2 groups(both P＞0.05).Conclusion The post-CAA MDS patients have better survival after allo-HSCT than the primary MDS patients.Early allo-HSCT treatment may improve the prognosis.

Objective:To establish a quantitative diagnostic standard for Crohn's disease with dampness syndrome based on clinical data using a disease syndrome combination model and conduct bidirectional validation.Methods:256 patients with Crohn's disease from the Department of Spleen and Stomach Diseases at Guangdong Provincial Hospital of Chinese Medicine, the Department of Gastroenterology at the Sixth Affiliated Hospital of Sun Yat-sen University, and the Outpatient Department of Guangdong Provincial Hospital of Chinese Medicine from October 2021 to January 2022 were selected as the observation objects. They were divided into an operation group of 205 patients and a verification group of 51 patients in an 8:2 ratio using a random number table method. The frequency advantage method, χ2 test, and binary logistic regression analysis were used to screen for relevant standard factors. The conditional probability method was used to assign scores to relevant items, and the maximum likelihood method was used to determine the quantitative diagnostic threshold. A quantitative diagnostic standard for Crohn's disease with dampness syndrome based on disease syndrome combination was established, and it was retrospectively analyzed and prospectively verified. Results:On the basis of the 20 candidate quantitative diagnostic criteria items for Crohn's disease dampness syndrome, binary logistic regression analysis was performed to calculate the OR values between each item. The quantitative diagnostic criteria for Crohn's disease with dampness syndrome included tongue coating greasiness (7 points), body heaviness (13 points), waist and knee soreness (8 points), head weight (9 points), bland mouth (6 points), anal heaviness (8 points), uncomfortable bowel movements (8 points), and sticky stools (7 points), with a quantitative diagnostic threshold of 11. Conclusion:The scoring of relevant items in the quantitative diagnostic criteria for Crohn's disease with dampness syndrome is reasonable and has good diagnostic value, which can provide reference for further quantitative research on Crohn's disease syndromes.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.