ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Objective To explore the diagnostic value of endoscopic grading of gastric intestinal metaplasia (EGGIM) score under acetic acid-enhanced narrow band imaging (AA-NBI) observation mode for gastric intestinal metaplasia (GIM). Methods A total of 120 patients who underwent gastroscopy at Jinshan Hospital of Fudan University from February 2022 to February 2023 were selected. All patients underwent both white light and AA-NBI endoscopy, with photographic records of intestinal metaplasia in five areas: greater curvature of antrum, lesser curvature of antrum, greater curvature of corpus, lesser curvature of corpus and incisura. EGGIM score was performed: 0 for no intestinal metaplasia, 1 point for focal intestinal metaplasia (GIM area ratio≤30%), 2 points for extensive intestinal metaplasia (GIM area ratio＞30%), with a total score of 10 points. Targeted biopsies were performed on suspicious GIM lesions found during endoscopy. If no suspicious GIM lesions were observed, random biopsies were performed according to the updated Sydney system. The pathological histological examination results were staged based on the operative link on gastric intestinal metaplasia assessment (OLGIM) system. The diagnostic value of EGGIM score for OLGIM stage Ⅲ-Ⅳ patients was evaluated using receiver operating characteristic (ROC) curves. Results The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of AA-NBI in detecting GIM were 96.3%, 91.6%, 94.5%, 95.0%, and 93.6%, respectively. The area under the ROC curve for EGGIM diagnosing OLGIM stage Ⅲ-Ⅳ was 0.952 (95%CI 0.914-0.990). The optimal cut-off value for EGGIM was 5 points, with a sensitivity of 96.7% (95%CI 87.6%-99.4%) and specificity of 88.1% (95%CI 76.5%-94.7%). Conclusions EGGIM score (≥5 points) under AA-NBI mode has good diagnostic capability for patients with OLGIM stage Ⅲ-Ⅳ.

Objective To analyze the external radiation dose rate and radiation protection measures during treatment of a patient with hepatocellular carcinoma (HCC) who underwent ⁹⁰Y selective internal radiotherapy (⁹⁰Y-SIRT). Methods A male HCC patient who received ⁹⁰Y-SIRT with an activity of 4.65×10⁹ Bq was selected as the research subject using retrospective analysis. External radiation dose rate meters were used to detect ambient dose equivalent rates around the radiation worker, the HCC patient, and the workplace during treatment. Surface contamination meters were used to detect surface contamination levels of the radiation worker and the workplace. Results The ambient dose equivalent rate around the interventional radiology staff during treatment ranged from 3.7 to 39.0 μSv/h. The patient's ambient dose equivalent rate of surgical site at distances of 30, 100, and 200 cm ranged from 45.0 to 5.6, 4.4 to 0.4, and 0.4 to 0.1 μSv/h respectively without protection, and 14.0 to 3.4, 3.2 to 0.3, and 0.4 to 0.1 μSv/h respectively when the surgical site was covered with a 1.0 mmPb lead rubber drape after 0.0 to 161.0 hours of the surgery. In the nuclear medicine department, ambient dose equivalent rate of the workplace ranged from 0.4 to 740.0 μSv/h. The ambient dose equivalent rate around all monitoring points in the digital subtraction angiography operating room accounted at 0.1 μSv/h, and the observation ward ranged from 0.1 to 0.2 μSv/h. The β surface contamination levels of the radiation worker and workplace were below the minimum detection limit (0.16 Bq/cm²). Conclusion Radiation doses for both HCC patients and radiation worker remained within acceptable limits when appropriate protective equipment was used. A well-designed workplace layout is essential to ensure effective implementation of radiation protection.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

Objective To investigate the effects of crocetin on radiosensitivity of lung adenocarcinoma and its potential mechanisms using a nude mouse xenograft model established with A549 lung adenocarcinoma cells. Methods Forty mice bearing lung adenocarcinoma were randomly divided into four groups: control group, crocetin group, radiotherapy group, and crocetin combined with radiotherapy group, and received the corresponding interventions. After 14 days of treatment, all mice were sacrificed and tumor tissues were excised. Tumor weight was measured in each group and the tumor inhibition rate was calculated. Apoptosis of tumor cells was analyzed by flow cytometry. Immunohistochemistry and RT-qPCR were used to detect and compare the expression of genes encoding hypoxia-inducible factor (HIF-1α) and B-cell lymphoma-2 (BCL-2). Results The mean tumor weight of mice in the crocetin combined with radiotherapy group was significantly lower than that in the radiotherapy group (P < 0.05), and the tumor inhibition rate of the crocetin combined with radiotherapy group was 34.07%. The mean tumor cell apoptosis rate in the crocetin combined with radiotherapy group was significantly higher than that in the radiotherapy group (P < 0.05). HIF-1α expression was significantly lower in the crocetin combined with radiotherapy group than in the radiotherapy group (P = 0.001). Although BCL-2 expression in the crocetin combined with radiotherapy group was lower than that in the radiotherapy group, the difference was not statistically significant (P = 0.894). The expression levels of mRNAs of genes encoding HIF-1α and BCL-2 in the crocetin combined with radiotherapy group were significantly lower than those in the radiotherapy group (P < 0.05). Conclusion Crocetin in combination with radiotherapy significantly enhanced the inhibitory effect of radiotherapy on tumor growth in mice bearing lung adenocarcinoma and increased the tumor inhibition rate. The mechanisms may involve the alleviation of radiotherapy-induced overexpression of HIF-1α, thereby improving hypoxic conditions in tumor tissues, as well as suppression of the anti-apoptotic gene BCL-2 to enhance radiotherapy-induced apoptosis of lung adenocarcinoma cells.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

ObjectiveTo investigate the differences in efficacy and endogenous metabolic mechanisms of Anmeidan with combined use of raw and fried Ziziphi Spinosae Semen and its disassembled prescriptions in treating anxiety and cognitive impairment in insomnia rats. MethodsSixty rats were randomly divided into six groups （n=10 per group）： blank group， model group， suvorexant group （30 mg·kg^-1）， Anmeidan group （9.09 g·kg^-1）， Anmeidan with absence of raw Ziziphi Spinosae Semen group （7.38 g·kg^-1）， and Anmeidan with absence of fried Ziziphi Spinosae Semen group （7.38 g·kg^-1）. An insomnia model was constructed by intraperitoneal injection of para-chlorophenylalanine （PCPA）， followed by gavage administration of Anmeidan or its disassembled prescriptions. Anxiety levels were assessed using the open field test， while cognitive ability was evaluated via the novel object recognition test. The pathological morphology of hippocampal neurons was examined using electron microscopy. Serum samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for principal component analysis， metabolic profiling， identification of differential metabolites， and metabolic pathway analysis. ResultsCompared with the blank group， the model group exhibited significantly increased exercise mileage， exercise time， and the ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones exhibited a marked increase （P<0.05， P<0.01）， while the novel object recognition index significantly decreased （P<0.05）. Compared with the model group， the Anmeidan and suvorexant groups showed significantly reduced exercise mileage and exercise time （P<0.01）. The ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones decreased （P<0.05）， and a significant increase in the novel object recognition index （P<0.01）. However， the disassembled prescription groups showed no significant improvement in open field test and novel object recognition test indices. Electron microscopy revealed that the Anmeidan group improved the pathological morphology of hippocampal neurons in insomnia rats. Metabolomics analysis identified 10 potential differential metabolites associated with Anmeidan's therapeutic effects， involving metabolic pathways related to phenylalanine and tryptophan biosynthesis and metabolism， as well as the serotonergic pathway. ConclusionThe combined use of raw and fried Ziziphi Spinosae Semen in Anmeidan is more effective than its disassembled prescriptions in alleviating anxiety and cognitive impairment in PCPA-induced insomnia rats. The underlying mechanism may be associated with metabolic pathways related to phenylalanine， tryptophan， and serotonin.