ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Occupational noise-induced hearing loss (NIHL) is an irreversible sensorineural hearing loss that severely endangers workers’ health, making early screening crucial. This article reviewed the research progress on early screening methods for occupational NIHL, introduced the testing mechanisms of three core screening methods—tympanometry, otoacoustic emissions, and extended high-frequency audiometry —and summarized their clinical application advantages and limitations. It is proposed that multimodal combined detection (e.g., the combination of tympanometry, otoacoustic emissions, and extended high-frequency audiometry) can significantly improve the accuracy and comprehensiveness of early screening. Meanwhile, future studies with prospective cohort design are encouraged to verify the long-term monitoring value of each method and to strengthen the joint development of screening technologies with cutting-edge approaches such as machine learning, in order to further improve screening efficiency and provide stronger protection for workers’ hearing health.

Objective: To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata (Willd.) Ohwi root (P. lobata, Ge Gen) and Hovenia dulcis Thunb. (H. dulcis, Zhi Ju Zi) against ethanol-induced liver damage in vitro, using a human hepatoma cell line G2 (HepG2) cell model. Methods: HepG2 cells were cultured in medium containing 4% ethanol to establish a model of alcoholic liver damage. The cells were then treated with the combined extract obtained via cryogenic extraction. Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers, antioxidant enzymes, and inflammatory cytokines. In addition, activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was examined to elucidate the mechanisms underlying the effects of the extract. Results: Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells; promoted the elevated expression of superoxide dismutase, catalase, and glutathione, indicating enhanced antioxidant defenses; and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals. In addition, by activating the PI3K/AKT pathway, treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets, subsequently inhibiting apoptosis. Moreover. inflammatory responses were mitigated, as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6, and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase, thereby indicating hepatoprotective effects. Conclusion The combined P. lobata root and H. dulcis extract was established to have notable antioxidative and anti-inflammatory properties, effectively alleviating ethanol-induced liver damage in vitro. These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.

Objective To investigate differential patterns of oxygenated hemoglobin concentration in prefron-tal cortical regions between major depressive disorder patients with or without psychotic symptoms during verbal flu-ency task(VFT)performance using functional near-infrared spectroscopy(fNIRS).Methods A total of 108 pa-tients with major depression who were hospitalized in the psychiatric department of the hospital from July 2023 to April 2024 were selected as the study objects.They were divided into two groups(n=60)with or without psychotic symptoms(n=48).fNIRS devices were used to measure and compare the changes in the relative concentration of cerebral hemoglobin in 52 brain channels between the two groups during VFT.Re-sults Compared with the unaccompanied group,the relative concentration of cerebral oxygenated hemoglobin in channel 13 was higher(0.003±0.001 vs.0.002±0.001),and the relative concentration of cerebral oxygen-ated hemoglobin in channel 33 was lower(0.003±0.001 vs.0.007±0.002),the difference was statistically significant(P＜0.05).There was no significant difference in the relative concentration of oxygenated hemo-globin in other brain areas between the two groups(P＞0.05).Conclusion There are abnormal oxygen activ-ity in brain functional areas associated with psychotic symptoms,and fNIRS technique is helpful for early as-sessment of cerebral aerobic function in depressed patients with psychotic symptoms.

Atopic dermatitis（AD）is a chronic，recurrent inflammatory skin disease.The pathogenesis of AD is complicated，involving many factors such as genetic，immune，and skin barrier.Previous studies have attributed skin barrier dysfunction to the changes in skin microbiota caused by immune disorders.In recent years，researchers have found that abnormal immune regulation related to the gut microbiota may be an important factor that leads to the development of AD.Gut microbiota dysbiosis and metabolomic disorders are of great significance to explore the pathogenesis of AD.The treatment of AD is currently focused on topical anti-inflammatory drugs，but the long-term efficacy is poor.Therefore，the treatment of fecal microbiota transplantation based on correcting gut microbiota dysbiosis came into being.This article summarized the current research status of gut microbiota dysbiosis in the occurrence and progression of AD，and the application progress and efficacy of fecal microbiota transplantation in children with AD，providing reference for the etiological analysis and clinical intervention of AD.

Background and objective Invasive mucinous adenocarcinoma(IMA)was a rare and specific type of lung adenocarcinoma,which was often characterized by fewer lymphatic metastases.Therefore,it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis(TNM)staging.So,this study aimed to develop Nomo-grams to predict outcomes of patients with pathologic N0 in resected IMA.Methods According to the inclusion criteria and exclusion criteria,IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University(training cohort,n=78)and Ningbo No.2 Hospital(validation cohort,n=66)were reviewed between July 2012 and May 2017.The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established,and the performances of models were evaluated.Finally,the validation cohort data was put in for external validation.Results Univariate analysis showed that pneumonic type,larger tumor size,mixed mucinous/non-mucinous component,and higher overall stage were significant influence factors of 5-year progression-free survival(PFS)and overall survival(OS).Multivariate analysis further indicated that type of imaging,tumor size,mucinous component were the independent prognostic factors for poor 5-year PFS and OS.Moreover,the 5-year PFS and OS rates were 62.82％and 75.64％,respectively.In subgroups,the sur-vival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients,respectively.The C-index of Nomograms with 5-year PFS and OS were 0.815(95％CI:0.741-0.889)and 0.767(95％CI:0.669-0.865).The calibration curve and decision curve analysis(DCA)of both models showed good predictive performances in both cohorts.Conclusion The Nomograms based on clinicopathological characteristics in a certain extent,can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.

Objective To explore the potential value of serum lipoxin A4 (LXA4) in monitoring bacterial load and anti-tuberculosis treatment progression in patients with pulmonary tuberculosis (PTB). Methods From January 2021 to January 2022, forty patients with active PTB, who were admitted to Shaanxi Provincial Tuberculosis Prevention and Control Hospital, were selected as the active PTB group, 38 patients with latent tuberculosis infection (LTBI) were selected as the LTBI group, and 28 healthy volunteers who underwent physical examination in our hospital during the same period were included as the healthy control group. The active PTB patients received a 2-month standard anti-tuberculosis chemotherapy, while the other two groups were untreated. Fasting venous blood was drawn from the three groups at enrollment (baseline), after 2 months of treatment, and upon the completion of 6 months of treatment in the active PTB group to measure serum LXA4 levels using enzyme-linked immunosorbent assay (ELISA). The relationship between serum LXA4 level and clinical manifestations, bacterial load, chest imaging manifestations, and treatment progress was analyzed. Results At baseline, serum LXA4 levels in the active PTB group, LTBI group, and healthy control group were [397.72 (210.68, 573.00)], [178.18 (108.17, 271.87)], and [131.06 (76.24, 166.04)] pg/mL, respectively. The levels in the active PTB and LTBI groups were significantly higher than those in the healthy control group, with statistical significance (P<0.01). According to the grading of acid-fast bacilli (AFB) sputum smears at diagnosis, baseline serum LXA4 level increased in the active PTB group with AFB sputum smear grade (P<0.001), and there was a positive correlation between serum LXA4 level and sputum smear grade (rs=0.209, P=0.003). After 6 months of treatment, the serum LXA4 level in the active PTB group was lower than the baseline value (P=0.002). The serum LXA4 level can predict treatment progress, with a baseline sensitivity of 55.0% (22/40), and after 6 months of treatment, 8 patients (20.0%) still showed positive serum LXA4 levels. Conclusions Serum LXA4 may be a useful biomarker for monitoring the progression of PTB treatment.

The report of the 20th National Congress of the Communist Party of China has made a major deployment to promote the expansion of high-quality medical resources and balanced regional layout, and the construction of national regional medical centers is an important measure to implement the landing. By analyzing the " three co-construction" mode of the National Children′s Regional Medical Center of Henan Children′s Hospital (Beijing Children′s Hospital Zhengzhou Hospital), this paper systematically introduced the internal and external decision-making, management and operation of the regional medical center from four aspects: management, talent, discipline and system. The practice and effectiveness in talent introduction and training, salary distribution, two-way communication, assessment and incentive, discipline construction, technology application, sharing and evaluation of scientific and technological innovation, institutional linkage and integration, as well as the construction of a hierarchical diagnosis and treatment system, were put forward. Suggestions such as construction according to local conditions, strengthening internal coordination, and optimizing external guarantee were put forward, so as to provide practical reference for the in-depth promotion of other national regional medical center construction projects.