Depression is a common mental disorder that falls under the category of "stagnation syndrome" in traditional Chinese medicine （TCM）. Its complex pathogenesis poses challenges for the development of novel therapeutic agents. Currently， clinically used antidepressants are often accompanied by significant side effects， and statistics show that about one-third of patients do not respond to these medications. TCM demonstrates advantages in the treatment of depression through multi-target， multi-pathway and multi-mechanistic approaches. Pinelliae Rhizoma， a phlegm-resolving herb， exhibits effects such as drying dampness and resolving phlegm， as well as eliminating stuffiness and reducing masses. The characteristics of harmonizing Yin and Yang and resolving stagnation in the middle energizer align precisely with the pathogenesis of depression syndrome， demonstrating therapeutic efficacy in affected patients. Literature studies have found that the active ingredients of Pinelliae Rhizoma， such as cavidine， baicalein， β-sitosterol， as well as Pinelliae Rhizoma herb pairs， such as Pinelliae Rhizoma-Magnoliae Officinalis Cortex， Pinelliae Rhizoma-husked sorghum， Pinelliae Rhizoma-Prunellae Spica， exhibit significant antidepressant effects. Furthermore， TCM formulas containing Pinelliae Rhizoma as the principal therapeutic agent， such as Banxia Xiexin Tang， Banxia Houpo Tang， and Wendan Tang， as well as formulas incorporating Pinelliae Rhizoma like compound Xiaochaihu Tang， Chaihu Jia Longgu Muli Tang， and Erchen Tang， have also demonstrated favorable antidepressant efficacy. The antidepressant mechanism of these agents may involve modulation of 5-hydroxytryptamine （5-HT） and dopamine （DA） levels， up-regulation of brain-derived neurotrophic factor （BDNF） expression， regulation of the hypothalamus-pituitary-adrenal （HPA） axis， reduction of oxidative stress， modulation of nuclear transcription factor-κB （NF-κB） signaling pathway， and inhibition of microglia-mediated inflammatory responses. This review summarized the antidepressant mechanisms and clinical applications of the active components， herb pairs， and TCM formulas containing Pinelliae Rhizoma， aiming to provide a reference for modern research on the use of Pinelliae Rhizoma in antidepressant therapy.

OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

Meconium is changed from defoliated intestinal villi with apoptosis. A meconium corpuscle is a limited architecture in the meconium at the light microscopic level. In histological and immunohistochemical sections of the abdomen from 40 fetuses at 20–31 weeks of gestation, we found 12 fetuses with meconium and examined the architecture.A solid or loose meconium was seen depending on sites. The solid meconium in the colon and rectum contained numerous spherical or rugby ball-like corpuscles comprising of a core with tightly-packed atrophied cells and a laminar fibrous sheath.The solid meconium surrounded and incorporated villi that maintained the original architecture. The loose meconium was seen not only in the stomach and duodenum but also, depending on specimens, in the colon and rectum. It was composed of a large mucosal fold, a single small villus and/or fragmented epithelia. Notably, these mucosal tissues still contained chromogranin-positive gastrointestinal cells and cytokeratin-positive epithelia. A large ring-like meconium was composed of the entirely circular mucosa or epithelia that seemed to be detached along the muscularis mucosae or the basal lamina.A sheath-like fibrous structure in meconium seemed to originate from the lamina propria and basal lamina of villi. A defoliation of villi with apoptosis seemed difficult to explain a detachment of the entirely circular mucosa or epithelia in large fetuses examined. The latter event might require a specific mechanism such as an in utero intussusception in which a proximal side of the colon was invaginated into the distal lumen.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Liver cancer (LC) remains one of the most prevalent tumors globally. Despite considerable advancements in its clinical treatment in recent years, the global burden of this disease is projected to increase. According to World Health Organization statistics, the number of LC deaths worldwide in 2022 was 760,000, ranking third among all cancers. Therefore, there is an urgent need to delve deeper into the realms of LC diagnosis, prognosis, and treatment. Proteomics, as an emerging technology leveraging mass spectrometry (MS)-based protein identification, liquid chromatography separation, and bioinformatics-driven data integration, enables the systematic characterization of proteome dynamics to address critical challenges in LC research. These challenges include the discovery of diagnostic and prognostic biomarkers as well as therapeutic targets. By scrutinizing the expression of specific proteins in both normal and cancerous tissues through high-throughput protein microarrays, researchers can uncover novel biomarkers. The use of these biomarkers alone or in combination with established ones holds the potential to significantly advance the fields of LC diagnosis, prognosis, and treatment. In general, the application of proteomics has significantly promoted the development of LC research. In this review, we summarized the latest advancements in the application of proteomics in LC, with a particular focus on diagnosis, prognosis, and treatment. We also concluded selected protein markers, aiming to offer guidance for further applications and present additional therapeutic targets for LC.

ObjectiveTo evaluate the immediate effectiveness and safety of four intranasal acupuncture methods based on different intranasal localizations of Neiyingxiang （EX-HN 9） for improving nasal ventilation in patients with allergic rhinitis （AR）. MethodsA total of 120 patients with AR were randomly divided into four groups with 30 cases in each group， the agger nasi group， the inferior turbinate-alar junction group， the inferior turbinate top group， and the nasal septum group. All patients received one 20-minute session of intranasal acupuncture. The agger nasi group received acupuncture at the agger nasi site， the inferior turbinate-alar junction group at the junction of the inferior turbinate and alar cartilage， the inferior turbinate top group at the top of the inferior turbinate directly facing the nostril， and the nasal septum group at Little's area of the nasal septum. Before acupuncture and within 5 min after treatment， the assessments and measurements were performed including nasal obstruction symptom evaluation （NOSE） scale used to evaluate the severity of nasal obstruction before and after acupuncture， a nasal resistance/nasal flow analyzer applied to detect nasal airway resistance （NAR） and nasal respiration volume （NS）， the visual analogue scale （VAS） adopted to assess pain intensity. The incidence of nasal bleeding and other adverse events were recorded， and patients' willingness to receive repeat treatment was statistically analyzed. ResultsCompared with baseline within group， all four groups showed decreased NOSE scores and NAR as well as elevated NS after treatment （all P＜0.05）. Compared with the agger nasi group and the inferior turbinate-alar junction group， the inferior turbinate top group had higher NOSE scores and lower NS； the nasal septum group presented higher NOSE scores and NAR alongside lower NS （P＜0.05）. The nasal septum group yielded significantly higher VAS scores than the other three groups （P＜0.05）， with 11 cases （36.67%） of massive nasal bleeding observed， while no severe nasal hemorrhage occurred in the remaining groups. The proportions of patients willing to receive repeated intranasal acupuncture treatment were 70.00% （21/30） in the agger nasi group， 76.67% （23/30） in the inferior turbinate-alar junction group， 43.33% （13/30） in the inferior turbinate top group， and 3.33% （1/30） in the nasal septum group， respectively， with statistical significant difference among groups （χ² = 39.91， P＜0.001）. ConclusionAll four intranasal acupuncture methods can immediately improve nasal ventilation in patients with AR. The agger nasi group and inferior turbinate-alar cartilage junction group achieved superior therapeutic improvement compared with the inferior turbinate top group and nasal septum group， accompanied by better safety and higher patient acceptability.

ObjectiveTo evaluate the immediate effectiveness and safety of four intranasal acupuncture methods based on different intranasal localizations of Neiyingxiang （EX-HN 9） for improving nasal ventilation in patients with allergic rhinitis （AR）. MethodsA total of 120 patients with AR were randomly divided into four groups with 30 cases in each group， the agger nasi group， the inferior turbinate-alar junction group， the inferior turbinate top group， and the nasal septum group. All patients received one 20-minute session of intranasal acupuncture. The agger nasi group received acupuncture at the agger nasi site， the inferior turbinate-alar junction group at the junction of the inferior turbinate and alar cartilage， the inferior turbinate top group at the top of the inferior turbinate directly facing the nostril， and the nasal septum group at Little's area of the nasal septum. Before acupuncture and within 5 min after treatment， the assessments and measurements were performed including nasal obstruction symptom evaluation （NOSE） scale used to evaluate the severity of nasal obstruction before and after acupuncture， a nasal resistance/nasal flow analyzer applied to detect nasal airway resistance （NAR） and nasal respiration volume （NS）， the visual analogue scale （VAS） adopted to assess pain intensity. The incidence of nasal bleeding and other adverse events were recorded， and patients' willingness to receive repeat treatment was statistically analyzed. ResultsCompared with baseline within group， all four groups showed decreased NOSE scores and NAR as well as elevated NS after treatment （all P＜0.05）. Compared with the agger nasi group and the inferior turbinate-alar junction group， the inferior turbinate top group had higher NOSE scores and lower NS； the nasal septum group presented higher NOSE scores and NAR alongside lower NS （P＜0.05）. The nasal septum group yielded significantly higher VAS scores than the other three groups （P＜0.05）， with 11 cases （36.67%） of massive nasal bleeding observed， while no severe nasal hemorrhage occurred in the remaining groups. The proportions of patients willing to receive repeated intranasal acupuncture treatment were 70.00% （21/30） in the agger nasi group， 76.67% （23/30） in the inferior turbinate-alar junction group， 43.33% （13/30） in the inferior turbinate top group， and 3.33% （1/30） in the nasal septum group， respectively， with statistical significant difference among groups （χ² = 39.91， P＜0.001）. ConclusionAll four intranasal acupuncture methods can immediately improve nasal ventilation in patients with AR. The agger nasi group and inferior turbinate-alar cartilage junction group achieved superior therapeutic improvement compared with the inferior turbinate top group and nasal septum group， accompanied by better safety and higher patient acceptability.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease worldwide, accounting for 20%-40% of primary glomerulonephritis cases. Approximately 40% of patients progress to end-stage renal disease within 20 years. Traditional treatments primarily involve renin-angiotensin system inhibitors and glucocorticoids, but some patients show limited response and face infection risks. In recent years, the dual-target biologic agent Telitacicept, which targets B cell-activating factor/B lymphocyte stimulator(BAFF/BLyS) and a proliferation-inducing ligand (APRIL), has demonstrated significant potentialin the treatment of IgAN. By simultaneously neutralizing BAFF/BLyS and APRIL, Telitacicept suppresses abnormal B-cell activation and the production of pathogenic IgA1, significantly reducing urinary protein levels and preserving renal function. This article systematically reviews its mechanism of action, clinical efficacy, and safety, aiming to provide insights for the clinical management of IgAN.

Alzheimer's disease(AD)is the leading cause of dementia,and no effective treatment has been devel-oped for it thus far.Recently,the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions.Accordingly,the potential therapeutic effect of pterostilbene(PTS)on AD has been demonstrated in multiple in vivo and in vitro experiments.In this study,we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD.Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms,including anti-oxidative damage,anti-neuroinflammation,anti-apoptosis,cholinesterase activity inhibition,attenuation of β-amyloid deposi-tion,and tau protein hyperphosphorylation.Moreover,PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha(PPAR-α),monoamine oxi-dase B(MAO-B),silent information regulator sirtuin 1(SIRT1),and phosphodiesterase 4A(PDE4A).Furthermore,to further elucidate the potential therapeutic mechanisms of PTS in AD,we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins,and the obtained binding energies ranged from-2.83 to-5.14 kj/mol,indicating that these proteins exhibit good binding ability with PTS.Network pharmacology analysis revealed multiple po-tential mechanisms of action for PTS in AD.In summary,by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD,it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD,either using PTS or other developed drug interventions.

Structural optimization of lead compounds is a crucial step in drug discovery.One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties.One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules,thereby accelerating the molecular optimization process.Deep molecular diffusion generative models simulate a gradual process that creates novel,chemically feasible molecules from noise.However,the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules,leading to challenges in modifying the scaffold-based molecular structures,and creates limitations in the stability and diversity of the generated molecules.To address these challenges,we propose a deep molecular diffusion generative model,the three-dimensional(3D)equivariant diffusion-driven molecular generation(3D-EDiffMG)model.The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder(dual-SWLEE)is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions.Addi-tionally,a gate multilayer perceptron(gMLP)block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies.The experimental results show that 3D-EDiffMG effectively generates unique,novel,stable,and diverse drug-like molecules,highlighting its potential for lead optimization and accelerating drug discovery.