Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

ObjectiveTo explore the role and mechanism of Hei Xiaoyaosan in regulating the protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway in cascade modulation of oxidative stress and apoptosis for preventing and treating Alzheimer's disease （AD）. MethodsNinety male SD rats of 4 months old were randomly assigned into a control group （n=10）， a sham group （with injection of 1 μL normal saline into bilateral hippocampi， n=10）， and a modeling group （with injection of 1 μL beta-amyloid 1-42 solution into bilateral hippocampi to induce AD， n=70）. One week after modeling， 50 successfully modeled rats were selected and randomly allocated into model， donepezil hydrochloride （0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs once daily for six consecutive weeks. The Morris water maze was used to assess the learning and memory abilities of rats. Hematoxylin-eosin （HE） staining was performed to reveal hippocampal morphological changes in AD rats. Apoptosis in the hippocampal CA3 region was detected by terminal-deoxynucleotidyl transferase-mediated Nick end labeling. Immunofluorescence was used to visualize the expression of neuronal nuclear antigen （NeuN） in the CA1 region. Additionally， enzyme-linked immunosorbent assay was performed to assess the activities of glutathione peroxidase （GSH-Px）， glutathione-S-transferase （GST）， and catalase （CAT） in the hippocampus. Real-time PCR was conducted to measure the mRNA levels of Akt， GSK-3β， Nrf2， and HO-1， while Western blot was employed to determine the protein levels of phosphorylated Akt （p-Akt）/Akt， phosphorylated GSK-3β （p-GSK-3β）/GSK-3β， Nrf2， and HO-1. ResultsCompared with the control group， the model group on day 5 showed an increase in total swimming distance （P<0.01）， a reduction in the percentage of time spent in the target quadrant （P<0.01）， reduced and disarranged neurons， nuclear condensation， varying degrees of cellular damage， increased apoptosis of hippocampal neurons （P<0.01）， decreased NeuN content （P<0.01）， weakend activities of GSH-Px， GST， and CAT （P<0.01）， and down-regulated mRNA levels of Nrf2 and HO-1 （P<0.01） and protein levels of p-Akt/Akt， p-GSK-3β/GSK-3β， Nrf2， and HO-1 （P<0.01） in the hippocampus. Compared with the model group， donepezil hydrochloride and high， medium， and low doses of Hei Xiaoyaosan shortened the total swimming distance on day 5 （P<0.05， P<0.01）， increased the percentage of time spent in the target quadrant （P<0.05， P<0.01）， improved the arrangement and morphology of neurons， reduced nuclear condensation and the apoptosis rate of hippocampal neurons （P<0.01）， increased the NeuN content （P<0.01）， enhanced the activities of GSH-Px， GST， and CAT （P<0.05， P<0.01）， and up-regulated the mRNA levels of Nrf2 and HO-1 （P<0.05， P<0.01） and the protein levels of p-Akt/Akt， p-GSK-3β/GSK-3β， Nrf2， and HO-1 （P<0.05， P<0.01） in the hippocampus. ConclusionHei Xiaoyaosan can regulate the Akt/GSK-3β/Nrf2/HO-1 pathway to enhance the antioxidant stress capacity and inhibit neuron apoptosis to exert the neuroprotective effect， thereby ameliorating the cognitive dysfunction and pathological damage in AD rats.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Hei Xiaoyaosan on cognitive impairment and the histone deacetylase sirtuin-1 （SIRT1）/tumor suppressor p53/solute carrier family 7 member 11 （SLC7A11） signaling pathway in the rat model of Alzheimer's disease （AD）. MethodsA total of 90 16-week-old SPF-grade SD male rats were randomly assigned in a blank group （n=10）， a sham group （n=10， with injection of 1 μL normal saline into the bilateral hippocampi）， and an AD modeling group （n=70， with injection of 1 μL β amyloid 1-42 solution into the bilateral hippocampi）. According to the random number table method， fifty successfully modeled rats were assigned into model， donepezil hydrochloride （0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， and they were administrated with corresponding agents via gavage once a day for 42 consecutive days. Morris water maze test was carried out to examine the cognitive function of rats. Nissl staining was employed to observe the morphology of hippocampal neurons in each group， and Prussian blue staining was used to detect iron deposition in the hippocampal tissue. Biochemical kits were used to measure the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and iron ion （Fe²⁺） in the hippocampal tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA levels， respectively， of SIRT1， p53， SLC7A11， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long-chain family member 4 （ACSL4） in the hippocampus. ResultsCompared with the blank group， the model group showed reductions in target quadrant movement distance （P<0.01） and target quadrant residence time （P<0.05）， disarrangement of hippocampal neurons， increased ferroptosis deposition in the hippocampus， a lowered level of SOD， risen levels of MDA and Fe²⁺ （P<0.05， P<0.01）， down-regulated protein and mRNA levels of SIRT1， SLC7A11， and GPX4 （P<0.05， P<0.01）， up-regulated protein and mRNA levels of p53 and ACSL4 （P<0.01）， and aggravated pathological process of AD. Compared with the model group， donepezil hydrochloride extended the target quadrant residence time and the target quadrant movement distance （P<0.05， P<0.01）. High- and medium- doses of Hei Xiaoyaosan extended the target quadrant residence time and the target quadrant movement distance （P<0.05， P<0.01）， improved the neuron arrangement and reduced the ferroptosis deposition in the hippocampus， elevated the SOD level， lowered the MDA and Fe²⁺ levels （P<0.05， P<0.01）， up-regulated the protein and mRNA levels of SIRT1， SLC7A11， and GPX4 （P<0.01， P<0.05）， and down-regulated the protein and mRNA levels of p53 and ACSL4 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can regulate the SIRT1/p53/SLC7A11 signaling pathway to mitigate oxidative stress and inhibit ferroptosis， thereby ameliorating the cognitive dysfunction in AD rats.

Objective To explore predictive factors of severe community-acquired pneumonia (CAP) complicated with respiratory failure (RF) and to develop and internally validate a clinical prediction model. Methods A retrospective study was conducted on 350 patients with severe CAP admitted to Tianyou Hospital Affiliated to Wuhan University of Science and Technology from September 2022 to December 2024. Patients were randomly divided into a training set (n＝245) and a validation set (n＝105) in a 7∶3 ratio, and further categorized into RF and non-RF groups. LASSO regression was applied to optimize variable selection. Multivariate logistic analysis was used to construct the prediction model, followed by internal validation. Results Univariate regression analysis identified male, hypertension, diabetes, coronary heart disease, age, CURB-65 score, white blood cell count, neutrophil count, C-reactive protein (CRP), serum amyloid A, procalcitonin, and hospital stay as risk factors for RF in severe CAP, while albumin level was a protective factor. LASSO regression selected CURB-65 score, albumin level, and CRP for inclusion in the final model. The area under the receiver operating characteristic curve was 0.903 in the training set and 0.919 in the validation set. Calibration curve analysis demonstrated excellent agreement between predicted and observed probabilities in both sets, and Hosmer-Lemeshow goodness-of-fit tests indicated no significant deviations. Threshold probabilities ranged from 0.01 to 0.99 in both training and validation sets. Conclusions CURB-65 score, albumin level, and CRP are independent predictors of RF in severe CAP. The clinical prediction model based on these factors exhibits strong discrimination, calibration, goodness-of-fit, and clinical utility.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional