ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Objective To systematically review the incidence of antibiotic-associated diarrhea(AAD)in critically ill patients in China,and to provide evidence-based basis for the rational use of antibiotics.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP and SionMed databases were electronically searched to collect studies on the incidence of AAD in acute and critically ill patients in China from inception to April 23,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed using Stata 17.0 software.Results A total of 50 studies involving 26,512 subjects were included.Meta-analysis results showed that the incidence of AAD in critically ill patients in China was 26.5%[95%CI(22.9%,30.1%)].Subgroup analysis showed that the incidence of AAD in critically ill children in China was 40.6%[95%CI(30.7%,50.4%)],and in critically ill adults in China was 18.7%[95%CI(16.1%,21.4%)],among which the incidence of AAD in children in East China and adults in Southwest China was the lowest.The incidence of AAD in children and adults in Northeast China was the highest.Conclusion The incidence of AAD in critically ill patients in China is relatively high,and it is necessary to carry out effective intervention measures,such as rational selection and standardized use of antibiotics,early prevention and detection of AAD occurrence,to reduce the medical burden caused by AAD in critically ill patients and improve the quality of prognosis.

Objective To evaluate the quality of Xi xiong(Gansu Chuanxiong)based on the combination of intelligent sensory technology,HPLC and HS-SPME-GC-MS.Methods The chromaticity values of 10 batches of Gansu Chuanxiong Rhizoma samples were measured using a colorimeter and clustering analysis was performed;an electronic nose was used to measure the odor of Gansu Chuanxiong Rhizoma,and Loadings and PCA were conducted;According to the method under the Chuanxiaong Rhizoma section of the Chinese Pharmacopoeia,the moisture,ash content and extract were determined;HPLC was used to determine the contents of ferulic acid,chlorogenic acid and ligustrazine;the volatile components were analyzed by HS-SPME-GC-MS;the quality of Gansu Chuanxiong Rhizoma was evaluated by analyzing the correlation between chromaticity value,odor and active components.Results The total color value of Gansu Chuanxiong Rhizoma ranged from 31.210 1±1.193 7 to 43.976 3±0.721 4,at the Euclidean distance of 10,and the 10 batches of Gansu Chuanxiong Rhizoma could be clustered into four categories;Loadings and PCA showed that the higher contribution of sensors W2S,W5S,W2W,W1W and W1S to Gansu Chuanxiong Rhizoma samples,the variance contribution of the first and second principal components was 62.6%and 22.4%,respectively;water,ash and extract in 10 batches of Gansu Chuanxiong Rhizoma all met the standards of Chinese Pharmacopoeia;the HPLC determination results indicated that the content of ferulic acid in Gansu Chuanxiong Rhizoma was greater than 0.192 6%,ligustrazine content was between 0.001 2%and 0.006 1%,chlorogenic acid content was greater than 0.016 4%;HS-SPME-GC-MS results indicated 52 volatile components were identified in Gansu Chuanxiong Rhizoma samples,the olefin compounds were rich in species,phenyphthalide compounds had the highest relative content;the correlation analysis showed that the color values ΔL*,Δb* and ΔE showed a high degree of correlation with ferulic acid and ligusticum tecidate A.Conclusion This study clarifies the intrinsic quality of Gansu Chuanxiong Rhizoma and provides a theoretical basis for research on Gansu Chuanxiong Rhizoma.

Objective To explore the role of postdoctoral talent cultivation in high-quality development of public hospi-tals.Methods The data of 165 postdoctoral fellows were analyzed from Zhongshan Ophthalmology Center,Sun Yat-sen Univer-sity over the past decade.The analysis involved examining the entire management process from recruitment to completion,inclu-ding the improvement of relevant systems,evaluation standards,implementation of hierarchical management,mentor-student in-teractions,and academic exchanges,as well as studying the quality enhancement of the postdoctoral talent pool,research output,and employment analysis.Results The standardized management of whole postdoctoral cultivation process and the continuous improvement of systems significantly enhanced the achievements of postdoctoral fellows in research,publications,and commer-cialization of the scientific and research findings.For instance,from 2018 to 2022,the number of National Science Foundation-funded programs that the postdoctoral fellows obtained accounted for 26.7％of the total number,while the number of provincial and ministerial funded programs accounted for 73.3％.In 2020,the proportion of postdoctoral researchers who obtained the Na-tional Natural Science Foundation of China's Youth Program was 80％of the total.In 2021,the proportion of postdoctoral fellows who published papers with an impact factor of above 10 as the first author or co-first author was 45.83％.Conclusion The training of high-level medical postdoctoral talents is crucial for high-quality development of public hospitals,improving interdisci-plinary adaptability of postdoctoral fellows and collaborative mentorship awareness.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

Computational approaches,encompassing both physics-based and machine learning(ML)methodolo-gies,have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities.The human dopamine(DA)transporter(hDAT)is the primary therapeutic target of numerous psychi-atric medications.However,traditional hDAT-targeting drugs,which interact with the primary binding site,encounter significant limitations,including addictive potential and stimulant effects.In this study,we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape(WHALES)descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs.Initially,WHALES descriptors facilitated a similarity search,employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates.Consequently,from a compound library of 4,921 marketed and clinically tested drugs,we identified 27 candidate atypical inhibitors.Subsequently,ADMETlab was employed to predict the pharmacokinetic and toxi-cological properties of these candidates,while induced-fit docking(IFD)was performed to estimate their binding affinities.Six compounds were selected for in vitro assessments of neurotransmitter re-uptake inhibitory activities.Among these,three exhibited significant inhibitory potency,with half maximal inhibitory concentration(IC50)values of 0.753 μM,0.542 μM,and 1.210 μM,respectively.Finally,molecular dynamics(MD)simulations and end-point binding free energy analyses were con-ducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation.In conclusion,our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective To explore the genotoxicity of lead on DNA damage and the repair role of homologous recombination repair protein RAD51 in lead-induced DNA double-strand breaks in TK6 cells. Methods i) TK6 cells in the logarithmic growth phase were divided into five groups: blank control group, low-dose group, medium-dose group, high-dose group, and positive control group. The first four groups were treated with lead acetate at concentrations of 0, 120, 240 and 480 μmol/L, respectively. The positive control group was treated with 100 μmol/L hydrogen peroxide solution incubated on ice for 24 hours. After the positive rate of phosphorylated histone H2AX (γ-H2AX) was detected by immunofluorescence. Cell proliferation was detected by 5-ethynyl-2'-deoxyuridine (EDU) method. Cell cycle and apoptosis were detected by flow cytometry, and the relative expression of RAD51 protein was detected by Western blotting. ii) A short hairpin RNA (shRNA) silencing RAD51 model was constructed in TK6 cells, and the cells were divided into untreated group (normal TK6 cells), negative control group (sh-NC), and RAD51 silencing group (sh-RAD51). The mRNA expression of RAD51 was detected by real-time fluorescence quantitative polymerase chain reaction, and the protein expression of RAD51 was detected by Western blotting to verify the interference effect. iii) Normal TK6 cells, sh-NC, and sh-RAD51 were treated with 480 μmol/L lead acetate for 24 hours, and were divided into lead treatment group, lead+negative control group, and lead + RAD51 silencing group, respectively. Untreated normal TK6 cells was served as the control group. The positive rate of γ-H2AX and the expression of RAD51 protein in each group was detected by immunofluorescence and Western blotting, respectively. Results i) With the increase of lead acetate treatment concentration in TK6 cells, the positive rate of γ-H2AX increased (all P<0.05), the proportion of EDU positive cells decreased (all P<0.05), and the proportion of S-phase cells decreased (all P<0.05). The proportion of G1-phase cells in the high-dose group and the positive control group was higher than those in the low- and medium-dose groups (all P<0.05). The proportion of G2-phase cells in the medium-dose group, high-dose group, and positive control group increased compared with the blank control group (all P<0.05), although no significant differences were observed among these three dosing groups (all P>0.05). The apoptosis rate and the relative expression of RAD51 protein of TK6 cells in each group increased with the increase of lead acetate concentration (all P<0.05). ii) The relative expression levels of RAD51 mRNA and protein in the RAD51 silencing group were lower than those in the untreated group and the negative control group (all P<0.05) after RAD51 silencing. iii) The positive rate of γ-H2AX in the lead + RAD51 silencing group increased (all P<0.05), and the relative expression of RAD51 protein decreased (all P<0.05),compared with the control group, lead treatment group, and lead + negative control group. Conclusion Lead exposure induces DNA double-strand breaks in TK6 cells, inhibits cell proliferation, and causes cell cycle arrest and apoptosis in a dose-effect manner. Downregulation of the RAD51 gene can lead to inhibition of the homologous recombination repair pathway, thereby increasing the TK6 cell sensitivity to lead-induced DNA damage.

Objective:To investigate the interventional effect of Rhizoma Corydalis on mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),as well as the potential mechanism of Rhizoma Corydalis in the treatment of UC based on metabolomics and inflammation biomarkers.Methods:A mouse model of UC was established,and then the mice were divided into model group,high-dose group(1.517 g/kg crude drug),middle-dose group(0.986 g/kg crude drug),low-dose group(0.455 g/kg crude drug),and positive drug group(5-aminosalicylic acid at a dose of 718.8 mg/kg),while the mice without modeling were selected as normal group(0.9%NaCl by gavage).The mice in each group were administered for 7 consecutive days,and phenotypic parameters were dynamically moni-tored,such as body weight change,disease activity index(DAI),mean daily food intake,and daily water intake.The mice were sacri-ficed after 7 days to collect serum and colon tissue samples;ELISA was used to measure the serum levels of the proinflammatory fac-tors interleukin-6(IL-6),interleukin-17A(IL-17A),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α),and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was used to perform the non-targeted metabolomics analysis and compare the differences in se-rum metabolite profiles between groups.The mice were selected for modeling and validation with the same method,and glutathione(GSH)was selected as the positive drug.Colon length and mucosal damage were assessed,and quantitative real-time PCR was used to measure the relative mRNA expression levels of the key genes in the glutathione synthesis pathway(γ-glutamylcysteine synthetase[γ-GCS]and oxidative stress regulators yap1p and skn7)and mito-chondrial GSH transporter protein(Slc25a39)in colonic tissue.Results:Rhizoma Corydalis significantly improved weight loss,DAI,and colon length in a dose-dependent manner in the model animals,and there were reductions in the serum levels of IL-6,CRP,and TNF-α,while it had no significant effect on IL-17A.The metabolomics analysis revealed 21 potential biomarkers associated with amino acid and lipid metabolism,which were significantly regulated by Rhizoma Corydalis.In the verification experiment,both Rhi-zoma Corydalis and GSH exerted a significant protective effect against colonic mucosal damage without affecting colon length.Rhizoma Corydalis upregulated the expression of genes associated with glutathione synthesis,especially γ-GCS,suggesting that Rhizoma Co-rydalis could enhance intestinal antioxidant defenses.Conclusion:Rhizoma Corydalis has a therapeutic potential in a mouse model of DSS-induced UC and can alleviate symptoms,reduce the serum levels of inflammatory markers,and regulate metabolic pathways,and upregulation of the genes associated with glutathione synthesis suggests that the drug can enhance intestinal antioxidant defenses.