This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

The high pathogenicity and mortality of respiratory viral infections pose a significant clinical burden.Due to the high de-gree of variability of viral proteins,some current targeted drugs are highly susceptible to drug resistance,and there is an urgent need for the development of effective therapeutic strategies.Glycoconjugates are widely distributed in hosts and viruses,and participate in host-virus interactions,viral replication,innate and adaptive immunity,etc.Aberrant glycosylation is involved in the pathogenesis of a vari-ety of diseases,and anti-respiratory viral strategies targeting glycosylation have the advantages of high specificity,low drug resistance,and broad-spectrum.In recent years,traditional Chinese medicines(TCMs)have shown unique potential in intervening in glycosylation-related antiviral fields due to their multi-target regulatory properties.The aim of this paper is to focus on the biological functions of glycosylation modifications,the research progress of virus infection and potential TCM monomers targeting glycosylation,which not only reveals the scientific connotation of TCM regulation of glycosylation,but also provides a natural molecular library for the development of novel antiviral strategies based on glycosylation intervention.In the future,it is necessary to further combine the tech-niques of glycomics and structural biology to elucidate the precise mechanism of spatial and temporal dynamics of TCM monomers in regulating glycosylation,and to promote the modernization of TCM.

Ischemic stroke(IS),caused by the interruption of cerebral blood flow,results in localized ischemia and hypoxia in the brain tissue.Its pathophysiological mechanisms are complex,involving disturbances in energy metabo-lism,oxidative stress,inflammation,and apoptosis.As the cell's powerhouse,mitochondria play a critical role in IS,and their dysfunction exacerbates neuronal injury.In recent years,tunneling nanotubes(TNTs),a novel form of intercellular communication,have gained increasing attention for their role in mediating the intercellular transfer of functional mito-chondria.Studies have shown that both stem cells and astrocytes can transfer healthy mitochondria to damaged neurons via TNTs,thereby restoring energy metabolism,reducing apoptosis,and alleviating neurological deficits.This review summa-rizes the current research on the mechanisms and biological functions of TNT-mediated mitochondrial transfer and discuss-es its potential therapeutic applications in IS,aiming to provide insight into IS treatment strategies.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective: To investigate the distribution of HPA, HLA alleles and haplotypes among apheresis platelet donors in Changsha, China, and to establish an apheresis platelet donor database. Methods: High-resolution genotyping of HLA-A and -B was performed using PCR sequence based typing (SBT) and next generation sequencing (NGS). HPA genotyping was conducted using quantitative PCR (Q-PCR). The allele frequency, haplotype frequency and linkage disequilibrium parameters were calculated using the direct counting method, the maximum likelihood method and Arlequin software (V 3.1). Results: A total of 41 HLA-A alleles and 82 HLA-B alleles were detected, and 457 HLA-A-B haplotypes were found, of which 25 showed strong linkage disequilibrium (RLD>0.50). The HPA-3 and HPA-15 had the highest HPA polymorphism and antigen mismatch rate in apheresis platelet donor database in Changsha, and the dual antigen mismatch rate was 0.3704 and 0.3743, respectively. Conclusion: The polymorphism of apheresis platelet donor database in Changsha is complex and has strong regional characteristics. Establishing a high-resolution donor database will strongly support the provision of genetically matched platelets for clinical use, facilitating precise platelet transfusion therapy.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

Objective To explore the mechanism of Angong Niuhuang pill on the neurological function of rats with spontaneous intracerebral hemorrhage based on the tumor necrosis factor-α/nuclear factor-κB(TNF-α/NF-κB)signaling pathway combined with network pharmacology.Methods The targets for treatment of intracerebral hemorrhage with Angong Niuhuang pill were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),High-Throughput Experiment and Refeence-guided Database of Traditional Chinese Medicine(HERB).Key targets were screened for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and molecular docking.Then,rats were randomly divided into normal control group,model group,Angong Niuhuang pill group(administered by gavage at 270 mg·kg-1·d-1),and the Western medicine group(intraperitoneal injection of 4 500 mg·kg-1·d-1+furosemide 1.8 mg·kg-1·d-1),the dosage administered was the equivalent dose ratio calculated based on the body surface area for humans and animals.The intracerebral hemorrhage model was replicated by the autologous heart blood caudate nucleus injection method.After modeling,the neurological function behavior scores,brain tissue water content,pathological changes of brain tissue,blood-brain barrier permeability,and protein expression levels of NF-κB p65,tumor necrosis factor receptor 1(TNFR1),inhibitor NF-κBα(IκBα)and TNF-α in brain tissue of each group were observed.Results A total of 216 intersection genes were selected.The results of GO enrichment analysis and KEGG pathway annotation analysis predicted that the TNF-α/NF-κB inflammatory signaling pathway was one of the main regulatory pathways.The animal experiment results showed that at 72 hours after modeling,compared with the model group,the neurological function score,brain tissue water content,and blood-brain barrier permeability index evans blue(EB)content of the Angong Niuhuang pill group were significantly decreased[neurological function score:1.62±0.62 vs.2.23±0.58,brain water content:(77.7±0.49)%vs.(79.9±0.04)%,EB content(μg/L):490.50±100.79 vs.1 966.20±94.81,all P<0.05];the pathological observation of brain tissue showed that Angong Niuhuang pill could reduce the pathological damage of brain tissue around the hematoma,repair the blood-brain barrier,and alleviate brain edema;the Western blotting results showed that Angong Niuhuang pill could inhibit the protein expression of TNF-α,TNFR1,and NF-κB p65 in brain tissue[NF-κB p65 protein expresion(NF-κB p65/β-actin):2.27±0.52 vs.5.40±0.26;TNFR1 protein expression(TNFR1/β-actin):1.49±0.33 vs.2.52±0.04,TNF-α protein expression(TNF-α/β-actin):1.40±0.13 vs.2.29±0.18,all P<0.05],promote the protein expression of IκB-α(IκB-α/β-actin):0.78±0.02 vs.0.32±0.00,P<0.05).Conclusion Angong Niuhuang pill may regulate the TNF-α/NF-κB signaling pathway by inhibiting the expression of TNFR1 and promoting the expression of IκB-α,exerting neuroprotective effects.

Objective:To evaluate the effect of multiple sevoflurane anesthesia on the metabolism of long-chain fatty acids in the hippocampus of newborn mice and the role of peroxisome proliferator-activated receptor-beta (PPARβ).Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, weighing 3-5 g, were divided into 2 groups ( n=8 each) by a random number table method: control group (group C) and multiple sevoflurane anesthesia group (group S). This study was performed in 2 parts. PartⅠ Sixteen newborn mice were divided into 2 groups ( n=8 each) using a random number table: control group (C group) and multiple sevoflurane anesthesia group (S group). Anesthesia was performed with sevoflurane on postnatal days 6, 7 and 8. The hippocampus was obtained at postnatal day 9 for determination of the content of long-chain fatty acids (by ultra-high performance liquid mass spectrometry), expression of PPARβ (by Western blot), and expression of stearoyl-CoA desaturase-2 (Scd2) and fatty acid desaturase 2 (Fads2) mRNA (using quantitative real-time polymerase chain reaction). Part Ⅱ Twenty-one newborn mice were divided into 3 groups ( n=7 each) using a random number table: control+ normal saline group (group C+ S), sevoflurane + normal saline group (group S+ S), and sevoflurane+ PPARβ specific agonist KD3010 group (group S+ K). Anesthesia was carried out with sevoflurane on postnatal days 6, 7 and 8. KD3010 25 mg/kg was intraperitoneally injected once a day from postnatal day 6 to 13 in S+ K group. The novel object recognition test was performed on postnatal day 37, and the Morris water maze test was performed on postnatal day 42. The hippocampal tissues were obtained on postnatal day 47 for detection of the expression of Scd2 mRNA and Fads2 mRNA by fluorescent quantitative real-time polymerase chain reaction. Anesthesia was carried out with sevoflurane as follows: Mice were exposed to 3% sevoflurane in 40% oxygen-60% nitrogen in an induction chamber for 2 h at a flow rate of 1 L/min. Results:PartⅠ Compared with group C, the total content of long-chain fatty acids, contents of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids were significantly decreased, the percentage of saturated fatty acids was increased, the percentage of monounsaturated fatty acids and polyunsaturated fatty acids was decreased, the expression of Scd2 mRNA and Fads2 mRNA was down-regulated, and the expression of PPARβ was down-regulated in group S ( P<0.05). Part Ⅱ Compared with group C+ S, the discrimination index in the novel object recognition test and percentage of time spent in the target quadrant were significantly decreased, the number of crossing the original platform was reduced, and the expression of Scd2 and Fads2 mRNA was down-regulated in group S+ S ( P<0.05). Compared with group S+ S, the discrimination index in the novel object recognition test and percentage of time spent in the target quadrant were significantly increased, the number of crossing the original platform was increased, and the expression of Scd2 and Fads2 mRNA was up-regulated in group S+ K ( P<0.05). Conclusions:Multiple anesthesia with sevoflurane can lead to the disorder of long-chain fatty acid metabolism in the hippocampus of neonatal mice, resulting in long-term cognitive dysfunction. The mechanism may be related to inhibiting the activity of hippocampal PPARβ signaling pathway.