ObjectiveTo investigate the effect and mechanism of Polygonatum neutral polysaccharides from sibiricum （PSP-NP） on colon injury in mice with chronic obstructive pulmonary disease （COPD）. MethodsMale C57BL/6J mice were randomly divided into a control group， a COPD model group， and a PSP-NP group. The COPD model was established using smoke exposure combined with intranasal LPS administration. The PSP-NP group was simultaneously treated daily with 200 mg/kg of PSP-NP via intragastric gavage， while the other groups received an equal volume of saline. HE staining was used to observe the pathological changes in the colon. ELISA was employed to detect the levels of LPS in serum and the expressions of ZO-1， Occludin， IL-6， and TNF-α in colon tissue. UPLC-MS was used to detect the types and contents of bile acids in colonic content， and to screen for differential bile acids. Differential microbial flora were identified using 16S rRNA gene sequencing， and correlation analysis was conducted with differential bile acids. PSP-NP was combined with the differential bile acids cholic acid （CA）， and deoxycholic acid （DCA） in vitro to analyze the binding capacity of PSP-NP for CA and DCA. PSP-NP was applied to NCM460 normal colonic epithelial cells cultured in CA and DCA. Cell migration ability was assessed using the scratch assay， and the mRNA expression levels of inflammatory cytokines TNF-α， IL-6， and NF-κB were measured by RT-qPCR. ResultsPSP-NP effectively improved colonic damage in COPD model mice， enhanced mechanical barrier function， alleviated inflammatory response， and regulated abnormal changes in colonic flora and bile acid metabolism. Correlation analysis further revealed that PSP-NP regulated colonic bile acid metabolism and reduced the redundancy of secondary bile acids by increasing the relative abundance of Bacteroidota， Verrucomicrobiota， Bacteroides， and Akkermansia， while decreasing the relative abundance of Lactobacillus and Bifidobacterium. Notably， in vitro binding assays demonstrated that PSP-NP bound to differential bile acids DCA and CA， with the strongest binding capacity for DCA at 58.2%. In cellular functional studies， DCA inhibited the migration ability of colonic epithelial cells NCM460 and significantly increased the relative mRNA expression levels of inflammatory factors TNF-α， IL-6， and NF-κB. Importantly， co-treatment with PSP-NP significantly ameliorated the impact of DCA on NCM460 cells. ConclusionsPSP-NP may significantly improve colonic damage in COPD model mice. The mechanism may involve the regulation of colonic bile acid metabolism and bile acid profiles through both microbial modulation and direct binding， thereby reducing the damage caused by secondary bile acids such as DCA to colonic epithelial cells.

Background The affinity between placental transporters and perfluoroalkyl substances (PFAS) could affect the placental transport and toxicity of PFAS, while the study on the interaction between PFAS and placental transporters is limited. Objective To explore interactions between PFAS and placental transporters using molecular docking, and to provide a theoretical basis for PFAS toxicity prediction and fetal health risk assessment. Methods Fifteen PFAS compounds, each conformationally sampled and energy-minimized, and 16 placental transporters, represented by their 3D structures, were imported into a molecular docking software (MOE 20140901). For each PFAS, 30 distinct conformations were generated and docked into the active pockets of the transporters using a semi-flexible docking mode. Docking poses were primarily scored and ranked based on their calculated binding free energy (ΔG, kcal·mol⁻¹), with additional consideration given to hydrogen bonding interactions and the ligand's root mean square deviation (RMSD) at the binding site; the top 20 poses for each complex were subsequently output. Optimal binding configurations were identified as those exhibiting a relatively low binding free energy (ΔG ranging from −3 to −10 kcal·mol⁻¹), well-defined hydrogen bonds, and an RMSD ≤ 2.0 Å. The binding capabilities of the PFAS to the placental transporters were then evaluated based on these optimal docking results. Results The PFAS could bind to the placental transporters, with structural specificity. For example, the binding capabilities increased as the carbon chain length of PFAS increased, and it was also higher for PFOS alternatives than for PFOS. Besides, the binding capabilities of sulfonic PFAS with the same carbon chain length was also stronger than that of carboxylic PFAS. For example, the binding capabilities of PFOS (C8) to 15 placental transporters was higher than that of PFOA (C8), except for glucose transporter 1 (PFOS vs. PFOA: −4.14 vs. −4.14). Further, PFAS might be bound to the placental transporter through hydrogen, ionic, and hydrophobic interactions. Conclusion PFAS are able to bind the placental transporters, and its toxicity and exposure risk can’t be ignored.

Objective To explore the correlation of nerve function and prognosis with serum uric acid(UA),homocysteine(Hcy)and low-density lipoprotein cholesterol(LDL-C)in patients with acute cerebral infarction(ACI)after alteplase intravenous thrombolysis.Methods A total of 220 ACI patients undergoing thrombolysis in Changsha First Hospital ICU between January 2020 and December 2022 were enrolled,and according to mRS score at 3 months after thrombolysis,they were divided into poor prognosis group(mRS score＞2,91 cases)and good prognosis group(mRS score ≤2,129 cases).The serum levels of UA,Hcy and LDL-C were compared between the two groups.The correlation between the three indexes and score of National Institutes of Health Stroke Scale(NIHSS),and their predictive value for poor prognosis were analyzed.Results At 1 and 3 d after thrombolysis,the serum levels of UA,Hcy and LDL-C and NIHSS score were sig-nificantly decreased in both groups,and the serum levels of UA and Hcy and NIHSS score at 3 d after thrombolysis were significantly lower than those at 1 d(P＜0.05).The poor prognosis group had obviously higher serum levels of UA,Hcy and LDL-C and NIHSS score at 1 and 3 d after thrombolysis than the good prognosis group(P＜0.05,P＜0.01).Pearson correlation analysis showed that the serum levels of UA,Hcy and LDL-C were positively correlated with NIHSS score at 1 and 3 d after thrombolysis(P＜0.01).ROC curve analysis indicated that the AUC values of UA,Hcy and LDL-C at 1 d after thrombolysis for predicting poor prognosis were 0.707(95％CI:0.639-0.776),0.800(95％CI:0.739-0.860)and 0.624(95％CI:0.550-0.698),respectively,while the values of them at 3 d after thrombolysis were 0.655(95％CI:0.583-0.726),0.730(95％CI:0.664-0.795)and 0.573(95％CI:0.497-0.649),respectively.Conclusion In ACI patients after thrombolysis,the serum levels of UA,Hcy and LDL-C are increased in those with poor prognosis,and are associated with the severity of nerve injury.The levels at 1 d after throm-bolysis have good predictive value for poor prognosis.

Objective To analyze the detection efficiency of p16INK4a protein combined with human papillomavirus and liquid-based cytology(LCT)in the screening of cervical precancerous lesions,and to provide a basis for cervical cancer preven-tion and treatment.Methods The results of p16INK4a staining of cervical epithelial cells,human papillomavirus testing and cer-vical cytology were analyzed in 139 inpatients at Guangzhou Women's and Children's Medical Center between January 2019 and December 2020.Of them,there were 111 patients with cervical intraepithelial neoplasia(CIN)and 28 cases of cervical inflam-matory disease.The efficacy of the three methods alone and in combination to screen for CIN lesions was compared.Results In the detection of CIN patients,the sensitivity of p16INK4a,microfluidic microarray and cervical cytology for detecting CIN and a-bove lesions was 91.89% ,94.59% and82.88% ,with specificity of 57.14% ,17.86% and46.43% ,and AUC of 0.75,0.56 and 0.65,respectively;while the sensitivity of"p16INK4a+LCT","p16INK4a+hrHPV","LCT+hrHPV"and their sen-sitivity were 96.40% ,97.30% ,94.59% and 99.10% ,their specificity was 85.71% ,92.86% ,89.29% and 92.86% ,and the AUC was 0.91,0.95,0.92 and 0.96,respectively.Conclusion The combined p16INK4a and hrHPV test helps to improve diagnostic accuracy and early detection,thus allowing for earlier intervention or treatment.This combined application allows for more accurate identification of low-grade and high-grade cervical intraepithelial neoplasia,providing more information for indi-vidualized patient management.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

AIM:To investigate the mechanism through which esculetin induces ferroptosis of mouse breast cancer 4T1 cells.METHODS:Molecular docking of esculetin with p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)proteins was performed,and Kaplan-Meier curves and time-dependent receiver oper-ating characteristic curves were drawn.The 4T1 cells were divided into 6 groups,namely the control(CON),1/2 IC50,IC50,2 IC50,erastin,and capecitabine groups.The appropriate drug concentration for treating 4T1 cells was screened by CCK-8 assay.The invasion and migration abilities of 4T1 cells following esculetin treatment at the selected drug concentra-tion were analyzed by scratch test and Transwell assay.Mitochondrial morphological change were examined by electron mi-croscopy.The levels of ferroptotic cell death were then quantified by Fe2+,reactive oxygen species(ROS),malondialde-hyde(MDA),glutathione(GSH),and GPX4 assays.Western blot was performed to evaluate the protein levels of p53,SLC7A11,GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4).RESULTS:Compared with CON group,the esculetin 1/2 IC50,IC50 and 2 IC50 groups showed smaller size,increased membrane density,and decreased ridge of mitochodria,as well as decreased levels of GSH and GPX4,reduced cell invasion and migration abilities,and de-creased levels of SLC7A11 and GPX4 proteins(P＜0.05).Furthermore,these groups exhibited increased levels of Fe2+,ROS,and MDA,as well as elevated p53 and ACSL4 protein abundance(P＜0.05).CONCLUSION:Esculetin pro-motes ferroptosis of 4T1 cells through a mechanism involving the p53/SLC7A11/GPX4 regulatory axis.

In recent years,researchers have shown widespread attention in the impact of commonly used clinical anesthetics on overall physiological health by influencing mitochondrial quality.These widely used anesthetics can alter mitochondrial characteristics in several ways,such as modifying mitochondrial morphology and dynamics,affecting mitochondrial function and metabolism,and altering the expression of mitochondrial proteins.These changes have a direct or indirect effect on clinical outcomes during the peri-operative period.Either beneficial or detrimental consequences are decided by multiple factors,such as the type and dosage of anesthetic used,the timing of administration,and the patient's condition.This review comprehensively presents the effects of different types of anesthetic drugs,including intravenous anesthetics,inhalational anesthetics,analgesic,and local anesthetics,on the mitochondria quality of tissue cells and their potential mechanisms,which can facilitate selecting safer anesthesia protocols,minimizing postoperative complications,optimizing patients'postoperative recovery,developing new therapeutic strategies,and opti-mizing perioperative management.

OBJECTIVE To study the efficacy and mechanism of Shugan Jianpi Jiedu decoction in the treatment of the precancerous lesions of breast cancer through animal experiment. METHODS SD rats were taken and divided into 6 groups(10 rats in each group), namely blank group, breast precancerous lesion model group, tamoxifen group, Shugan Jianpi Jiedu decoction groups with low dose, middle dose, and high dose. DMBA modeling method was used to carry out modeling for breast precancerous lesion. HE staining was used to observe the pathological changes of breast tissue. CD4+, CD8+ were detected by flow cytometry. ELISA was used to detect IL-2, IL-4, IL-6, IL-10, IL-12, E2, P. The protein expression of ER, PI3K, p-Akt and mTOR was detected by Western blotting. RESULTS HE staining showed changes in rat mammary tissue, indicating successful modeling. Compared with the blank group, the content of CD4+ decreased and the content of CD8+ increased in the model group(P<0.01); compared with model group, the content of CD4+ increased and the content of CD8+ decreased in low, middle, high dose groups of Shugan Jianpi Jiedu decoction and tamoxifen group(P<0.01). The levels of IL-2, IL-4 and IL-10 in the model group were significantly lower than those in the blank group(P<0.01), while IL-12 and IL-6 were significantly increased(P<0.01). Compared with the model group, the concentrations of IL-2, IL-4 and IL-10 in the low, middle and high dose groups of Shugan Jianpi Jiedu decoction and the tamoxifen group were significantly increased(P<0.01), while IL-12 and IL-6 decreased significantly(P<0.05 or P<0.01). Compared with the blank group, the contents of E2 and P in the model group increased significantly(P<0.05 or P<0.01), the contents of E2 and P in the low, middle and high dose groups of Shugan Jianpi Jiedu decoction and the tamoxifen group were significantly lower than those in the model group(P<0.01). The Western blotting results showed that compared with the blank group, the expression of ER, PI3K, p-Akt and mTOR in the model group was significantly increased(P<0.01). Compared with the model group, the expression of ER, PI3K, p-Akt and mTOR in the low, medium and high dose groups of Shugan Jianpi Jiedu decoction and the tamoxifen group were significantly decreased(P<0.01). CONCLUSION Shugan Jianpi Jiedu decoction may inhibit the expression of ER, thus inhibiting the expression of PI3K/Akt/mTOR signaling pathway. Meanwhile, it can affect the immune response and reverse the precancerous lesions of breast cancer.

Objective:To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome,and to lay the foundation for the development of anti-Staphylococcus aureus drugs.Methods:The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information(NCBI)Database with Staphylococcus aureus as the keyword;BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus;subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes.These potential antibacterial targets were used as the receptors;LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration(FDA)-approved drug library;molecular docking technology was used to analyze the binding abilities of the drugs and targets.Results:There were 14 379 gene families in the 50 Staphylococcus aureus genomes,of which 1 620 were the core genes.The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target.LibDock software screened out nine compounds,including balofloxacin,tenofovir disoproxil fumarate,and adefovir,that may exert anti-Staphylococcus aureus effects on this target protein.The molecular docking results showed there was good binding abilities between the targets and the compounds.Conclusion:Tyrosine autokinase may be the potential target for antii-Staphylococcus aureus.

Objective To prepare FLIVIGSII peptide(FI peptide)and investigate its physicochemical properties and hemostatic effect in vivo and in vitro.Methods The self-assembling peptide-based hydrogels were prepared by the FI peptide mixed with water.After gross observation for the hydrogel state of the FI peptide,scanning electron microscopy(SEM)and transmission electron microscopy(TEM)were used for its microstructure,and dynamic light scattering(DLS)was performed for its size.The hemostatic effect of FI peptide after being mixed with blood samples treated with 3.8％sodium citrate was observed,and the microstructure of the blood clot was observed with SEM.CCK-8 assay and hemolysis assay were performed to verify its biocompatibility.After a rat model of hepatic parenchymal perforation and hemorrhage was established,15 female SD rats(6～8 weeks old,weighing 150 g)were randomly divided into control group,FI peptide group and fibrin sealant group.The hemostatic effect of FI peptide and prognosis was observed and analyzed after treatment in each group,and the hemostatic mechanism was also investigated.Results FI peptides were successfully prepared,and it could rapidly self-assemble into a nanofiber network hydrogel in water,and further cause formation of blood clots.SEM showed that FI peptides self-assembled to form fibrous hydrogels after mixing with water.TEM results verified that the FI peptide formed into nanofibers in a diameter of 13.70±2.31 nm after gelatinization in water,and DLS results verified that the FI peptide formed polydisperse and multi-size nanofibers in water(in a range of 148.2～208.0 nm or 575.0～807.0 nm).The fibrous hydrogel formed by the FI peptide mixed with the blood could envelop the red blood cells,thus form a physical hemostatic barrier to achieve blood clotting in seconds.FI peptide hydrogel had no cytotoxicity to normal hepatocytes(L-O2 cells)and did not cause hemolysis of red blood cells.In in vivo experiment,FI peptide quickly formed nanofiber hydrogel when in contact with blood,thus formed physical hemostasis barrier to achieve hemostasis within a few seconds(hemostasis time＜5 s).Conclusion The FI peptide exhibits a rapid and efficient hemostatic effect,indicating a promising clinical application in the hemostasia of hepatic parenchymal traumatic hemorrhage.