ObjectiveAbnormal lipids in neurons can cause the accumulation of α-synuclein（α-syn）. This study aimed to explore the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） mice using lipidomics combined with network pharmacology. MethodsMice were divided into the blank group， model group and ASH （45.5 mg·kg^-1） group. Motor ability was evaluated by pole climbing time and autonomous activity count； The oxidative stress indicators were detected by enzyme-linked immunosorbent assay （ELISA）. Lipid biomarkers in brain tissues were screened and identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and metabolic pathway analysis was conducted. The key targets of ASH for PD treatment were explored using network pharmacology. The Kyoto Encyclopedia of Genes and Genomes （KEGG） database was used for pathway enrichment analysis， and the "compound-reaction-enzyme-gene" network was constructed using the MetScape plugin. The protein expression levels of glutathione S-transferase P1 （GSTP1）， glutathione S-transferase Mu 2 （GSTM2）， prostaglandin peroxide synthase 1 （PTGS1）， prostaglandin peroxide synthase 2 （PTGS2）， and prostaglandin E synthase （PTGES） were validated by Western blot. ResultsCompared with the blank group， the model group showed significantly prolonged pole climbing time and reduced autonomous activity count （P<0.01）. Compared with the model group， the ASH group demonstrated significantly faster pole climbing and increased autonomous activity count （P<0.01）. The model group exhibited significantly decreased superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） levels， and increased malondialdehyde （MDA） level in brain tissues compared with the blank group （P<0.01）. The ASH group showed increased SOD and GSH-Px levels and decreased MDA level compared with the model group （P<0.05， P<0.01）. Lipidomics analysis identified 10 differential metabolites and 8 differential metabolic pathways. Network pharmacological analysis revealed 213 intersection targets between ASH components and PD， with KEGG enrichment involving the sphingolipid signaling pathway， lipid arteriosclerosis， phosphoinositide 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway， and hypoxia inducible factor-1（HIF-1） signaling pathway. Integrated lipidomics and network pharmacology analysis highlighted the central role of the arachidonic acid metabolic pathway. The Western blot results showed that ASH effectively up-regulated GSTP1， GSTM2， and PTGS1 protein expression， and down-regulated PTGS2 and PTGES protein expression. ConclusionASH can ameliorate behavioral deficits， exert antioxidant effects， regulate lipid differential metabolites and the arachidonic acid metabolic pathway， thereby exerting therapeutic effects in PD model mice.

ObjectiveTo analyze the long-term trend of incidence and mortality of type 2 diabetic kidney disease （DKD） in China from 1990 to 2021. MethodsThe Joinpoint regression model was used to analyze the average annual percentage change （AAPC） of standardized incidence rate and standardized mortality rate， and the age-period-cohort （APC） model was constructed to analyze the longitudinal age change， period and cohort effect risk ratio （RR）. ResultsFrom 1990 to 2021， the standardized incidence rate of type 2 DKD in males and females showed an overall upward trend， with AAPC of 0.08% and 0.36%， respectively. The age-standardized mortality rate of the total population and female showed a downward trend， with AAPC of -0.61% and -1.03%， respectively. However， there was no significant difference in males. APC model showed that the age effect existed： the peak age was 75-79 years old， the mortality rate of females increased， and the mortality rate of males decreased after 80-84 years old. For the effect of time period， the risk of type 2 DKD incidence in females in 2017—2021 was 1.05 times that in 2002—2006， and the risk of death in males and females in 2017—2021 was 0.84 and 0.71 times that in 2002—2006， respectively. For cohort effects， the highest risk of disease was seen in men and women born in 1967—1971， and the highest risk of death was seen in men born in 1952—1956 and women born in 1912—1916. ConclusionFrom 1990 to 2021， the standardized incidence rate of type 2 DKD in China shows an upward trend， and the standardized mortality rate shows a downward trend. It is necessary to strengthen the health behavior publicity and education of type 2 DKD， and actively carry out early screening to reduce the disease burden.

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by synovial inflammation, cartilage loss. Often manifesting as joint pain and limited mobility, it severely affects the quality of life of patients. Traditional treatment methods such as pharmacological injections and surgical interventions primarily aim to alleviate symptoms but have limited effects on cartilage repair. Human umbilical cord mesenchymal stem cells (hUC-MSCs), due to their anti-inflammatory and chondrogenic capabilities, is considered a new hope for the treatment of KOA. This article synthesizes the latest research findings from both domestic and international sources to discuss the theoretical basis for the clinical application of hUC-MSCs in treating KOA, clinical study design, and efficacy evaluation. It also addresses the challenges in the clinical application of hUC-MSCs and explores future directions, in the hope of providing feasible theoretical support for the treatment of KOA with hUC-MSCs.

[Objective] To explore the strategy of blood management in patients with massive transfusion in the frigid plateau region. [Methods] The treatment process of a patient with liver rupture in the frigid plateau region was analyzed, and the blood management strategy of the frigid plateau region was discussed in combination with the difficulties of blood transfusion and literature review. [Results] The preoperative complete blood count (CBC) test results of the patient were as follows: RBC 3.14×10¹²/L, Hb 10⁶ g/L, HCT 30.40%, PLT 115.00×10⁹/L; coagulation function: PT 18.9 s, FiB 1.31 g/L, DD > 6 μg/mL, FDP 25.86 μg/mL; ultrasound examination and imaging manifestations suggested liver contusion and laceration / intraparenchymal hematoma, splenic contusion and laceration, and massive blood accumulation in the abdominal cavity; it was estimated that the patient's blood loss was ≥ 2 000 mL, and massive blood transfusion was required during the operation; red blood cell components were timely transfused during the operation, and the blood component transfusion was guided according to the patient's CBC and coagulation function test results, providing strong support and guarantee for the successful treatment of the patient. The patient recovered well after the operation, and the CBC test results were as follows: RBC 4.32×10¹²/L, Hb 144 g/L, HCT 39.50%, PLT 329.00×10⁹/L; coagulation function: APTT 29.3 s, PT 12.1 s, FiB 2.728 g/L, DD>6 μg/mL, FDP 25.86 μg/mL. The patient was discharged after 20 days, and regular follow-up reexamination showed no abnormal results. [Conclusion] Individualized blood management strategy should comprehensively consider the patient’s clinical symptoms, the degree of hemoglobin decline, dynamic coagulation test results and existing treatment conditions. Efficient and reasonable patient blood management strategies can effectively improve the clinical outcomes of massive transfusion patients in the frigid plateau region.

Circulating tumor cells (CTCs) have the ability to sow tumors and can be found in the peripheral blood of patients with precancerous lesions and healthy people. However, CTCs are not currently screened in the donors blood. A large number of allogeneic blood transfusions occurred worldwide each year, and allogeneic blood transfusions expose recipients to the risk of transmission and affect tumors associated with donor CTCs. Although leukocyte filtration can not completely remove tumor cells in the blood, it can effectively reduce the number of white blood cells in the blood and reduce their proliferation ability. Blood irradiation can effectively destroy the DNA of CTCs in the blood, and inhibit the occurrence and metastasis of tumors caused by the infusion of allogeneic blood containing CTCs. Therefore, we should pay attention to the potential risk of CTCs on clinical transfusion, and strengthen the preclinical treatment of blood to avoid donor-related tumor infection in blood recipients due to clinical transfusion.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

OBJECTIVES: To investigate the mechanism by which Guijianyu ameliorates podocyte injury in a mouse model of diabetic kidney disease (DKD) induced by advanced glycation endproducts (AGEs). METHODS: Sixty db/db mouse models of DKD were randomized equally into 5 groups for treatment with saline, Guijianyu extract at 3 doses or irbesartan for 12 weeks, and the changes in renal pathology and structure were observed using transmission electron microscopy, and the expressions of related genes and key proteins were detected using RT-qPCR and immunohistochemistry. In cultured MPC-5 cells incubated with 50 mg/L AGEs-BSA for 24 h, the effect of different concentrations of Guijianyu extract on cell viability was examined with CCK-8 assay; Western blotting was performed to detect the protein expressions of RAGE, VEGFA, TNF-α, NF-κB(p65), IL-6 and caspase-3, and the mRNA expressions of RAGE, NF-κB (p65), VEGFA and IL-6 were detected with RT-qPCR. RESULTS: In mouse models of DKD, treatment with high-dose Guijianyu extract significantly reduced renal expressions of RAGE, VEGFA, NF-κB(p65), and IL-6 proteins and the mRNA expressions of RAGE, NF-κB, and IL-6. In MPC-5 cells, exposure to AGEs significantly reduced cell viability and increased the protein expressions of RAGE, NF‑κB (p65), VEGFA, TNF-α, IL-6 and caspase-3 (P<0.05) and mRNA expressions of RAGE, NF-κB (p65), VEGFA, and IL-6. Treatment with Guijianyu extract obviously improved cell viability and reduced the expressions of RAGE, NF-κB(p65), VEGFA, TNF-α, IL-6, and caspase-3. Furthermore, Guijianyu extract effectively reversed RAGE agonist-induced elevation of protein expressions of RAGE, VEGFA, TNF-α, IL-6, and caspase-3 and mRNA expressions of RAGE, NF-κB (p65), IL-6, and VEGFA in MPC-5 cells. CONCLUSIONS Guijianyu extract ameliorates AGEs-induced mouse renal podocyte injury in DKD by inhibiting the activation of AGEs-RAGE signaling pathway and reducing the expressions of pro-inflammatory cytokines and vascular endothelial growth factors.
Animals ; Glycation End Products, Advanced ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Signal Transduction/drug effects* ; Podocytes/pathology* ; Diabetic Nephropathies/drug therapy* ; Receptor for Advanced Glycation End Products ; Vascular Endothelial Growth Factor A/metabolism* ; Interleukin-6/metabolism* ; Male

Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

One of the technical bottlenecks limiting the high yield of 1,4-butanediamine is the insufficient tolerance of strains to 1,4-butanediamine. Enhancing the tolerance of strains to 1,4-butanediamine is therefore a primary challenge that needs to be addressed for the construction of strains with high yields of 1,4-butanediamine. Staphylococcus pasteuri 326180 exhibits exceptional tolerance to high-concentration 1,4-butanediamine, serving as both an ideal model for studying the mechanism underlying the 1,4-butanediamine tolerance and a novel host for constructing strains capable of efficiently producing 1,4-butanediamine. However, for both the research on the tolerance mechanism and the modification of chassis strains, gene editing of S. pasteuri needs to be carried out at the molecular level. The research objective of this paper is to establish a genetic manipulation system for S. pasteuri, laying foundation for subsequent studies on tolerance mechanism and the modification of chassis strains. This study systematically optimized the electroporation conditions, including key parameters such as the growth phase of cells, electric field strength, electroporation buffer, and recovery medium, successfully establishing an electroporation method for S. pasteuri. Additionally, we constructed the gene editing plasmid pCpfOA by replacing the resistance expression cassette, optimized the selection markers for gene editing, and finally established a CRISPR/Cpf1-based gene editing technology for S. pasteuri, achieving an editing efficiency of 90%. The genetic manipulation system of S. pasteuri established in this study provides technical support for research into the tolerance mechanism of this bacterium and the genetic modification of chassis strains.
Staphylococcus/drug effects* ; Gene Editing/methods* ; Electroporation/methods* ; Plasmids/genetics* ; CRISPR-Cas Systems ; Genetic Engineering/methods*

Objective To investigate the relationship between the expression of serum microRNA(miR)-488 and miR-184 and the occurrence of preeclampsia in patients with gestational hypertension.Methods A to-tal of 128 patients with gestational hypertension admitted to a hospital from June 2022 to March 2023 were se-lected and divided into the simple gestational hypertension group(55 cases)and the combined with pre-eclampsia group(73 cases)according to whether they developed preeclampsia.Another 46 healthy pregnant women in the same period were selected as the control group.Real-time fluorescence quantitative polymerase chain reaction was used to detect miR-488 and miR-184 expression in each group,and multiple Logistic regres-sion was used to analyze the influencing factors of the occurrence of preeclampsia in patients with gestational hypertension.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of each influencing factor in the occurrence of preeclampsia in patients with gestational hypertension,and Pearson cor-relation was used to analyze the correlation between serum miR-488,miR-184 and placental growth factor.Re-sults Compared with the control group,the expressions of serum miR-488 and miR-184 were increased in the simple pregnancy hypertension group and the combined with preeclampsia group,and the differences were sta-tistically significant(P<0.05).Compared with mild preeclampsia group,serum miR-488 and miR-184 ex-pressions were increased in severe preeclampsia group,and the difference was statistically significant(P<0.05).There were significant differences in gravida and parity,systolic blood pressure,diastolic blood pres-sure,urinary protein quantity and placental growth factor levels between the combined with preeclampsia group and the simple pregnancy hypertension group(P<0.05).Multiple Logistic regression analysis showed that gravida and parity,systolic blood pressure,diastolic blood pressure,urinary protein quantity,miR-488 and miR-184 were risk factors for preeclampsia in patients with gestational hypertension(P<0.05),and placental growth factor was protective factor for preeclampsia in patients with gestational hypertension(P<0.05).ROC curve analysis showed that the prediction efficiency of miR-488+miR-184 was significantly better than that of serum miR-488(Z=2.530,P=0.011)and miR-184(Z=2.437,P=0.015)alone.Serum miR-488 and miR-184 were negatively correlated with placental growth factor(r=-4.361,-4.288,P<0.05).Con-clusion Serum miR-488 and miR-184 have predictive value in the occurrence of preeclampsia in patients with gestational hypertension.