The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1^OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1^OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans ; Arthritis, Rheumatoid/genetics* ; Macrophages/immunology* ; Fibroblasts/metabolism* ; Phenotype ; Extracellular Matrix Proteins/genetics* ; Proteoglycans/genetics* ; Synovial Membrane/cytology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; Nitric Oxide Synthase Type II/genetics* ; Cell Differentiation ; Coculture Techniques ; THP-1 Cells

This study analyzed the clinical and laboratory data of 3 children diagnosed with mitochondrial disease-associated primary adrenal insufficiency (PAI) at the Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from October 2018 to November 2023.All patients were normal at birth but gradually developed symptoms and were diagnosed with PAI between the ages of 1 year and 1 month and 7 years and 3 months.The children presented typical clinical symptoms of PAI, including skin and mucosal hyperpigmentation (3 cases), electrolyte disturbances (3 cases), and hypoglycemia (2 cases), as well as multisystem abnormalities related to mitochondrial disease, including recurrent infections, growth retardation, cachexia, and hyperlactatemia.Genetic testing revealed significant single deletions in mitochondrial DNA in all patients: Patient 1: m.11219_15954del, Patient 2: m.8483_13459del, and Patient 3: m.8649_16084del.Treatment with Hydrocortisone acetate replacement therapy improved the electrolyte disturbances and hypoglycemia, but issues with recurrent infections, growth retardation, and cachexia persisted.This study suggests that in clinical practice, the possibility of mitochondrial disease should be highly suspected when PAI patients present with multisystem abnormalities, especially in conjunction with hyperlactatemia.

Objective:To explore the impact of residents′ health literacy on healthcare choices.Methods:This mixed cross-sectional study utilized data from the 2009, 2011, and 2015 waves of the China Health and Nutrition Survey (CHNS), including adults aged≥18 years. Guided by Andersen′s Behavioral Model of Health Services Use and the Knowledge-Attitude-Practice (KAP) framework, variables were collected across three dimensions-predisposing, enabling, and need factors-including gender, marital status, age, education level, employment status, urban/rural residence, health management awareness, income, health insurance coverage, self-rated health, and chronic disease status. A multinomial Logistic regression model was applied to assess the association between health literacy and healthcare choice. Bootstrap analysis was conducted to test the mediating effect of health management awareness.Results:After excluding cases with missing or invalid data, 4 736 valid observations were included. The proportions of choosing township-, county-, and city-level hospitals were 60.60%, 15.08%, and 24.32%, respectively. After adjusting for confounders, health literacy showed a significant effect on healthcare choice ( P<0.05): individuals with higher health literacy were more likely to choose county-level hospitals ( RR=1.035, P<0.05) and city-level hospitals ( RR=1.044, P<0.01). Health management awareness mediated the relationship between health literacy and healthcare choice ( P<0.05). Conclusions:Health literacy significantly influences healthcare choices; individuals with higher health literacy are more inclined to utilize higher-level medical institutions. Furthermore, health literacy affects healthcare choices partly through the mediating role of health management awareness.

Objective:To explore the impact of residents′ health literacy on healthcare choices.Methods:This mixed cross-sectional study utilized data from the 2009, 2011, and 2015 waves of the China Health and Nutrition Survey (CHNS), including adults aged≥18 years. Guided by Andersen′s Behavioral Model of Health Services Use and the Knowledge-Attitude-Practice (KAP) framework, variables were collected across three dimensions-predisposing, enabling, and need factors-including gender, marital status, age, education level, employment status, urban/rural residence, health management awareness, income, health insurance coverage, self-rated health, and chronic disease status. A multinomial Logistic regression model was applied to assess the association between health literacy and healthcare choice. Bootstrap analysis was conducted to test the mediating effect of health management awareness.Results:After excluding cases with missing or invalid data, 4 736 valid observations were included. The proportions of choosing township-, county-, and city-level hospitals were 60.60%, 15.08%, and 24.32%, respectively. After adjusting for confounders, health literacy showed a significant effect on healthcare choice ( P<0.05): individuals with higher health literacy were more likely to choose county-level hospitals ( RR=1.035, P<0.05) and city-level hospitals ( RR=1.044, P<0.01). Health management awareness mediated the relationship between health literacy and healthcare choice ( P<0.05). Conclusions:Health literacy significantly influences healthcare choices; individuals with higher health literacy are more inclined to utilize higher-level medical institutions. Furthermore, health literacy affects healthcare choices partly through the mediating role of health management awareness.

This study analyzed the clinical and laboratory data of 3 children diagnosed with mitochondrial disease-associated primary adrenal insufficiency (PAI) at the Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from October 2018 to November 2023.All patients were normal at birth but gradually developed symptoms and were diagnosed with PAI between the ages of 1 year and 1 month and 7 years and 3 months.The children presented typical clinical symptoms of PAI, including skin and mucosal hyperpigmentation (3 cases), electrolyte disturbances (3 cases), and hypoglycemia (2 cases), as well as multisystem abnormalities related to mitochondrial disease, including recurrent infections, growth retardation, cachexia, and hyperlactatemia.Genetic testing revealed significant single deletions in mitochondrial DNA in all patients: Patient 1: m.11219_15954del, Patient 2: m.8483_13459del, and Patient 3: m.8649_16084del.Treatment with Hydrocortisone acetate replacement therapy improved the electrolyte disturbances and hypoglycemia, but issues with recurrent infections, growth retardation, and cachexia persisted.This study suggests that in clinical practice, the possibility of mitochondrial disease should be highly suspected when PAI patients present with multisystem abnormalities, especially in conjunction with hyperlactatemia.

Objective To investigate the effects of Nel-like type 1 molecule(NELL-1)on the proliferation and osteogenic differenti-ation of stem cells from human exfoliated deciduous teeth(SHEDs).Methods SHEDs was isolated,cultured,and identified.The third generation SHEDs were used for subsequent experiments.SHEDs were divided into 4 groups,and NELL-1 was added to each group at concentrations of 0(control group),50,100,and 200 ng/mL.Cell activity was measured by CCK-8 assay and crystal violet staining.The changes in osteogenic ability were detected by alkaline phosphatase activity.The expression levels of osteogenesis-related genes ALP,OCN and Runx-2 by RT-qPCR were detected.Western blot was used to detect the expression of osteogenesis-related pro-teins ALP,Runx-2 and Col-Ⅰ.Results SHEDs exhibited stem cell characteristics,and 50 ng/mL of NELL-1 protein had a promo-ting effect on SHEDs proliferation(P＜0.01).Alkaline phosphatase activity assay showed that after the addition of NELL-1,the osteo-genic effect of each group was better than that of the control group and 50 ng/mL of NELL-1 was the best(P＜0.05).RT-qPCR and Western blot results showed that 50 ng/mL of NELL-1 significantly promoted the expression of osteoblast-related genes including ALP,OCN and Runx-2 and the protein expression of ALP,Runx-2 and Col-Ⅰ(P＜0.05).Conclusion NELL-1 can promote the prolifera-tion and osteogenic differentiation of SHEDs.

Objective To compare the consistency of voice parameters collected by commonly used smart-phone brands in China and professional recording equipment,and to study whether smartphones can be used for voice research.Methods A total of 67 normal subjects were selected for voice recording using six different smart-phone brands(via the"Active Health"screening APP from the National Key Research and Development Program)and professional recording equipment.Acoustic voice parameters such as fundamental frequency parameters,fre-quency variation parameters,amplitude variation parameters,formant parameters,and energy parameters were ex-tracted from the vowels/a/,/i/,and/u/.A one-way ANOVA test and Tukey's HSD post-hoc comparisons were conducted on the independent variables.Results There were no significant differences between smartphones and professional recording equipment in terms of fundamental frequency parameters such as median F0,mean F0,max F0 and min F0;frequency parameters such as jitter local,jitter local absolute,jitter rap,jitter ppq5,and jitter ddp;amplitude parameters such as shimmer local,shimmer local dB,shimmer apq3,shimmer apq5,shimmer apq11,and shimmer dda;and formant parameters such as F1,F2,F3,and F4.However,significant differences were found in energy parameters such as mean energy(F=31.171,P＜0.001),max energy(F=34.193,P＜0.001),and min energy(F=5.453,P＜0.001)between smartphones and professional recording equipment.Conclusion The smartphones using the"Active Health"screening app from the National Key Research and Development Program can replace professional recording equipment for voice research.However,caution should be exercised when selec-ting energy-related acoustic parameters.

Objective To analyze the risk factors and effective predictive indicators for postpartum hemor-rhage(PPH)in pregnant women with severe pre-eclampsia(sPE)in singleton pregnancies.The findings will serve as a valuable reference for the clinical prevention and management of PPH in these patients.Methods A retrospective analysis was conducted on 932 pregnant women with sPE at two tertiary hospitals in Guangzhou from January 1,2016,to December 31,2022.Among these,95 cases were complicated by PPH.A comparative analysis was performed between the sPE group and the sPE with PPH group.Results(1)The incidence of assisted reproductive technology,intrapartum blood loss,placental abruption,elevated D-dimer levels,increased monocyte counts,and higher SIRI levels were significantly higher in the PPH group,whereas platelet counts were significantly lower(P<0.05).(2)The results indicated that intrapartum blood loss,D-dimer levels,and platelet counts were inde-pendently associated with PPH in pregnant women with sPE.(3)The area under the curve(AUC)for intrapartum blood loss,D-dimer,and platelet counts were 0.805,0.717,and 0.571,respectively.The optimal cutoff value for D-dimer was determined to be 2.295 μg/mL.The combined AUC for intrapartum blood loss and D-dimer was 0.859.(4)Intrapartum blood loss values were significantly higher in the PPH group for both vaginal delivery and cesarean section(P<0.001).The corresponding optimal cutoff values were 285 mL and 375 mL,respectively.Conclusions Intrapartum haemorrhage,D-dimer levels,and platelet count were identified as independent risk factors for PPH in pregnant women with sPE.Specifically,pregnant women with sPE who experienced blood loss exceeding 285 mL during vaginal delivery or 375 mL during caesarean section,along with a D-dimer level greater than 2.295 μg/mL,demonstrated an increased likelihood of developing PPH.Therefore,it is crucial to enhance clinical monitoring of these relevant indicators in high-risk populations.