ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

Objective: To analyze the epidemiological characteristics and spatial-temporal clustering characteristics of pulmonary tuberculosis in Huangpu District, Shanghai Municipality from 2009 to 2023, so as to provide the evidence for formulating targeted pulmonary tuberculosis prevention and control strategies. Methods: Data of registered pulmonary tuberculosis cases in Huangpu District from 2009 to 2023, including gender, age, occupation, and pathogenetic test results, were collected from the Tuberculosis Management Information System of the China Disease Prevention and Control Information System. The registered incidence was calculated, and the trend was analyzed using the annual percent change (APC) and average annual percent change (AAPC). Spatial distribution pattern was analyzed using kernel density estimation and the average nearest neighbor methods. The temporal-spatial clustering characteristics of pulmonary tuberculosis were identified using the spatio-temporal scan analysis. Results: A total of 2 726 pulmonary tuberculosis cases were registered in Huangpu District from 2009 to 2023. The registered incidence decreased from 31.20/100 000 in 2009 to 15.06/100 000 in 2023 (AAPC=-6.156%, P<0.05). A sharp declining trend was particularly observed from 2017 to 2023 (APC=-11.355%, P<0.05). Among them, 1 239 were pathogen-positive, and the pathogen positivity rate increased from 40.80% in 2009 to 71.05% in 2023 (P<0.05). There were 1 906 male cases and 820 female cases, with a male-to-female ratio of 2.32∶1. There were 798 cases aged 45-<60 years and 981 retirees, accounting for 29.27% and 35.99%, respectively. Temporal-spatial clustering analysis revealed spatial clustering areas during both 2009-2016 and 2017-2023 (both P<0.05). The clustering area for 2009-2016 was located in the central-eastern part of Huangpu District, with the clustering time in 2012. The clustering area for 2017-2023 was in the southwestern part, with the clustering time in 2017. Conclusions The registered incidence of pulmonary tuberculosis in Huangpu District showed a downward trend from 2009 to 2023. The spatial clustering areas were identified in the central-eastern part in Huangpu District in 2012 and the southwestern part in 2017.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

Phosgene is a highly reactive chemical substance and a prevalent chemical warfare agent,and it is vitally important for rapid and accurate detection of phosgene to counteract terrorist threats and industrial accidents.In this work,a phosgene probe,designated as SX-Pho,which incorporated benzimidazole and hydroxyl groups as recognition motifs,was prepared through Suzuki coupling and Debus-Radziszewski methodologies to incorporate an electron-donating carbazole moiety.This probe exhibited a large Stokes shift(Approximately 130 nm).Upon exposure to triphosgene/triethylamine conditions(in situ phosgene generation),the fluorescence emission of probe at 470 nm underwent significant quenching,with a 20-fold reduction in intensity,while the fluorescence lifetime decreased from 3.30 ns to 3.06 ns.Concentration titration experiments demonstrated that SX-Pho achieved a lower detection limit of 57.8 nmol/L with high specificity and interference resistance.Preton nuclear magnetic resonance spectroscopy(1H NMR),high-resolution mass spectrometry,and density functional theory(DFT)calculations confirmed the cyclization reaction between hydroxyl groups,imines,and phosgene.The extent of overlap between the highest occupied molecular orbital(HOMO)and the lowest unoccupied molecular orbital(LUMO)was notably decreased,leading to the suppression of radiative transitions.The energy gap underwent a reduction of 0.43 eV,while the non-radiative transition was augmented,resulting in fluorescence quenching and achieving rapid detection of phosgene.Based on this,probe-loaded test strips were prepared.The color change under 365 nm illumination allowed visual discrimination of phosgene at concentrations below 20 μL/L.Furthermore,using a smartphone's built-in RGB application to measure the intensity of the blue(B)channel after the test strips were exposed to phosgene enabled both qualitative and quantitative detection.The detection range was 1.82-50 μL/L,with a limit of detection(LOD)of 1.814 μL/L.

Objective:To assess the impact of different exercise modalities on cognitive and physical functions in elderly patients with cognitive frailty using a network meta-analysis based on frequency theory.Methods:A comprehensive computer and manual search was conducted in PubMed, Web of Science, Embase, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for randomized controlled trials on the effects of exercise training on cognitive and physical functions in elderly patients with cognitive frailty. The search covered studies published until December 31, 2023. To ensure the rigor of the study, two researchers independently screened the literature, evaluated the quality using the Cochrane risk of bias tool, and extracted data. Statistical analysis was conducted using Stata 14.0 software.Results:A total of 16 studies were included, involving 10 different exercise interventions (Baduanjin, Tai Chi Chuan, Mindfulness-based Tai Chi Chuan, Otago exercise, high-intensity interval training, dual-task exercise training, multicomponent exercise, aerobic exercise, resistance exercise, and combined aerobic and resistance exercise). The network meta-analysis results showed that, compared with non-exercise control groups, Baduanjin and dual-task exercise training improved cognitive function in elderly patients with cognitive frailty ( P<0.05), with Baduanjin showing the best effect ( SUCRA=0.79). Multicomponent exercise improved frailty ( P<0.05) with the best effect ( SUCRA=1.00), it also improved grip strength ( P<0.05), with the best effect ( SUCRA=0.89). Multicomponent exercise and dual-task exercise training improved walking speed ( P<0.05), multicomponent exercise had the best effect ( SUCRA=1.00) . Conclusions:Baduanjin has an advantage in improving cognitive function in elderly patients with cognitive frailty, while multicomponent exercise is more effective in improving frailty, grip strength, and walking speed. However, the conclusions of this study need further validation.

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

This study aims to investigate the action mechanism of Shenzhuo Decoction(SZT, i.e., Ganjiang Lingzhu Decoction) in treating knee osteoarthritis(KOA). Network pharmacology was used to analyze the key targets of SZT in the treatment of KOA. At the cellular experimental level, primary chondrocytes extracted from rats were used for in vitro validation. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) staining was employed to detect chondrocyte apoptosis in the knee joint. Western blot was performed to analyze the expression of the anti-apoptotic factor(Bcl2), the apoptosis marker gene Bax, and key proteins in the phosphoinositide 3-kinase(PI3K)-protein kinase B(Akt) signaling pathway. In animal experiments, 60 7-week-old male SD rats were used to establish a KOA model and randomly divided into a control group, a KOA model group, high-, medium-, and low-dose SZT groups, and a celecoxib group, with 10 rats in each group. Micro-CT was used to observe changes in bone mineral density and osteophytes at the articular cartilage surface. Hematoxylin-eosin(HE) staining and safranin O-fast green(SFO) staining were used to observe pathological changes in cartilage tissue. Immunohistochemistry was used to detect the expression of inflammatory factor matrix metalloproteinase 13(MMP13) and cartilage marker collagen Ⅱ. Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to detect the expression of chondrocyte marker SRY-box transcription factor 9(SOX9) and inflammatory markers matrix metalloproteinase 9(MMP9), interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Cell experiments revealed that SZT effectively improved KOA, and the results of micro-CT and HE and SFO staining showed that compared with the control group, the model group had obvious formation of osteophytes on the joint surface, which became rough, with significant decreases in the trabecular bone volume fraction(BV/TV), trabecular number(Tb.N), and trabecular thickness(Tb.Th) and a significant increase in trabecular spacing(Tb.Sp). The SZT groups had few osteophytes and a smoother joint surface than the model group. Additionally, BV/TV, Tb.N, and Tb.Th were significantly increased, while Tb.Sp was gradually decreased. A SZT-component-KOA target network was constructed to locate the core targets in KOA treatment, which was further validated through in vivo and in vitro animal experiments. The immunohistochemistry results of the pathological section of rat joint tissue showed that compared with the control group, the model group had a significant increase in MMP13 and a decrease in collagen Ⅱ, while SZT could inhibit inflammation and strengthen the protection of collagen Ⅱ in articular cartilage. The qRT-PCR results showed that SZT could significantly inhibit the mRNA expression of IL-6, IL-1β, TNF-α, and MMP9 and upregulate the mRNA level of SOX9. The TUNEL detection results showed that in the lipopolysaccharide(LPS)-induced KOA model group, chondrocyte apoptosis was significantly increased, and the fluorescence intensity was significantly enhanced. SZT, however, significantly reduced the trend of chondrocyte apoptosis and decreased the fluorescence intensity. The Western blot results showed that SZT could effectively inhibit the phosphorylation level of proteins in the PI3K-Akt pathway, reduce the expression of Bax, increase the expression of Bcl2, and inhibit the degradation of SOX9. In conclusion, SZT may alleviate the degenerative damage of KOA by inhibiting the phosphorylated expression of key proteins in the PI3K-Akt signaling pathway, reducing the release of inflammatory factors, and inhibiting chondrocyte apoptosis.
Animals ; Chondrocytes/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Osteoarthritis, Knee/physiopathology* ; Rats, Sprague-Dawley ; Rats ; Apoptosis/drug effects* ; Signal Transduction/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Humans

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans