N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer.

BACKGROUND: N6-methyladenosine (m6A) methylation modification exists in Epstein-Barr virus (EBV) primary infection, latency, and lytic reactivation. It also modifies EBV latent genes and lytic genes. EBV-associated gastric cancer (EBVaGC) is a distinctive molecular subtype of GC. We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC. AIM: To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC. METHODS: First, The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC (EBVnGC). Second, we identified Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of m6A-related differentially expressed genes. We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment (TME). Finally, cell counting kit-8 cell proliferation test, transwell test, and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1 (IGFBP1) in EBVaGC cell lines. RESULTS: m6A methylation regulators were involved in the occurrence and development of EBVaGC. Compared with EBVnGC, the expression levels of m6A methylation regulators Wilms tumor 1-associated protein, RNA binding motif protein 15B, CBL proto-oncogene like 1, leucine rich pentatricopeptide repeat containing, heterogeneous nuclear ribonucleoprotein A2B1, IGFBP1, and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC (P < 0.05). The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher (P = 0.046). GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC. Compared with EBVnGC, the infiltration of activated CD4+ T cells, activated CD8+ T cells, monocytes, activated dendritic cells, and plasmacytoid dendritic cells were significantly upregulated in EBVaGC (P < 0.001). In EBVaGC, the expression level of proinflammatory factors interleukin (IL)-17, IL-21, and interferon-γ and immunosuppressive factor IL-10 were significantly increased (P < 0.05). In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line (SNU719) than in an EBVnGC cell line (AGS) (P < 0.05). IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719. Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS. CONCLUSION: m6A regulators could remodel the TME of EBVaGC, which is classified as an immune-inflamed phenotype and referred to as a "hot" tumor. Among these regulators, we demonstrated that IGFBP1 affected proliferation, migration, and apoptosis.

Beneficial effects of Dendrobium officinale National Herbal Drink on metabolic immune crosstalk via regulate SCFAs-Th17/Treg.

BACKGROUND: The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied. OBJECTIVES: The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake. METHODS: In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 ml/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16S rRNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk. RESULTS: Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured_bacterium_g__norank_f__muribaculacea and uncultured_bacterium_g__Turicibacter. Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4+T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder. CONCLUSIONS: Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4+T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis.

Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial.

BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.

Transcriptome analysis of Vero cells infected with attenuated vaccine strain CDV-QN-1.

To better understand the interaction between attenuated vaccines and host antiviral responses, we used bioinformatics and public transcriptomics data to analyze the immune response mechanisms of host cells after canine distemper virus (CDV) infection in Vero cells and screened for potential key effector factors. In this study, CDV-QN-1 infect with Vero cells at an MOI of 0.5, and total RNA was extracted from the cells 24 h later and reverse transcribed into cDNA. Transcriptome high-throughput sequencing perform using Illumina. The results showed that 438 differentially expressed genes were screened, of which 409 were significantly up-regulated and 29 were significantly down-regulated. Eight differentially expressed genes were randomly selected for RT-qPCR validation, and the change trend was consistent with the transcriptomics data. GO and KEGG analysis of differentially expressed genes revealed that most of the differentially expressed genes in CDV-QN-1 infection in the early stage were related to immune response and antiviral activity. The enriched signaling pathways mainly included the interaction between cytokines and cytokine receptors, the NF-kappa B signaling pathway, the Toll-like receptor signaling pathway, and the NOD-like receptor signaling pathway. This study provides a foundation for further exploring the pathogenesis of CDV and the innate immune response of host cells in the early stage of infection.

Effects of socioeconomic status and regional inequality on the association between PM2.5 and its components and cardiometabolic multimorbidity: A multicenter population-based survey in eastern China.

BACKGROUND: Despite evidence linking fine particulate matter (PM2.5) to cardiometabolic multimorbidity (CMM), the impact of its components remains unclear. Socioeconomic status (SES) and regional disparities may confound their association. We aim to evaluate the associations between PM2.5 components and CMM and explore how socioeconomic status and regional disparities affect these relationships. METHODS: We recruited 108,941 participants aged 35-76 years from ten cities in eastern China. Individual exposure was assessed using Tracking Air Pollution in China (TAP) data, including PM2.5 and five components: ammonium (NH4+), black carbon (BC), nitrates (NO3-), organic matter (OM), and sulfates (SO42-). Generalized linear models and quantile g-computation models were employed to quantify the effects of PM2.5 components on CMM and to identify key components. Stratified analyses were performed to investigate the modifying effect of SES and regional disparities. RESULTS: For each increase in interquartile range (IQR), BC (odds ratio [OR] 1.37, 95 % CI 1.29-1.47), OM (1.38, 1.29-1.48), NH4+ (1.31, 1.21-1.40), NO3- (1.34, 1.25-1.44), and SO42- (1.28, 1.20-1.38) were positively associated with CMM. Joint exposure to five components was significantly positively associated with CMM (OR: 1.27, 95 % CI: 1.21-1.33), with SO42- having the highest estimated weight, followed by NO3- and BC. These associations were stronger for participants from low socio-economic status and poor regions. CONCLUSION: In summary, we found a stronger hazard effect of PM2.5 and its components on CMM, compared to those suffering from CMDs, particularly among participants with low socioeconomic status and in poor regions. SO42- may be a primary contributor to the association between PM2.5 components and CMM. These findings underscore the importance of prioritizing CMM and targeting SO42-related pollution sources in health policies, particularly amid China's aging population, reducing environmental health inequalities is critical.

Urban-rural disparities in the short-term effects of cold and heat on myocardial infarction mortality in Anhui Province, China.

Non-optimal ambient temperatures are risk factors for myocardial infarction (MI) and urban-rural temperature differences in the context of climate change may have caused and will lead to differential association between temperature and MI. We collected daily mean temperature and daily MI deaths from 1 January 2016 to 31 December 2020 in Anhui Province, China. A distributed lag nonlinear model was performed to estimate the area-specific association of heat and cold (defined as the 2.5th and 97.5th percentile of the daily mean temperature) with MI mortality; the random-effects meta-analysis was then used to pool the effects of cold and heat. We found the risk of MI death due to cold was higher in rural areas [relative risk (RR): 1.13, 95% confidence interval (CI): 1.02-1.26, lag0) than in urban areas (RR: 0.99, 95% CI: 0.80-1.21, lag0), whereas the risk of MI death associated with heat was higher in urban areas (RR: 1.14, 95% CI: 1.03-1.27, lag0) than in rural areas (RR: 1.04, 95% CI: 0.99-1.10, lag0). Our findings may help to develop targeted protective strategies to reduce the adverse effects of cold and heat on cardiovascular disease.

Regulation of Inflammatory Responses of Cow Mammary Epithelial Cells through MAPK Signaling Pathways of IL-17A Cytokines.

The aim of this study is to explore the mechanism of IL-17A infection in the development of bacterial mastitis in dairy cows. In this study, RT-qPCR and ELISA were used to measure the promoting effect of IL-17A on the generation of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and chemokine (IL-8). In addition, Western blot (WB) was applied to measure the influences of IL-17A on the inflammation-related ERK and p38 proteins in the MAPK pathways. The results show that under the stimulation of LPS on cow mammary epithelial cells (CMECs), cytokines IL-1ß, IL-6, IL-8, TNF-α, and IL-17A will exhibit significantly increased expression levels (p < 0.05). With inhibited endogenous expression of IL-17A, cytokines IL-1ß, IL-6, IL-8, and TNF-α will present reduced genetic expression (p < 0.01), with reduced phosphorylation levels of ERK and p38 proteins in the MAPK signaling pathways (p < 0.001). Upon the exogenous addition of the IL-17A cytokine, the genetic expression of cytokines IL-1ß, IL-6, IL-8, and TNF-α will increase (p < 0.05), with increased phosphorylation levels of the ERK and p38 proteins in the MAPK signaling pathways (p < 0.001). These results indicate that under the stimulation of CMECs with LPS, IL-17A can be expressed together with relevant inflammatory cytokines. Meanwhile, the inflammatory responses of mammary epithelial cells are directly proportional to the expression levels of IL-17A inhibited alone or exogenously added. In summary, this study shows that IL-17A could be used as an important indicator for assessing the bacterial infections of mammary glands, indicating that IL-17A could be regarded as one potential therapeutic target for mastitis.

Impaired thyroid hormone sensitivity exacerbates the effect of PM2.5 and its components on dyslipidemia in schizophrenia.

BACKGROUND: Dyslipidemia in schizophrenia causes a serious loss of healthy life expectancy, making it imperative to explore key environmental risk factors. We aimed to assess the effect of PM2.5 and its constituents on dyslipidemia in schizophrenia, identify the critical hazardous components, and investigate the role of impaired thyroid hormones (THs) sensitivity in this association. METHODS: We collected disease data on schizophrenia from the Anhui Mental Health Center from 2019 to 2022. Logistic regression was constructed to explore the effect of average annual exposure to PM2.5 and its components [black carbon (BC), organic matter (OM), sulfate (SO42-), ammonium (NH4+), and nitrate (NO3-)] on dyslipidemia, with subgroup analyses for age and gender. The degree of impaired THs sensitivity in participants was reflected by the Thyroid Feedback Quantile-based Index (TFQI), and its role in the association of PM2.5 components with dyslipidemia was explored. RESULTS: A total of 5125 patients with schizophrenia were included in this study. Exposure to PM2.5 and its components (BC, OM, SO42-, NH4+, and NO3-) were associated with dyslipidemia with the odds ratios and 95 % confidence interval of 1.13 (1.04, 1.23), 1.16 (1.07, 1.26), 1.15 (1.06, 1.25), 1.11 (1.03, 1.20), 1.09 (1.00, 1.18), 1.12 (1.04, 1.20), respectively. Mixed exposure modeling indicated that BC played a major role in the effects of the mixture. More significant associations were observed in males and groups <45 years. In addition, we found that the effect of PM2.5 and its components on dyslipidemia was exacerbated as impaired THs sensitivity in the patients. CONCLUSIONS: Exposure to PM2.5 and its components is associated with an increased risk of dyslipidemia in schizophrenia, which may be exacerbated by impaired THs sensitivity. Our results suggest a new perspective for the management of ambient particulate pollution and the protection of thyroid function in schizophrenia.

Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury.

BACKGROUND: Inflammatory macrophage infiltration plays a critical role in acute kidney disease induced by ischemia-reperfusion (IRI-AKI). Calycosin is a natural flavone with multiple bioactivities. This study aimed to investigate the therapeutic role of calycosin in IRI-AKI and its underlying mechanism. METHODS: The renoprotective and anti-inflammatory effects of calycosin were analyzed in C57BL/6 mice with IRI-AKI and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA-seq was used for mechanism investigation. The molecular target of calycosin was screened by in silico methods and validated by surface plasmon resonance (SPR). Macrophage chemotaxis was analyzed using Transwell and agarose gel spot assays. RESULTS: Calycosin treatment significantly reduced serum creatinine and urea nitrogen and attenuated tubular destruction in IRI-AKI mice. Additionally, calycosin markedly suppressed NF-κB signaling activation and the expression of inflammatory mediators IL-1ß and TNF-α in IRI-AKI kidneys and LPS-stimulated RAW 264.7 cells. Interestingly, RNA-seq revealed calycosin remarkably downregulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was downregulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in silico target prediction, molecular docking, and SPR assay demonstrated that calycosin directly binds to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells. CONCLUSIONS: In summary, calycosin attenuates IRI-AKI by inhibiting MIF-mediated macrophage inflammatory chemotaxis, suggesting it could be a promising therapeutic agent for the treatment of IRI-AKI.

Research progress of acupuncture and moxibustion for the enhanced synergism of chemotherapy. / é’ˆç¸ååŒåŒ–ç–—å®žçŽ°å¢žæ•ˆçš„ç ”ç©¶è¿›å±•.

The application of acupuncture and moxibustion in alleviating the adverse effects of chemotherapy drugs has been widely recognized at home and abroad, but the studies have been rarely summarized for the enhanced anti-tumor effect and its mechanism of acupuncture and moxibustion to synergize the chemotherapy drugs. This paper reviewed the clinical and basic studies on the synergism of chemotherapy with acupuncture and moxibustion in recent years. It was found that chemotherapy synergized with acupuncture and moxibustion can suppress cancer to a certain extent and improve the quality of life in patients. The effect mechanism of acupuncture and moxibustion combined with chemotherapy drugs is related to promoting tumor cell apoptosis, improving the immune and vascular microenvironment, and advancing chemotherapy drug enrichment on the affected area. It provides the evidences and ideas for enhancing the effect of chemotherapy by delivering acupuncture and moxibustion as an adjuvant therapy.

The effect of modified Qiyuan paste on mice with low immunity and sleep deprivation by regulating GABA nerve and immune system.

BACKGROUND: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. METHODS: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin-eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. RESULTS: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. CONCLUSIONS: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions.

Multimorbidity and emergency hospitalisations during hot weather.

BACKGROUND: People with chronic diseases are a commonly listed heat-vulnerable group in heat-health action plans. While prior research identifies multiple health conditions that may increase vulnerability to ambient heat, there is minimal evidence regarding the implications of multimorbidity (two or more chronic diseases). METHODS: From the statewide hospital registry of Queensland, Australia, we identified people aged ≥15 years who had emergency hospitalisation(s) between March 2004 and April 2016 and previously had 0, 1, 2, or ≥3 of five chronic diseases: cardiovascular disease, diabetes, mental disorders, asthma/COPD, and chronic kidney disease. We conducted time-stratified case-crossover analyses to estimate the odds ratio of hospitalisations associated with ambient heat exposure in people with different numbers, types, and combinations of chronic diseases. Ambient heat exposure was defined as a 5 °C increase in daily mean temperature above the median. FINDINGS: There were 2,263,427 emergency hospitalisations recorded (48.7% in males and 51.3% in females). When the mean temperature increased, hospitalisation odds increased with chronic disease number, particularly in older persons (≥65 years), males, and non-indigenous people. For instance, in older persons with 0, 1, 2, or ≥3 chronic diseases, the odds ratios associated with ambient heat exposure were 1.00 (95% confidence interval: 0.96, 1.04), 1.06 (1.02, 1.09), 1.08 (1.02, 1.14), and 1.13 (1.07, 1.19), respectively. Among the chronic diseases, chronic kidney disease, and asthma/COPD, either existing alone, together, or in combination with other diseases, were associated with the highest odds of hospitalisations under ambient heat exposure. INTERPRETATION: While individuals with multimorbidity are considered in heat-health action plans, this study suggests the need to consider specifically examining them as a distinct and vulnerable subgroup. FUNDING: Wellcome.

Efficacy and safety of herbal medicine combined with acupuncture in pediatric epilepsy treatment: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of herbal medicine and acupuncture combination for pediatric epilepsy treatment. METHODS: Databases were searched from their interception until October 2023 to identify randomized controlled trials focusing on the therapeutic efficacy of herbal medicine-acupuncture combination (intervention group) for pediatric epilepsy. The primary outcome was the risk of treatment failure, whereas the secondary outcomes included the risk of post-treatment electroencephalogram (EEG) abnormalities and adverse events. Subgroup analyses were conducted based on the type of herbal compound formulas. Meta-regression analysis was conducted to examine the influence of patient demographics and clinical history on the therapeutic efficacy of herbal medicine-acupuncture combination for pediatric epilepsy. To assess the cumulative evidence, trial sequential analysis (TSA) was performed. RESULTS: The analysis included 10 trials involving a total of 882 pediatric patients. Meta-analysis revealed that the intervention group had a lower risk of treatment failure than the control group (risk ratio [RR] = 0.3, 95% confidence interval [CI]: 0.19-0.47, P<0.00001, I2 = 0%, 10 trials). Subgroup analyses showed that therapeutic efficacy was consistent among the different herbal compound formulas. Meta-regression analysis revealed that the efficacy of the treatments did not significantly vary with patient age, male sex, and duration of seizure history. TSA suggested that herbal medicine-acupuncture combination exerted a robust and conclusive effect on seizure treatment. Although the combined used of herbal medicine and acupuncture was not associated with a lower risk of post-treatment EEG abnormalities (RR = 0.82, 95%CI:0.6-1.11, P = 0.2, 3 trials), the risk of adverse events was reduced (RR = 0.27, 95%CI:0.18-0.41, P<0.00001, 4 trials). CONCLUSION: The meta-analysis suggested that combined use of herbal medicine and acupuncture is a promising and safe clinical approach for pediatric epilepsy treatment. Further large-scale studies are necessary to conclusively determine the efficacy and safety of herbal medicine and acupuncture in pediatric epilepsy treatment.

Does the morphology of residential greenspaces contribute to the development of a cardiovascular-healthy city?

BACKGROUNDS: Greenspaces are indispensable for the construction of a healthy city. Research has shown that greenspaces contribute to the reduction of cardiovascular risks. However, the role of greenspace morphology in the development of a healthy city is not well understood. METHODS: Our study utilized data from a cardiovascular disease screening cohort comprising 106,238 residents in Anhui Province, China, aged between 35 and 75 years. We calculated landscape indices of each participant using high-resolution land cover data to measure the greenness, fragmentation, connectivity, aggregation, and shape of greenspaces. We used a multivariate linear regression model to assess the associations between these landscape indices and triglyceride risk, and employed a structural equation model to explore the potential contributions of heatwaves and fine particulate matter (PM2.5) to this association. RESULTS: Overall, triglyceride was expected to increase by 0.046% (95% CI: 0.040%, 0.052%) with a 1% increase in the percentage of built-up area. Conversely, an increase in the percentage of greenspace was associated with a 0.270% (95% CI: 0.337%, -0.202%) decrease in triglyceride levels. Furthermore, when the total greenspace was held constant, the shape, connectedness, and aggregation of greenspace were inversely correlated with triglyceride levels, with effects of -0.605% (95% CI: 1.012%, -0.198%), -0.031% (95% CI: 0.039%, -0.022%), and -0.049% (95% CI: 0.058%, -0.039%), respectively. Likewise, the protective effect of the area-weighed mean shape index was higher than that of the total amount of greenspace. The stratification results showed that urban residents benefited more from greenspace exposure. Greenspace morphology can minimize triglyceride risk by reducing pollutant and heatwaves, with aggregation having the greatest effect on reducing pollutants whereas fragmentation is more efficient at reducing heatwaves. CONCLUSION: Exposure to the greenspaces morphology is associated with a reduction in triglyceride risk. The study has important practical and policy implications for early health monitoring and the spatial layout of greenspace and will provide scientific information for healthy urban planning by reducing unfavorable health consequences.

Multiple factor assessment for determining resting metabolic rate in young adults.

Existing formulas cannot fully explain the variation of resting metabolic rate (RMR). This study aims to examine potential influencing factors beyond anthropometric measurements and develop more accurate equations using accessible parameters. 324 healthy adults (230 females; 18-32 years old) participated in the study. Height, fat-free mass (FFM), fat mass (FM) and RMR were measured. Menstrual cycle, stress levels, living habits, and frequency of consuming caffeinated foods were collected. Measured RMR were compared with predictive values of the new equations and previous 11 equations. Mean RMR for men and women was 1825.2 ± 248.8 and 1345.1 ± 178.7 kcal/day, respectively. RMR adjusted for FFM0.66FM0.066 was positively correlated with BMI. The multiple regression model showed that RMR can be predicted in this population with model 1 (with FFM, FM, age, sex and daily sun exposure duration) or model 2 (with weight and height replacing FFM and FM). The accuracy was 75.31% in the population for predictive model 1 and 70.68% for predictive model 2. The new equations had overall improved performance when compared with existing equations. The predictive formula that consider daily sun exposure duration improve RMR prediction in young adults. Additional investigation is required among individuals in the middle-aged and elderly demographic.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results.

BACKGROUND AND OBJECTIVES: The popliteal artery is generally regarded as a "no-stent zone". Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease. METHODS: This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)-free rate. RESULTS: The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency. CONCLUSIONS: DCB treatment yielded favorable 12-month clinical primary patency and TLR-free survival outcomes in patients with popliteal artery disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02698345.

Hypoperfusion in Alzheimer's Disease-Prone Regions and Dementia Conversion in Parkinson's Disease.

PURPOSE OF THE REPORT: Although early detection of individuals at risk of dementia conversion is important in patients with Parkinson's disease (PD), there is still no consensus on neuroimaging biomarkers for predicting future cognitive decline. We aimed to investigate whether cerebral perfusion patterns on early-phase 18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane ( 18 F-FP-CIT) PET have the potential to serve as a neuroimaging predictor for early dementia conversion in patients with PD. MATERIALS AND METHODS: In this retrospective analysis, we enrolled 187 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET at initial assessment and serial cognitive assessments during the follow-up period (>5 years). Patients with PD were classified into 2 groups: the PD with dementia (PDD)-high-risk (PDD-H; n = 47) and the PDD-low-risk (PDD-L; n = 140) groups according to dementia conversion within 5 years of PD diagnosis. We explored between-group differences in the regional uptake in the early-phase 18 F-FP-CIT PET images. We additionally performed a linear discriminant analysis to develop a prediction model for early PDD conversion. RESULTS: The PDD-H group exhibited hypoperfusion in Alzheimer's disease (AD)-prone regions (inferomedial temporal and posterior cingulate cortices, and insula) compared with the PDD-L group. A prediction model using regional uptake in the right entorhinal cortex, left amygdala, and left isthmus cingulate cortex could optimally distinguish the PDD-H group from the PDD-L group. CONCLUSIONS: Regional hypoperfusion in the AD-prone regions on early-phase 18 F-FP-CIT PET can be a useful biomarker for predicting early dementia conversion in patients with PD.

Pylephlebitis combined with septic shock secondary to acute nonperforated appendicitis: a case report.

Pylephlebitis, which is a type of septic thrombophlebitis of the portal vein, is a rare and life-threatening complication that commonly occurs following appendicitis. However, nonspecific abdominal complaints and fever can impede the diagnosis of pylephlebitis. Timely use of appropriate antibiotics and anticoagulants is paramount for treating this condition. We present a case of pylephlebitis and septic shock caused by acute nonperforated appendicitis. A 32-year-old man presented with migratory right lower abdominal pain. Blood cultures showed the presence of Escherichia coli. Blood test results showed increased bilirubin concentrations and coagulation factor abnormalities. A computed tomographic abdominal scan showed that the portal vein had a widened intrinsic diameter. After intensive care treatment with antibiotics, antishock therapy, anticoagulants, and other supportive treatments, the infection was monitored, the abdominal pain disappeared, and the jaundice subsided. Laparoscopic appendectomy was performed. Histopathology showed acute suppurative appendicitis, and no abnormalities were observed during the follow-up period after discharge. A multidisciplinary approach is mandatory for the decision-making process in the presence of pylephlebitis caused by appendicitis to obtain a correct diagnosis and prompt treatment. Similarly, the timing of appendectomy is important for minimizing intra- and postoperative complications.