BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seri-ously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seriously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P＜0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P＜0.05),the brain neuron damage was alleviated(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P＜0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.

ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg^-1）， valsartan capsule group （10.29 mg·kg^-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L^-1 glucose）， high glucose group （35 mmol·L^-1 glucose）， DMSO group （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS group （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.

BACKGROUND:Currently,a variety of mesenchymal stem cells have been confirmed to have the effect of promoting wound repair,but there is still a lack of relevant research on whether placenta-derived mesenchymal stem cells can promote acute skin wound healing. OBJECTIVE:To investigate the effect of placenta-derived mesenchymal stem cell transplantation on the healing of acute skin wound in rats. METHODS:Twenty SD rats were divided into PBS group and stem cell group by the random number table method,with 10 rats in each group.All rats were selected to establish a full-thickness skin defect model.In the PBS group and stem cell group,PBS buffer and placenta-derived mesenchymal stem cells were immediately injected on the wound surface and wound margin immediately and on day 8 after modeling.The wound healing was observed immediately and on days 2,4,6,8,10,12,and 14 after modeling.The skin tissue of the wound surface was taken on day 14 and treated with hematoxylin-eosin staining,Masson staining,immunohistochemical staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The wound surface of the rats in each group decreased with the prolongation of treatment time.The wound healing rate and wound epithelization rate of the stem cell group at 14 days were higher than those of the PBS group(P<0.01),and the wound contracture rate was lower than that of the PBS group(P<0.01).(2)The results of hematoxylin-eosin staining showed that the skin wound healing of the stem cell group was better than that of the PBS group;the degree of wound epithelization was higher,and the morphology of collagen fibers was close to that of normal skin.(3)Masson staining results showed that compared with the PBS group,collagen fibers in the skin wound tissue of the stem cell group were significantly increased and thicker,and the content of collagen fibers in the new tissue was significantly higher than that of the PBS group(P<0.01).(4)Immunohistochemical staining showed that the number of new capillaries in the stem cell group was higher than that in the PBS group(P<0.01),while the expressions of tumor necrosis factor-α and interleukin-6 were lower than those in the PBS group(P<0.01).(5)Immunofluorescence staining showed that the number of M2 macrophages in the new wounds of the stem cell group was higher than that of the PBS group(P<0.01),while the number of M1 macrophages was less than that in the PBS group(P<0.01).These findings indicate that placenta-derived mesenchymal stem cells can accelerate skin wound healing,promote wound epithelization,and reduce wound contracture,which may be related to the promotion of capillary angiogenesis,regulation of collagen fiber production,inhibition of inflammation,and regulation of macrophage polarization to M2 type.

ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg^-1）， and losartan capsules （10.29 mg·kg^-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L^-1）， high glucose （35 mmol·L^-1）， DMSO （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasomes in curcumin-induced reduction of sevoflurane-induced postoperative cognitive dysfunction in rats.Methods:Forty SPF healthy male Sprague-Dawley rats, aged 17-18 months, with body mass index of 580-600 g, were divided into 4 groups ( n=10 each) by a random number table method: control group (C group), postoperative cognitive dysfunction group (P group), curcumin group (CU group), and curcumin+ NLRP3 inflammasome activator group (CN group). The rat model of postoperative cognitive dysfunction was prepared by inhaling 1.5% sevoflurane to explore the abdominal cavity. Curcumin suspension 300 mg/kg was given by intragastric administration in CU group and CN group, and the rats received intragastric administration of nidrisin sodium 5 mg/kg simultaneously in CN group, once a day for 6 consecutive days. Rats received the equal volume of normal saline instead in C group and P group. The frequency of crossing the original platform and time spent in the target quadrant were measured by the Morris water maze test. The histopathological changes of hippocampus were observed by HE staining, neuronal apoptosis was detected by TUNEL staining, and the expression of NLRP3, Bcl-2 and Bax was detected by Western blot. Results:Compared with C group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in P group ( P<0.05). Compared with P group, the frequency of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the apoptosis rate of neurons was decreased, and the expression of NLRP3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in CU group ( P<0.05). Compared with CU group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in CN group ( P<0.05). Conclusions:The NLRP3 inflammasome is involved in curcumin-induced reduction of postoperative cognitive dysfunction in sevoflurane-anesthetized rats.

With the increasing global prevalence of tree pollen allergies, there has been a significant impact on the quality of life for populations. In North and Central China, birch pollen, cypress pollen, and plane tree pollen are the most common allergens for springtime pollen allergy sufferers. The distribution of plants and patterns of pollen transmission in different geographical areas result in varying pollen exposure outcomes, further complicating the challenges in diagnosis and individualized treatment. This article delves into the research progress and clinical application of tree pollen allergies based on the "Molecular Allergology User′s Guide 2.0 (MAUG 2.0) " published by the European Academy of Allergy and Clinical Immunology (EAACI). It discusses major allergen families and component proteins of tree pollen such as PR-10 proteins, profilins, polcalcins, as well as cross-reactive components that may cause pollen-food allergy syndrome. Allergen component diagnostics can distinguish true allergy sufferers from those with multiple allergen reactions, enabling more targeted selection of allergens for specific immunotherapy, thus enhancing treatment effectiveness. Bet v 1 and Cup a 1, for instance, are specific indicators for immunotherapy in birch and cypress allergy patients. Overall, this article provides cutting-edge information for professionals in the field of tree pollen allergies, offering in-depth exploration of tree pollen allergen component proteins, clinical manifestations, and treatment-related research, aiding in better understanding and addressing the challenges of tree pollen allergies.

Grasses are extensively cultivated worldwide, with the three most common allergenic grass pollen subfamilies being Pooideae in temperate regions, Chloridoideae and Panicoideae in subtropical areas. This article delves into the research progress and clinical applications of grass pollen allergy as delineated in the "Molecular Allergology User′s Guide 2.0" issued by the European Academy of Allergy and Clinical Immunology (EAACI). It compiles epidemiological data on grass pollen, allergenic components, clinical manifestations, and treatment guidelines from both domestic and international sources, providing cutting-edge insights and scientific perspectives for professionals in the field of pollen allergy. The aim is to enhance the understanding of allergenic components, distinguishing between grass pollen allergy and pan-allergen responses with precision through advanced component-resolved diagnostic techniques. This serves to foster novel approaches to characterizing the unique sensitization patterns of grass pollen allergens in China, thereby offering more personalized and targeted diagnostic and therapeutic strategies for clinical practice in the region.

Cockroaches are one of the most common indoor allergens worldwide, and exposure to cockroach allergens (such as the insect body, debris, and secretions) can trigger severe allergic rhinitis and(or) asthma. Currently, the World Health Organization (WHO)/International Union of Immunological Societies (IUIS) has identified 32 allergenic components in cockroaches, but none of these allergens have shown a clear immunodominance. The sensitization rate to cockroach allergens shows significant variability across different regions and populations and exhibits cross-reactivity with various invertebrates, increasing the complexity of clinical diagnosis and treatment. This article delves into the "Molecular Allergology User′s Guide 2.0"(MAUG 2.0) published by the European Academy of Allergy and Clinical Immunology (EAACI) and the research progress on cockroach allergies both domestically and internationally. It elucidates the crucial role of allergen component diagnostic technology in enhancing the diagnosis and treatment of cockroach-induced allergic diseases, efficiently assisting clinicians in identifying common sensitizations and cross-reactivities, thereby offering patients more accurate diagnoses and personalized treatment plans.