Background Meteorological factors are among the key extrinsic triggers for the onset and exacerbation of cardiovascular and cerebrovascular diseases (CVD). Against the backdrop of sustained global warming, elucidating the impact of ambient temperature and atmospheric pressure on CVD, especially on pre-hospital CVD emergent events, has become imperative for evidence-based prevention and emergency preparedness. Objective To quantify the temporal trends of daily mean temperature and atmospheric pressure and their associations with pre-hospital CVD emergent events in Yantai, and to explore effect modification by demographic subgroups and geographic areas, thereby providing an empirical basis for the rational allocation of emergency medical resources. Methods Pre-hospital CVD emergency data from January 1, 2016 to December 31, 2022 were selected from the Yantai 120 Emergency Medical Command System. Synchronous meteorological factors and environmental pollutant data were obtained from the websites of the National Oceanic and Atmospheric Administration and the National Centers for Environmental Information of the United States. Time-series analysis combined with distributed lag non-linear model was used to analyze the association between daily temperature, atmospheric pressure, and pre-hospital CVD emergencies. Average annual percentage changes (AAPC) were calculated using Joinpoint (version 5.2.0.0) to reflect temporal trends. Spearman correlation analysis was employed to screen variables with low collinearity for inclusion in the multi-pollutant adjusted models. Results From 2016 to 2022, a total of 268275 pre-hospital CVD emergency cases were recorded in Yantai City, showing an increasing annual trend (AAPC=7.16%, P=0.002). Emergency volume, daily temperature, atmospheric pressure, and PM₁₀ displayed marked seasonal patterns, with summer bottoms and winter peaks for emergencies, daily temperature higher in summer and lower in winter, and the inverse for atmospheric pressure. Correlation analysis showed that both daily temperature and atmospheric pressure were positively correlated with O₃, with correlation coefficients of 0.745 and 0.723, respectively; negatively correlated with PM_2.5, with correlation coefficients of −0.246 and −0.235, respectively; and negatively correlated with PM₁₀, with correlation coefficients of −0.241 and −0.229, respectively (P < 0.05). A U-shaped correlation was revealed between daily temperature and pre-hospital CVD emergency risk. Using 24 °C as the reference, risk was elevated at both low and high daily temperatures, with the strongest cold effect at –11 ℃ (RR=1.53, 95%CI: 1.35, 1.73) and strongest heat effect at 30 ℃ (RR=1.06, 95%CI: 1.01, 1.11); cold effects were prolonged (lag0–14d) compared to heat effects. Atmospheric pressure exhibited a positive association with emergencies; using a median of 1012.2 hPa as the reference, the maximum risk occurred at 1037 hPa (RR=1.25, 95%CI: 1.03, 1.52), with a 0–5 d lag. In the subgroup analysis, the impact of low temperature was more pronounced among females (RR_{−9 ℃}=1.66), people over 60 years (RR_{−9 ℃}=1.91), and rural residents (RR_{−9 ℃}=1.76). High atmospheric pressure significantly increased the risk of pre-hospital CVD emergency among females (RR_{1035 hPa}=1.54), people under 18 years (RR_{1035 hPa}=3.62), and rural residents (RR_{1035 hPa}=1.46). The sensitivity analysis results indicated that, after excluding the impact of pandemic and the degrees of freedom for time variations, the effects of daily average temperature and atmospheric pressure on pre-hospital CVD emergency volume were consistent with the primary analysis findings. Conclusion Both non-optimal temperature and atmospheric pressure significantly increase the pre-hospital CVD emergency volume; therefore, emergency medical services should develop targeted response protocols, optimize resource allocation, and intensify public health education to mitigate the pre-hospital burden attributable to temperature and pressure fluctuations.

ObjectiveTo investigate the protective effect of Dabupi Tang （DBPT） against radiation-induced lung injury （RILI） and to elucidate whether its mechanism involves modulating the inflammatory response mediated by the Janus kinase 1 （JAK1）/signal transducer and activator of transcription 6 （STAT6） signaling pathway. MethodsForty-eight SPF-grade male SD rats were randomized into 6 groups （n=8）： blank control， model， high-dose （24.28 g·kg^-1） DBPT， medium-dose （12.14 g·kg^-1） DBPT， low-dose （6.07 g·kg^-1） DBPT， and high-dose DBPT + AG490 （a JAK1/STAT6 inhibitor， 5 mg·kg^-1）. After two consecutive weeks of gavage， other groups except the blank control group received single-dose irradiation with 8 Gy X-ray to the right lung for the modeling of RILI. Samples were collected 24 h post-irradiation. Hematoxylin-eosin （HE） staining was used to observe lung histopathology. Serum levels of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and transforming growth factor-β （TGF-β） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of JAK1， STAT6， phosphorylated JAK1 （p-JAK1）， and phosphorylated STAT6 （p-STAT6） in the right lung tissue were determined by immunohistochemistry and Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to analyze the transcription levels of JAK1， STAT6 mRNA. ResultsCompared with the blank control group， the model group showed typical pathological features （alveolar structure destruction， interstitial hyperemia， and lymphocyte infiltration） of RILI. Compared with the model group， the DBPT groups （especially the high- and medium-dose groups） exhibited significantly alleviated lung tissue damage. Compared with the blank control group， the model group exhibited elevated serum levels of TNF-α， IL-8， IL-6， and TGF-β （P<0.01）， which were reduced by DBPT in a dose-dependent manner （P<0.05， P<0.01）. Compared with the blank control group， the model group showed decreased p-JAK1/JAK1 and p-STAT6/STAT6 ratios in the lung tissue （P<0.01）. Compared with the model group， DBPT intervention （especially the high dose） increased the p-JAK1/JAK1 and p-STAT6/STAT6 ratios （P<0.05， P<0.01）. Compared with the high-dose DBPT group， high-dose DBPT + AG490 reversed the protective effect of DBPT， leading to aggravated lung injury and increased pro-inflammatory cytokine levels （P<0.05）， confirming the critical role of this pathway. ConclusionDBPT exerts a significant protective effect against RILI. It may activate the JAK1/STAT6 signaling pathway to reduce the release of pro-inflammatory cytokines， thus alleviating RILI. This study suggests that the JAK1/STAT6 pathway is a potential therapeutic target for DBPT in the prevention and treatment of RILI.

Objective To investigate the effects of different doses of Yiyi Ren aqueous prepara-tion on blood lipid regulation and spleen-strengthening and dampness-eliminating effects in hyperlipi-demia rats with syndrome of spleen deficiency and excessive dampness.Methods Sixty SD male rats were randomly divided into blank control group,model group,low-dose,medium-dose,high-dose Yiyi Ren aqueous preparation groups,and positive drug control group,with 10 rats in each group.A hyperlipidemia rat model with syndrome of spleen deficiency and excessive dampness was estab-lished by feeding with a high-fat diet for 21 consecutive days combined with a damp bedding environment.After drug administration,behavioral tests such as grip strength,weighted swimming test,and open field test were conducted;changes in body weight in each group were observed;serum levels of total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-den-sity lipoprotein cholesterol(LDL-C)were detected;levels of vasoactive intestinal peptide(VIP),an-tidiuretic hormone(ADH),and aldosterone(ALD)were measured by enzyme-linked immunosorbent assay(ELISA).Results Compared with the blank control group,the model group showed decreased HDL-C,grip strength,exhaustive swimming time,and total distance,as well as increased TC,TG,LDL-C,ADH,ALD,and VIP(P＜0.05).Compared with the model group,TC,TG,and LDL-C levels were decreased in the medium-dose,high-dose Yiyi Ren aqueous preparation groups,and the positive drug control group,while the HDL-C levels were increased in the low-dose,medium-dose,and high-dose Yiyi Ren aqueous preparation groups and the positive drug control group(P＜0.05).Compared with the model group,the high-dose Yiyi Ren aqueous preparation group showed in-creased grip strength,exhaustive swimming time and total distance and decreased serum ADH levels(P＜0.05).Compared with the model group,the medium and high-dose Yiyi Ren aqueous prepa-ration groups showed decreased serum ALD and VIP levels(P＜0.05).Conclusion Yiyi Ren aqueous preparation has an effect on regulating blood lipid levels in hyperlipidemia rats with syn-drome of spleen deficiency and excessive dampness,and it can alleviate physical fatigue,improve abnormal exploratory behavior,and maintain normal water metabolism and motor function in rats.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Type 2 diabetes mellitus(T2DM) is a prevalent metabolic and endocrine disorder. Long-term hyperglycemia can lead to severe chronic complications, imposing substantial economic burdens on both society and patients. Despite the availability of various hypoglycemic agents for clinical use, these agents often fail to meet the therapeutic needs of T2DM and its complications. Consequently, there is an urgent need for novel therapeutic strategies and drugs. Lithocarpus litseifolius(L. litseifolius), commonly referred to as "cordyceps on trees", has a long history of use in traditional medicine and can be applied in tea, sugar, and medicine. Research indicates that L. litseifolius extracts are rich in dihydrochalcones, including trilobatin, phloridzin, and phloretin, which exhibit a range of pharmacological activities, such as anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, and cardioprotective effects. These properties suggest potential applications in the treatment of T2DM and its complications. This review systematically compiled and organized the relevant literature from the past decade on dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts. It highlighted recent research progress regarding their role in treating T2DM and its complications through mechanisms such as reducing insulin resistance, regulating glucose transport, improving glucose and lipid metabolism, modulating enzyme activity, regulating gut microbiota, and alleviating inflammation and oxidative damage. The purpose of this review is to provide a reference and basis for future research on the prevention and treatment of T2DM and its complications using dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts.
Chalcones/chemistry* ; Diabetes Mellitus, Type 2/metabolism* ; Humans ; Animals ; Elaeocarpaceae/chemistry* ; Drugs, Chinese Herbal/therapeutic use* ; Hypoglycemic Agents/chemistry* ; Plant Extracts/chemistry*

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer