Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article， based on the formulation compatibility analysis technology of "Tangye Jingfa Tu"， clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases， providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines， covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance， Work Injury Insurance， and Maternity Insurance Drug Catalogue （2023） （more than 50% of the total）， were selected for the study. Within the knowledge system of "Tangye Jingfa Tu"， the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally， the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills， Danshen tablets， Qili Qiangxin capsules， Breviscapine tablets， etc.， covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines， salty flavor was the most common （48）， followed by pungent （33）， and sweet （26）. According to the dominant herbal flavor， salty flavor was the most common （37）， followed by pungent （9）， and sour （5）. According to the dominant herbal quantity， salty flavor was the most common （27）， followed by sour （7）， and pungent （5）. Furthermore， Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example， most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen （9/10）， most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver （7/8）， and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys （6/6）. However， the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas， as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty， sour， and pungent flavors， which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart， heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.

ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article， based on the formulation compatibility analysis technology of "Tangye Jingfa Tu"， clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases， providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines， covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance， Work Injury Insurance， and Maternity Insurance Drug Catalogue （2023） （more than 50% of the total）， were selected for the study. Within the knowledge system of "Tangye Jingfa Tu"， the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally， the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills， Danshen tablets， Qili Qiangxin capsules， Breviscapine tablets， etc.， covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines， salty flavor was the most common （48）， followed by pungent （33）， and sweet （26）. According to the dominant herbal flavor， salty flavor was the most common （37）， followed by pungent （9）， and sour （5）. According to the dominant herbal quantity， salty flavor was the most common （27）， followed by sour （7）， and pungent （5）. Furthermore， Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example， most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen （9/10）， most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver （7/8）， and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys （6/6）. However， the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas， as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty， sour， and pungent flavors， which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart， heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

Objective To mine and analyze the routine blood test data of children with allergic rhinitis (AR), identify routine blood parameters related to childhood allergic rhinitis, establish an effective diagnostic model, and evaluate the performance of the model. Methods This study was a retrospective study of clinical cases. The experimental group comprised a total of 1110 children diagnosed with AR at the First Affiliated Hospital of Air Force Medical University during the period from December 12, 2020 to December 12, 2021, while the control group included 1109 children without a history of allergic rhinitis or other allergic diseases who underwent routine physical examinations during the same period. Information such as age, sex and routine blood test results was collected for all subjects. The levels of routine blood test indicators were compared between AR children and healthy children using comprehensive intelligent baseline analysis, with indicators of P≥0.05 excluded; variables were screened by Lasso regression. Binary Logistic regression was used to further evaluate the influence of multiple routine blood indexes on the results. Five kinds of machine model algorithms were used, namely extreme value gradient lift (XGBoost), logistic regression (LR), gradient lift decision tree (LGBMC), Random forest (RF) and adaptive lift algorithm (AdaBoost), to establish the diagnostic models. The receiver operating characteristic (ROC) curve was used to screen the optimal model. The best LightGBM algorithm was used to build an online patient risk assessment tool for clinical application. Results Statistically significant differences were observed between the AR group and the control group in the following routine blood test indicators: mean cellular hemoglobin concentration (MCHC), hemoglobin (HGB), absolute value of basophils (BASO), absolute value of eosinophils (EOS), large platelet ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PLT), absolute values of leukocyte neutrophil (W-LCC), leukocyte monocyte (W-MCC), leukocyte lymphocyte (W-SCC), and age. Lasso regression identified these variables as important predictors, and binary Logistic regression further analyzed the significant influence of these variables on the results. The optimal machine learning algorithm LightGBM was used to establish a multi-index joint detection model. The model showed robust prediction performance in the training set, with AUC values of 0.8512 and 0.8103 in the internal validation set. Conclusion The identified routine blood parameters can be used as potential biomarkers for early diagnosis and risk assessment of AR, which can improve the accuracy and efficiency of diagnosis. The established model provides scientific basis for more accurate diagnostic tools and personalized prevention strategies. Future studies should prospectively validate these findings and explore their applicability in other related diseases.
Humans ; Male ; Female ; Rhinitis, Allergic/blood* ; Child ; Biomarkers/blood* ; Retrospective Studies ; Early Diagnosis ; Child, Preschool ; ROC Curve ; Logistic Models ; Hematologic Tests ; Algorithms ; Adolescent ; Machine Learning