The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

Objective: To explore the prospective association between multidimensional sleep indicators and the risk of newlyonset dental caries, providing a reference for childrens oral healthrelated sleep intervention. Methods: In October 2021, 1 417 students in grades 1 to 4 (aged 6 to 11) from two elementary schools in Bengbu, Anhui Province, were selected by cluster sampling method. Surveys and followup visits were conducted at baseline (T1), November 2022 (T2), May 2023 (T3), and November 2023 (T4), respectively, including parental questionnaires, oral health and physical examination. Bedtime, sleep duration, sleep midpoint, social jet lag, weekend catchup sleep, and sleep habits were collected and calculated. A multifactorial Cox proportional risk regression model was used to analyze the association between multidimensional sleep indicators and newlyonset caries in schoolaged children after 2 years. Results: The prevalence of dental caries in children was 65.1% at baseline, and the prevalence was 59.0% at the end of the 2year followup. Cox proportional risk regression model showed that for every 1point increase in the childrens bedtime resistance, nocturnal awakenings, parasomnias, and daytime sleepiness scores, the risk of newlyonset caries increased by 12% (HR=1.12, 95%CI=1.08-1.15), 22% (HR=1.22, 95%CI=1.15-1.29), 12% (HR=1.12, 95%CI=1.08-1.17), and 15% (HR=1.15, 95%CI=1.12-1.19), respectively; the risk of newlyonset caries increased by 23% for each 1 h increase in the length of weekend catchup sleep (HR=1.23, 95%CI=1.14 -1.33); compared with children who went to bed before 21:00 on school days, those who went to bed later than 22:00 had a 57% higher risk of newlyonset caries (HR=1.57, 95%CI=1.22-2.03). Compared to children who slept adequately (≥9 h/d), those with insufficient sleep had a 67% higher risk of new caries (HR=1.67, 95%CI=1.43-1.95) (P<0.01). Conclusions These findings suggest a significant association between sleep patterns/sleep disorders and the development of childhood dental caries. Incorporating sleep behavior optimization and sleep quality improvement into comprehensive caries prevention and oral health management protocols may represent a promising intervention strategy to enhance childrens oral health outcomes.

Objective: To investigate the impact of temperature changes between neighboring days (TCN) on the mortality risk of respiratory diseases, so as to provide the evidence for the study of deaths from respiratory diseases caused by climate change. Methods: The monitoring data of deaths from respiratory diseases in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance. The meteorological and air pollutant data of the same period were collected from China Meteorological Data Website and ChinaHighAirPollutants dataset. The effect of TCN on the risk of deaths from respiratory diseases was examined using a generalized additive model combined with a distributed lag non-linear model, and subgroup analyses for gender and age were conducted. The disease burden attributed to TCN at different intervals was assessed by calculating attributable fraction. Results: Totally 11 767 deaths from respiratory diseases were reported in Zibo City from 2015 to 2019, including 6 648 males (56.50%) and 5 119 females (43.50%). There were 1 307 deaths aged <65 years (11.11%), and 10 460 deaths aged 65 years and older (88.89%). A monotonically increasing exposure-response relationship was observed between TCN and deaths from respiratory diseases in the general population, females, and the population aged 65 years and older. The 95th percentile of TCN (P95, 3.84 ℃) reached the peak at a cumulative lagged of day 11 (RR=2.063, 95%CI: 1.261-3.376). The results of subgroup analyses showed greater impacts on females and the population aged 65 years and older, with cumulative lagged effects peaking at day 12 (RR=3.119, 95%CI: 1.476-6.589) and day 11 (RR=2.107, 95%CI: 1.260-3.523). The results of attributional risk analysis showed that next-day warming might increase the attributable risk of deaths from respiratory diseases, and next-day cooling might decrease the attributable risk. Conclusion Next-day warming may increase the mortality risk of respiratory diseases, and has greater impacts on females and the population aged 65 years and older.

Endothelial cells in the inner wall of blood vessels respond to physical and chemical signals of the body by regulating vascular homeostasis， vascular tension， cell adhesion， cell proliferation， coagulation resistance and inflammatory factors， to maintain the stability of blood vessels. Angiogenesis is the key condition for tumor evolution， and the pathological mode of tumor angiogenesis provides nutrients and oxygen for tumor growth and promotes its proliferation. In recent years， endothelial cells have participated in tumor vascular infiltration and driven angiogenesis， which is considered to be the point link in tumor metastasis. By regulating metabolic remodeling， vascular endothelial cells provide the materials and energy needed in the process of tumor angiogenesis， and their abnormal metabolic characteristics facilitate their adaption to the changes of tumor microenvironment， which is often regarded as an important basis for tumor angiogenesis. The ''Yin fire'' theory in traditional Chinese medicine， originating from Huangdi's Internal Classic （Huang Di Nei Jing）， originally meant Yin deficiency generates internal heat， and belonged to the category of fire of internal injury. After the deduction and changes by physicians over the ages， the pathogenesis of ''spleen and stomach Qi deficiency-Yin fire rising-Qi and fire disharmony'' was gradually formed. The pathogenesis of metabolic remodeling of endothelial cells manifests the pathological characterization of Yin fire in an objective way， which is consistent with the disease state of uncontrolled and hyperactive tumor neovascularization. Changes in spleen and stomach Qi deficiency as well as imbalance of Qi movement lead to the failure of water and food in distribution， and thus metabolic disorders occur. Long term retention turns in phlegm and blood stasis， which combat with blood vessels， and result in abnormal local environment （formation of tumor microenvironment）， adverse pulse channel （imbalance of endothelial cell metabolism）， and tumor neovascularization. Under the guidance of ''Yin fire'' syndrome elements and by focusing on the correlation between Qi and fire， prescriptions are made based on the treatment method of ''strengthening the body and regulating Qi'' to regulate the metabolic function of endothelial cells， thus achieving a relatively balanced state of the body and inhibiting tumor angiogenesis. As a result， this study， centering on the metabolic remodeling of endothelial cells and ''Yin fire'' theory， elucidated the academic ideas， with the purpose of providing some theoretical support for the intervention of tumor vascularization by Chinese medicine.

Objective: To examine the impact of heat waves and cold spells on the incidence of hemorrhagic stroke, so as to provide insights into prevention of hemorrhagic stroke. Methods: Data pertaining to the incidence of hemorrhagic stroke in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance, and the meteorological data during the period from 2015 to 2019 were captured from National Meteorological Information Center of China. The air quality index (AQI) was collected from the National Daily Report of Urban Air Quality in China. Heat wave was defined as the highest daily temperature that was no less than the 90th percentile (P90), P92.5, P95 and P97.5 of the highest daily temperature in the warm season for at least 2, 3 or 4 days, and cold spell was defined as the lowest daily temperature that was no more than the P10, P7.5, P5 and P2.5 of the lowest daily temperature in the cold season for at least 2, 3 or 4 days. The effect of heat waves and cold spells on the incidence of hemorrhagic stroke was evaluated using a generalized additive model and described with relative risk (RR) and its 95%CI. Results: A total of 8 844 case with first-onset hemorrhagic stroke were recorded in Zibo City from 2015 to 2019. The lowest daily temperature that was no more than P10, P7.5 or P5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 or P7.5 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.187, 95%CI: 1.031-1.366; highest RR=1.242, 95%CI: 1.042-1.480), and after adjusting the effect of daily mean temperature, the lowest daily temperature that was no more than P10 or P7.5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.236, 95%CI: 1.009-1.513; highest RR=1.274, 95%CI: 1.023-1.585). However, there was no significant association between heat waves and the risk of hemorrhagic stroke. Conclusion Cold spells may increase the risk of hemorrhagic stroke, while no significant association is examined between heat waves and the risk of hemorrhagic stroke.

Cervical cancer is a gynecological malignant tumor with a high incidence in the world. With the insidious onset and lack of obvious symptoms and signs in the early stage， 13% of cervical cancer patients are diagnosed in the advanced stage of the disease， and the 5-year survival rate of metastatic cervical cancer is only 16.5%. So far， surgery and radiotherapy/chemotherapy are still the basic means for the treatment of cervical cancer. However， with the emergence of toxicity， drug resistance， and other side effects， there are still some limitations in the clinical application of these therapies. In recent years， natural compounds represented by polysaccharides have been found to have a significant anti-cervical cancer effect， which has attracted extensive attention from researchers in China and abroad. Widely distributed in the roots， stems， leaves， flowers， and fruits of higher plants， plant-based polysaccharides are important components of natural polysaccharides， as well as multimers with a complex structure and biological response regulators， which have been widely studied in the fields of cancer， cardiovascular， endocrine， and other diseases. This study reviewed the research on the anti-cervical cancer effect and mechanism of natural plant-derived polysaccharides by consulting the literature in the past 20 years to bring breakthroughs in the research and development of anti-cervical cancer new drugs. Through the literature review， the results indicated that natural plant-derived polysaccharides could exert anti-tumor effects by inhibiting cell proliferation， promoting apoptosis， inhibiting invasion and migration， promoting autophagy， arresting cell cycle of cervical cancer cells， regulating epithelial-mesenchymal transition （EMT）， resisting oxidative stress， inhibiting tumor angiogenesis， improving immunomodulatory activity， and regulating signaling pathways. It should be noted that in the current research on natural plant-derived polysaccharides against cervical cancer， the bioavailability of some natural polysaccharides is low and a considerable proportion of the research is limited to the in vitro experiment. Therefore， it is urgent to carry out more clinical experimental studies on the anti-cervical cancer of natural plant-based polysaccharides to obtain a more reliable theoretical and practical basis.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective To evaluate the migration of plutonium aerosol caused by α recoil. Methods In this paper, the recoil deposition and Brownian motion of plutonium-containing nanoaerosols were simulated by Monte Carlo method. The recoil angle and the vertical first landing time of Brownian motion in the process of settling were sampled, and then the lateral displacements of Brownian motion were sampled to determine the final settling position of aerosol. Results For aerosols with particle sizes of 10-50 nm, the maximum migration distance of a single recoil settling was 1.39 μm. Brownian motion increased the migration capacity. Although there was a high likelihood that aerosols settled within 100 μm, there remained a slight probability of long-term suspension in the air. Conclusion The α recoil is one of the mechanisms of plutonium aerosol migration. An important mechanism for long-distance migration of nanoaerosols is that Brownian motion after recoil may cause them to suspend for a long time.

Objective: To investigate the epidemiological characteristics of premature eruption of permanent molars and its aasociation with body mass index (BMI), to provide a reference for childhood oral health promotion. Methods: A total of 861 children aged 9 to 12 years from two primary schools in Bengbu City were selected by cluster sampling method. Parental questionnaire was administered to collect socio demographic information. The eruption of second permanent molars were examined. Data was analyzed by multivariate Logistic regression model and margins command. Results: The detection rate of premature eruption of second permanent molars was 26.5%(228), 27.5% in boys and 24.9% in girls( χ 2=0.73, P =0.39). Early detection rate of second permanent molars (39.0%) was significantly higher in obese group than normal weight group (21.5%)( χ 2=21.85, P <0.01). Logistic regression analysis showed that obesity was positively correlated with the risk of premature eruption of second permanent molars( OR= 3.55 , 95%CI=2.14-5.87, P <0.01). Overweight was not associated with higher risk of premature eruption of second permanent molars( OR=1.64, 95%CI=0.95-2.81, P =0.07). Being female was associated with higher risk of premature eruption of second permanent molars compared to age matched peers( OR=2.19, 95%CI=1.42-3.39, P <0.01). Conclusion Childhood obesity is associated with higher risk for premature eruption of second permanent molars. Girls are more likely to have second permanent molar erupted in advance compared to age matched boys.

Objective:By exploring the source of children's total fluoride intake and the relationship between children's total fluoride intake and dental fluorosis prevalence, to calculate the benchmark dose (BMD) of children's total fluoride intake and its 95% confidence lower limit (BMDL), and to provide the basis for revision of "Total Fluoride Intake for Inhabitants" (WS/T 87-2016).Methods:The villages that had water improvement for 5 years and more in 6 provinces of Jiangsu, Shandong, Hebei, Anhui, Henan and Shaanxi were selected as survey sites in April 2014. The water fluoride content of these villages was 0.3 - 3.0 mg/L, tap water samples from the centralized water supply were collected, and fluoride content was detected by ion selective electrode method. Children aged 8 to 12 years were selected, children's dental fluorosis was checked by Dean's method. Children's dietary and drinking water volume were surveyed by duplicate portion study (measurement for 3 d), and dietary fluoride content was detected according to the "Method for Determination of Fluorine in Foods". The mean and standard deviation of drinking water fluoride intake, dietary fluoride intake, and total fluoride intake were measured. According to the dose-response relationship between children's total fluoride intake and the detection rate of dental fluorosis, BMD and BMDL were calculated, and the reference dose (RfD) was calculated based on BMDL.Results:The mean of water fluoride of all 29 villages was 1.26 mg/L (from 0.41 to 2.85 mg/L). Totally 3 043 children aged 8 to 12 years were checked, and the detection rate of dental fluorosis was 30.2% (919/3 034). The lowest detection rate of dental fluorosis was 2.0% (2/100) and the highest was 71.4% (30/42) in the 29 villages. The children's dietary and drinking water volume of 769 person-time aged 8 to 12 years were surveyed, the children's daily drinking water fluoride intake, dietary fluoride intake, and total fluoride intake were (0.83 ± 0.66), (1.13 ± 0.61) and (1.96 ± 0.89) mg/d, respectively. The BMD of children's daily total fluoride intake was 2.43 mg, the BMDL was 2.21 mg, and the RfD was 2.21 mg.Conclusion:The BMD of 8 to 12 years old children's daily total fluoride intake is the same as the allowable limit (2.4 mg) of the national standard "Total Fluoride Intake for Inhabitants" (WS/T 87-2016).