Background In the context of climate change, the health burden associated with non-optimal temperature is becoming increasingly substantial. Emergency ambulance calls (EACs) are a sensitive indicator of acute health effects. However, most previous studies have relied on daily mean temperature (MT) or a single thermal stress indicator, and it remains unclear whether different temperature indicators yield materially different estimates of the health burden attributable to non-optimal temperature. Objective To compare multiple temperature indicators in evaluating the attributable burden of EACs associated with non-optimal temperature in Dezhou City, Shandong Province. Methods Daily EACs records and corresponding meteorological data in Dezhou from 2014 to 2023 were collected. A time-stratified case-crossover design with conditional logistic regression, combined with distributed lag non-linear models (DLNM), was employed to examine the exposure-response relationships and population attributable burden of EACs associated with the percentiles of daily MT and 12 commonly used thermal stress indicators. Results During the study period, a total of 952989 EACs were recorded in Dezhou. For all temperature indicators, the cumulative exposure-response curves showed a V-shaped pattern. Among the attributable fraction (AF) estimates, only those derived from the universal thermal climate index for outdoor shaded space (UTCI3) and wet-bulb temperature (WBT) were significantly lower than the estimates based on MT (P < 0.05); no statistically significant differences were observed for the other indicators. The AF based on MT was 5.24% (95%CI: 4.34%, 6.16%), and the attributable burden was mainly driven by cold temperatures (AF=3.57%, 95%CI: 2.65%, 4.48%). Spatially, high heat-attributable EACs rates per 1000 population were primarily concentrated in the central and southern Dezhou, whereas areas with high cold-attributable EACs rates were more dispersed. The overall spatial pattern of EACs attributable to non-optimum temperatures was more consistent with the distribution of cold-related risks. Subgroup analysis showed that, across susceptible population groups, the AF estimates derived from most thermal stress indicators did not differ significantly from those based on MT. Conclusion In Dezhou, most thermal stress indicators produce attributable burden estimates for EACs associated with non-optimal temperature that are similar to those based on daily MT, and cold temperatures contribute more to the overall attributable burden. The spatial distribution of EACs attributable to non-optimal temperature is dispersed, whereas heat-attributable hotspots are concentrated in central and southern Dezhou.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Objective To assess the viability and efficacy of employing automated segmentation for whole breast radiotherapy with simultaneous integrated boost to the medial tumor beds,a comparative analysis was conducted on the disparities in geometry,dosimetry,and working time between the auto-segmentation(AS)and manual segmentation(MS)groups.Methods A total of 30 patients with early breast cancer,who had undergone conserving surgery and received hypofractionated radiotherapy with a boost to the medial tumor bed,were enrolled from the First People's Hospital of Zunyi.AccuContour software was used in the AS group to obtain the whole breast planning target volume and cardiopulmonary structure.Geometric differences between AS and MS groups were assessed using Dice similarity coefficient(DSC)and 95%Hausdorff distance(95HD).Subsequently,a comparison was made between the two groups regarding target and cardiopulmonary dosimetry for PlanA and PlanM.Additionally,the time spent by each group was also compared.Results The DSC of PGTV,PTV,lung,and heart were 0.94(0.91,0.96),0.88(0.86,0.91),0.98(0.97,0.98)and 0.94(0.93,0.95),respectively.And the 95 HD(cm)were 0.25(0.20,0.33),0.99(0.56,1.20),0.29(0.25,0.35)and 0.50(0.50,0.59)respectively.The dosimetric results showed that the V95,D95,and Dmean of PGTV and PTV in the AS group were significantly lower than those in the MS group(P<0.05);while the V20 and MLD of the left lung were significantly higher(P<0.05).No significant difference was observed in cardiac dose between the two groups.The mean absolute differences of PGTV and cardiopulmonary dose parameters between the two groups were less than 1 Gy/1%,respec-tively.In terms of work efficiency,the AS approach substantially reduced contouring and planning time with over 70%of cases approved within two days.Conclusions The differences in geometric and dosimetric parameters between the auto-segmentation and manual segmentation groups were found to be negligible for whole breast radiotherapy with medial tumor bed boost patients.It is recommended that the PTV be manually modified prior to plan optimiza-tion,leading to a significant improvement in work efficiency.

Objective:To investigate the effect of sodium butyrate (NaB) on renal and intestinal injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) and its related mechanism.Methods:Twenty-four domestic healthy male swines were randomly divided into 3 groups: sham group ( n=6), CA-CPR group ( n=10) and NaB group ( n=8). The animals only underwent operational preparation in the sham group. The animal model of CA and CPR was established by 9 min of ventricular fibrillation induced by electrical stimulation in the ventricle and then 6 min of CPR in the CA-CPR and NaB groups. At 5 min after resuscitation, a dose of 75 mg/kg of NaB was intravenously infused for 1 h in the NaB group, and meanwhile the same volume of vehicle was intravenously infused in the sham and CA-CPR groups. At 1, 2, 4, and 24 h after resuscitation, blood samples were collected to detect the renal and intestinal injury biomarkers, such as creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP), and diamine oxidase (DAO). At 24 h after resuscitation, renal and intestinal tissue specimens were harvested to detect the protein markers of cell autophagy including microtubule-associated protein light chain 3 Ⅱ (LC3Ⅱ) and p62 expression, and also renal and intestinal apoptosis. Statistical analysis was performed by SPSS software, and continuous variables were compared with one-way analysis of variance among the groups. Results:After CA-CPR, the renal and intestinal injury biomarkers including Cr, BUN, IFABP, and DAO were significantly increased at all time points after resuscitation in the CA-CPR and NaB groups compared with the sham group (all P<0.05). The injury biomarkers mentioned-above were significantly lower at all time points after resuscitation in the NaB group than in the CA-CPR group [Cr (μmol/L): (90±5) vs. (127±9) at 1 h, (135±14) vs. (168±9) at 2 h, (174±10) vs. (211±12) at 4 h, (192±10) vs. (253±13) at 24 h; BUN (mmol/L): (10.5±1.0) vs. (12.3±1.0) at 1 h, (12.2±1.2) vs. (15.3±0.9) at 2 h, (13.6±1.3) vs. (18.3±1.2) at 4 h, (15.4±1.4) vs. (21.5±1.4) at 24 h; IFABP (pg/mL): (502±33) vs. (554±32) at 1 h, (574±52) vs. (644±41) at 2 h, (646±44) vs. (732±43) at 4 h, (711±42) vs. (828±42) at 24 h; DAO (U/mL): (8.6±1.0) vs. (10.5±0.9) at 1 h, (10.6±1.2) vs. (12.8±1.0) at 2 h, (12.1±1.0) vs. (15.0±1.0) at 4 h, (14.1±1.1) vs. (17.6±1.0) at 24 h, (all P<0.05)]. Renal and intestinal tissue detection indicated that cell autophagy and apoptosis were significantly increased after resuscitation in the CA-CPR and NaB groups compared with the sham group, which was indicated by significantly increased LC3Ⅱ and decreased p62 expression, and markedly elevated apoptosis index (all P<0.05). However, cell autophagy and apoptosis in the kidney and intestine were significantly milder after resuscitation in the NaB group than in the CA-CPR group [renal LC3 Ⅱ: (1.15±0.17) vs. (2.23±0.31), p62: (1.60±0.10) vs. (1.17±0.08), apoptosis index (%): (21.2±5.3) vs. (50.9±7.9); intestinal LC3 Ⅱ: (1.03±0.17) vs. (1.71±0.21), p62: (1.30±0.29) vs. (0.79±0.29), apoptosis index (%): (25.6±6.1) vs. (61.7±10.7), all P<0.05]. Conclusions:NaB could alleviate the severity of renal and intestinal damage after CA-CPR in swine, and its protective mechanism may be related to the inhibition of cell autophagy and apoptosis.

Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the amino-thiol cysteamine and pantothenic acid (coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared (NIR) fluorescent probe (DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered from herbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.

In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed. Methodologies included HPLC-PDA, HPLC-VWD and UHPLC-MS , combined with principal component analysis (PCA) and partial least squares regression techniques (PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated . PLSR analysis revealed significant positive correlations ( = 0.5795) between the contents of triterpenes , , , and and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.

The glycoproteins in the biological sample are low abundance and are susceptible to be inhibited and interfered by other non-glycoproteins.An enrichment step is usually required before the glycoprotein analysis, but the operation steps of conventional solid-phase-based glycoprotein enrichment methods are difficult to be compatible with the most classical enzyme-linked immune sorbent assay (ELISA) technique.In this study, a novel water-soluble dendrimer based boronic acid capture (DBC) material was developed using PAMAM 4.0 as the carrier and boronic acid as the affinity group.The method was applied to the detection of glycoproteins in human liver microsomes using ELISA.In this study, the DBC enrichment conditions were optimized by model glycoprotein, and then its sensitivity and anti-interference ability were investigated.This method was applied to the enrichment of glycoproteinsin human liver microsomal.The results showed that the enrichment selectivity of DBC for glycoprotein could be up to 100000 folds, and the enrichment signal of glycoprotein could be increased by 100 times.Therefore, the ELISA method using DBC as a novel enrichment material for glycoprotein had high sensitivity and selectivity in detection of biological samples with only one simple incubation step, which was useful for glycoproteins researches.

Objective To investigate the changes of caries susceptibility factors during the transition from caries-free to caries in three-year-old children.Methods The study included 144 caries-free children aged 34-38 months.All participants underwent clinical examination and full-mouth supragingival plaque collection.Survey of children's oral health behaviors involving feeding habits and oral health care was also taken from children' s parents of all participants.The children were reexamined 6 and 12 months later.According to the potential changes of caries status in twelve months follow up,all the participants were divided into three groups:caries-free group (caries free children in twelve months follow up),caries at 6-month group(children who were found with caries or cavities fillings at six months review) and caries at 12-month group(children who were caries free at six months but found with caries or cavities fillings at twelve months).Streptococcus mutans (Sm)and Streptococcus sobrinus (Ss) loads were compared among the three groups by real time fluorescence quantitative polymerase chain reaction (FQ-PCR).Results One hundred and thirty children completed twelve months review,the dropout rate was 9.7％ (14/144).At the end of twelve months follow up,the number of children in caries-free group,caries at 6-month group and caries at 12-month group was 58,44 and 28 respectively.The changes of oral behavioral habits in caries-free group,caries at 6-month group and caries at 12-month group during twelve months follow up were not significantly different(P ＞0.05).At baseline,the frequency of sweets consumption and eating sweets before sleeping in caries-free group was significantly lower than that in caries at 6-month group and caries at 12-month group (P ＜ 0.001).At baseline,the quantity of Sm and Ss in caries at 6-month group [copy number of Sm:(6.33 ± 2.21) × 103,copy number of Ss:(1.99 ±0.45) × 103] was significantly higher than that in the caries-free group [copy number of Sm:(5.81 ± 2.43) × 103,copy number of Ss:(1.34 ± 0.53) × 103] (P ＜ 0.05).There was no significant difference in the quantity of Sm and Ss in the caries-free group and caries at 12-month group(P ＞ 0.05).At six months,the quantity of Sm and Ss in caries at 12-month group was significantly higher than that in the caries-free group although both groups of children were caries-free at six months (P ＜ 0.05).Conclusions The quantity of Sm and Ss increased six months before the caries onset in three-year-old children.High frequency sweets consumption and eating sweets before sleeping were important susceptibility factors for caries onset in the future.