Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO₂) (200 mg·mL^-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO₂ group, (2) SiO₂+negative control siRNA (siRNA-NC) group and SiO₂+Smurf2 gene silencing (si-Smurf2) group, (3) SiO₂+solvent (DMSO) group and SiO₂+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO₂+miR-NC group and SiO₂+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO₂-induced MLE-12 cells, compared to the control group, the SiO₂-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO₂, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO₂ group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To analyze the clinical characteristics and treatments of children with myocarditis,and to investigate the relation-ship between arrhythmia and prognosis.Methods A total of 244 patients diagnosed with myocarditis from January 2012 to December 2023 were included and retrospectively analyzed.The patients were divided into three groups:fulminant myocarditis(FMC),myocarditis(MC),and suspected myocarditis(SMC).The data included the clinical characteristics at disease onset,the treatment,and the relationship between different arrhythmias and the prognosis among the three groups.Results Among the 244 children with FMC/MC/SMC,132/244(54.1％)developed arrhythmia,ventricular arrhythmia was observed in 83/132(62.9％),and 86/105(81.9％)showed no persistent arrhythmia.The proportion of children in the FMC group who presented with palpitations,cardio-cerebral syndrome,cardiogenic shock,cardiac insufficiency,and death was significantly higher than that in the MC and SMC groups(P＜0.01).Five children with third-degree(Ⅲ°)atrioventricular block(AVB)recovered after controlling their ventricular rate without a temporary pacemaker.Conclusion Most children with FMC/MC/SMC have different types of arrhythmias,of which ventricular arrhythmias are the most common,and rarely persist.FMC has severe clinical symptoms and the highest mortality rate.Ventricular tachycardia usually occurs during the administration of vaso-active drugs in patients with Ⅲ ° AVB;if the ventricular rate can be controlled promptly,these patients have a good prognosis.

Radiation-induced heart disease(RIHD)is a severe complication in patients with thoracic cancer undergoing radiotherapy,with important impacts on long-term survival among cancer survivors.There is an urgent need to investigate the pathogenesis of RIHD and to develop effective therapeutic agents,and the establishment of high-quality RIHD animal models is pivotal to addressing these issues.This review summarizes the critical factors to consider in establishing RIHD animal models,including species selection,radiation type,dosage,fractionation,and target fields,and modeling timeline,along with the evaluation method and success criteria.We also consider the potential pathogenic mechanisms underlying RIHD,including DNA damage,oxidative stress,inflammatory responses,mitochondrial dysfunction,renin-angiotensin-aldosterone system activation,and myocardial fibrosis,as well as their interrelationships.These insights provide a comprehensive reference framework for constructing RIHD animal models and advancing mechanistic investigations into this condition.

Objective To analyze the clinical characteristics and treatments of children with myocarditis,and to investigate the relation-ship between arrhythmia and prognosis.Methods A total of 244 patients diagnosed with myocarditis from January 2012 to December 2023 were included and retrospectively analyzed.The patients were divided into three groups:fulminant myocarditis(FMC),myocarditis(MC),and suspected myocarditis(SMC).The data included the clinical characteristics at disease onset,the treatment,and the relationship between different arrhythmias and the prognosis among the three groups.Results Among the 244 children with FMC/MC/SMC,132/244(54.1％)developed arrhythmia,ventricular arrhythmia was observed in 83/132(62.9％),and 86/105(81.9％)showed no persistent arrhythmia.The proportion of children in the FMC group who presented with palpitations,cardio-cerebral syndrome,cardiogenic shock,cardiac insufficiency,and death was significantly higher than that in the MC and SMC groups(P＜0.01).Five children with third-degree(Ⅲ°)atrioventricular block(AVB)recovered after controlling their ventricular rate without a temporary pacemaker.Conclusion Most children with FMC/MC/SMC have different types of arrhythmias,of which ventricular arrhythmias are the most common,and rarely persist.FMC has severe clinical symptoms and the highest mortality rate.Ventricular tachycardia usually occurs during the administration of vaso-active drugs in patients with Ⅲ ° AVB;if the ventricular rate can be controlled promptly,these patients have a good prognosis.

Radiation-induced heart disease(RIHD)is a severe complication in patients with thoracic cancer undergoing radiotherapy,with important impacts on long-term survival among cancer survivors.There is an urgent need to investigate the pathogenesis of RIHD and to develop effective therapeutic agents,and the establishment of high-quality RIHD animal models is pivotal to addressing these issues.This review summarizes the critical factors to consider in establishing RIHD animal models,including species selection,radiation type,dosage,fractionation,and target fields,and modeling timeline,along with the evaluation method and success criteria.We also consider the potential pathogenic mechanisms underlying RIHD,including DNA damage,oxidative stress,inflammatory responses,mitochondrial dysfunction,renin-angiotensin-aldosterone system activation,and myocardial fibrosis,as well as their interrelationships.These insights provide a comprehensive reference framework for constructing RIHD animal models and advancing mechanistic investigations into this condition.

Objective:To establish a similarity measurement model for patients with dentofacial deformity based on 3D craniofacial features and to validate the similarity results with quantifying subjec-tive expert scoring.Methods:In the study,52 cases of patients with skeletal Class Ⅲ malocclusions who underwent bimaxillary surgery and preoperative orthodontic treatment at Peking University School and Hospital of Stomatology from January 2020 to December 2022,including 26 males and 26 females,were selected and divided into 2 groups by sex.One patient in each group was randomly selected as a reference sample,and the others were set as test samples.Three senior surgeons rated the similarity scores between the test samples and the reference sample.Similarity scores ranged from 1 to 10,where 1 was completely different,and 10 was exactly the same.Scores larger than 7.5 was considered as clinical-ly similar.Preoperative cone beam computed tomography(CBCT)and 3D facial images of the patients were collected.The three-dimensional hard and soft tissue features,including distances,angles and 3D point cloud features were extracted.The similarity measurement model was then established to fit with the experts'similarity scoring by feature selection algorithm and linear regression model.To verify the relia-bility of the model,14 new patients were selected and input to similarity measurement model for finding similar cases.The similarity scoring of these similar cases were rated by experts,and used to evaluate the reliability of the model.Results:The similarity metric models indicated that the features of the middle and lower craniofacial features were the main features to influence the craniofacial similarity.The main features that were related to the expert's similarity scoring included distance of anterior nasal spine-menton(ANS-Me),distance of right upper canion point-Frankfurt horizontal plane(U3RH),distance of left superior point of the condyle-left gonion(CoL-GoL),distance of left gonion-menton(CoL-Me),dis-tance of pogonion-midsagittal plane(Pog-MSP),distance of right alar base-left alar base(AlR-AlL),angle of pronasale-soft tissue pogonion-labrale inferius(Pn-Pog'-Li),distance of trichion-right tragus(Tri-TraR),distance of left exocanthion-left alar base(ExL-AlL),lower 1/3 of skeletal face,middle and lower 2/3 of skeletal face and upper lip region of soft tissue.Fourteen new patients were chosen to evaluate the model.The similar cases selected by the model had an average experts'similarity scoring of 7.627±0.711,which was not significantly different with 7.5.Conclusion:The similarity measurement model established by this model could find the similar cases which highly matched experts'subjective simi-larity scoring.The study could be further used for similar cases retrieval in skeletal Ⅲ malocclusion patients.

Objective:To investigate the popularization of non-iodized salt among residents in water-borne high iodine areas and the iodine nutrition status of key populations in Shandong Province.Methods:In 2021, monitoring was conducted on a county-by-county basis in 47 counties (cities, districts, hereinafter referred to as counties) in 9 cities of Shandong Province, in accordance with the newly designated high iodine areas in the "Definition of Water Source High Iodine Areas and High Iodine Disease Areas" (GB/T 19380-2016) and historical high iodine areas. In each monitoring county, administrative villages with a median water iodine level greater than 100 μg/L were sorted by water iodine value, and a systematic sampling method was used to select 5 administrative villages as monitoring sites to investigate the water improvement situation and the iodine level of residents' drinking water. Totally 40 non boarding students aged 8 to 10 from one primary school and 20 pregnant women were selected in each village location to collect household edible salt samples and random urine samples for testing salt iodine and urine iodine levels, and the B-ultrasound method was used for thyroid examination in children.Results:A total of 364 high iodine administrative villages had been monitored, all of which had completed water improvement with a water improvement rate of 100.0%. The median iodine content in residential drinking water was 20.3 μg/L, ranging from 0.1 to 869.1 μg/L; and 11 464 edible salt samples were collected from residents' homes, with a non-iodized salt rate of 82.7% (9 481/11 464). A total of 9 197 urine samples from children and 2 335 urine samples from pregnant women were tested, with median urinary iodine levels of 219.0 and 139.0 μg/L, respectively. A total of 9 197 children were examined for thyroid, with 262 cases detected and a goiter rate of 2.8%.Conclusions:The rate of non-iodized salt in high iodine areas of Shandong Province still needs to be improved. Children's iodine nutrition is above the appropriate level, while pregnant women are at an iodine deficiency level.

Objective:To explore the ventilation strategy of using pressure controlled ventilation-volume guaranteed (PCV-VG) mode combined with personalized positive end expiratory pressure (PEEP) during surgery, and its impact on oxygenation function and incidence of postoperative pulmonary complications (PPCs) in patients undergoing brain tumor surgery.Methods:Sixty patients who underwent elective brain tumor surgery at the Linyi People′s Hospital from January 2023 to June 2023 were selected. The patients were randomly divided into PCV-VG ventilation mode group (T group) and volume controlled ventilation (VCV) mode group (C group) using a random number table method, with 30 patients in each group. One patient was excluded from group T due to changes in the condition, and 29 patients were actually included. Group T adopted PCV-VG ventilation mode and searched for the maximum dynamic lung compliance (Cdyn) by titrating PEEP. The PEEP corresponding to the maximum Cdyn value was the optimal PEEP, which was maintained until the end of mechanical ventilation. Group C adopted a ventilation mode of VCV plus 5 cmH 2O fixed value PEEP. All patients underwent arterial blood gas analysis before anesthesia induction (T 1), 15 minutes after setting ventilation mode (T 2), and 15 minutes after extubation (T 3), recording arterial oxygen partial pressure (PaO 2), carbon dioxide partial pressure (PaCO 2), lactate (Lac), and blood glucose (Glu), and calculating oxygenation index (PaO 2/FiO 2). The levels of white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were recorded before and 72 hours after surgery. The incidence of postoperative PPCs at 72 hours was observed. Results:There was a statistically significant difference in the grouping effect and time effect of PaO 2 and PaCO 2 between group C and group T (all P<0.05), while there was no statistically significant difference in the interaction effect (all P>0.05); The differences in grouping effects, time effects, and interaction effects of PaO 2/FiO 2 between group C and group T were statistically significant (all P<0.05); The average value of the optimized PEEP obtained by T-group titration was 7.48 cmH 2O, corresponding to an average platform pressure (Pplat) of 14.90 cmH 2O, and an average value of 53.37 ml/cmH 2O corresponding to the maximum Cdyn value. Compared with the Pplat and Cdyn corresponding to the fixed value of 5 cmH 2O PEEP in Group C, the Pplat corresponding to the optimized PEEP in Group T was lower than that in Group C ( P<0.05), and the Cdyn was higher than that in group C ( P<0.05). The CRP level and incidence of PPCs in group T after 72 hours of surgery were significantly lower than those in group C (all P<0.05). Conclusions:Compared with VCV, the ventilation mode of PCV-VG combined with personalized PEEP can improve intraoperative lung ventilation and oxygenation function in patients with brain tumors, reduce the occurrence of pulmonary inflammation 72 hours after surgery, and lower the incidence of PPCs.

Objective:To investigate the drug resistance status and genomic characterization of Proteus mirabilis (PM) isolated from outpatient cases with diarrhea in Tai′an City and Laizhou City, Shandong Province. Methods:A total of 510 fecal samples were collected from 510 patients with acute diarrhea admitted to 43 sentinel hospitals in Tai′an City and Laizhou City, Shandong Province, between January 2021 and December 2022. The samples were cultured and isolated to identify Proteus spp. by direct inoculation, the drug susceptibility testing was performed by microbroth dilution method, and resistance genes and virulence genes were obtained by whole genome sequencing and bioinformatic analysis, thereby revealing the genetic environment surrounding the blaOXA-1 and blaCTX-M-65 genes. Single nucleotide polymorphism (SNP) analysis and core genome multilocus sequence typing (cgMLST) were conducted on the current strains and 100 PM isolates downloaded from the National Center for Biotechnology Information (NCBI) database via customizable methods utilizing RidomSeqSphere+ software, with the objective of exploring the phylogenetic relationships among the strains. Results:A total of 35 strains of Proteus were isolated from 510 fecal samples, including 31 strains of PM with a detection rate of 6.08% (31/510) and four strains of Proteus vulgaris.The multidrug resistance rate of PM was 100.00% (31/31).The 35 isolates carried a total of 43 resistance genotypes.Thirteen strains of PM carried blaOXA-1, six strains carried both blaOXA-1 and blaCTX-M-65, and 15 PM strains carried at least 15 antibiotic resistance genes (ARGs). The virulence genes included ureA, mrpA, ZapA, hpmA and so on. blaOXA-1 and blaCTX-M-65 genes were surrounded by mobile elements such as Tn3, ISL3 and IS6. cgMLST showed consistency with the SNP clustering results. Isolate 2022LZ41 from Laizhou City clustered with isolates 2022TA018, 2022TA017 and 2022TA019 from Tai′an City, with the number of allelic differences ranging from zero to two, and the Laizhou City isolate 2022LZ40 was highly genetically related to strain CRK0056 (human, USA, 2015). Conclusions:PM isolated from patients with diarrhea is multidrug-resistant, carrying many resistance and virulence genes.The presence of mobile genetic elements can lead to horizontal transfer of resistance genes.