ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

Objective To investigate the application value of rice bag in 1.5T MR imaging of maxillofacial frequency selective saturated fat suppression(FS)sequence.Methods Forty-one patients with maxillofacial MR examination were collected.Rapid fast spin echo(FSE)FS T2 routine scan and rice bag FSE FS T2 special scan were used to evaluate and analyze the sequence images of the two kinds by two experienced associate chief physicians in the department according to the Likert 7-point scoring system.The evaluation included FS,magnetic sensitive artifact,motion artifact,and overall image quality.Wilcoxon sign rank sum test was used to analyze the difference of image quality scores,and Kappa consistency test was used to analyze the correlation between two viewers.Results All the 41 patients completed the examination,and the FSE FS T2 plus rice bag group had significantly higher FS,magnetic sensitive artifact,motion artifact and overall image quality than the conventional FSE FS T2 group,with statistical significance(P<0.01).Kappa consistency was good in correlation analysis between the two viewers(Kappa value=0.737-0.877,P<0.01).Conclusion The application of rice bag in the 1.5T MR maxillofacial FS sequence scan has the advantages of good image quality,good FS effect and few artifacts,which can better display the maxillofacial anatomical structure and lesions,and has important clinical application value for the diagnosis of maxillofacial diseases.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA)).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory effect of hucMSCs-exolet-7a-5p mimic on CVB3-induced ferroptosis was higher than that of hucMSCs-exomimicNC(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe2+increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Objective: To examine the relationship between 24 hour movement behavior and physical fitness of pupils by using compositional analyses, so as to provide a theoretical basis for physical activity promotion and physical fitness improvement. Methods: By random cluster sampling method, 120 students of grade 4 and 5 from the Second Experimental Primary School of Yingze District of Taiyuan were selected. Physical fitness was evaluated by the indicators of the Protocol of National Physical Training Standard and 20 meter shuttle run. The movement behavior was measured by accelerometer. The relationship between each behavior and physical fitness was analysed by component multiple linear regression, and the effect of replacement of components on physical fitness was discussed. Results: Girls 1minute situps were lower than boys（24.79±7.77，28.21±6.52），and sitting forward flexion was higher than boys[9.00（5.00，14.00），5.20（1.00，9.75）cm]（ t/Z =2.60，-3.15， P ＜0.05）. Boys showed higher light physical activity(LPA), moderate to vigorous physical activity(MVPA) and lower sedentary behavior(SB), while girls showed lower LPA, MVPA and higher SB. MVPA was positively correlated with the performance of 30 second rope skipping and 20 meter shuttle run ( β= 13.19, 7.90, P <0.05). Sleep(SLP), SB, and LPA were not significantly correlated with physical fitness. After re allocating 10 min MVPA to SB and SLP，the performance of 30 second rope skipping and 20 meter shuttle run increased by 2.25，2.28 and 1.28 ,1.34 times，respectively，while significantly decreased after reverse reallocation ( P <0.05). MVPA replaced LPA，the 20 meter shuttle run performance increased 1.46 times，while decreased significantly in reverses ( P <0.05). Conclusion MVPA is positively correlated with the speed and endurance of pupils. There are gender differences in movement behavior patterns and physical fitness. Children, especially girls, should be encouraged to raise exercise awareness and increase PA, especially MVPA.

Objective:To explore the risk factors of acute kidney injury(stage 3)developed within 48 hours in elderly patients with sepsis, and to use them to develop a risk prediction model and then evaluate and externally validate the model.Methods:Clinical data of all elderly patients(age≥ 60 years)with sepsis in the intensive care medicine information database(MIMIC-Ⅳ v1.0)were extracted.Independent risk factors were determined by multivariate logistic regression analysis.A risk prediction model was constructed, a nomogram was drawn, and the receiver operating characteristic curve(ROC)and the Hosmer-Lemeshow(H-L)test were used to evaluate the model's prediction accuracy and R-squared.Clinical data of elderly patients(age≥ 60 years)with sepsis admitted to the Department of Critical Care Medicine of the Second People's Hospital of Hefei from May 2019 to October 2021 were retrospectively collected and fed into the prediction model to conduct external validation.Results:A total of 1 977 elderly patients with sepsis were screened out from the MIMIC-IV database and included in the training set, of whom, 544 developed AKI-stage 3 within 48 hours.Univariate analysis was performed for factors that might be associated with acute kidney injury in elderly patients with sepsis.Compared with the normal group that did not progress to AKI stage 3, there were statistically significant differences in 28 indicators, such as the duration of ICU stay, intravenous fluid intake in 24 hours, and use of vasoactive drugs[5(3, 9)d vs.7(4, 12)d; 2.05(1.17, 3.27)ml·kg -1·h -1vs.2.37(1.47, 4.10)ml·kg -1·h -1; 761(53.11%) vs.375(68.93%), P<0.001]. Based on the results of multivariate logistic regression analysis, a prediction model was finally constructed with 9 variables: albumin( OR=0.983, 95% CI: 0.966-0.999, P=0.040), aspartate transaminase( OR=1.000, 95% CI: 1.000-1.000, P<0.001), APTT( OR=1.005, 95% CI: 1.001-1.009, P=0.028), total bilirubin( OR=1.003, 95% CI: 1.001-1.004, P=0.001), serum creatinine( OR=1.005, 95% CI: 1.004~1.007, P<0.001), Charlson score( OR=1.117, 95% CI: 1.061-1.177, P<0.001), intravenous fluid intake in 24 hours( OR=1.101, 95% CI: 1.034-1.173, P=0.003), weight( OR=1.023, 95% CI: 1.018-1.029, P<0.001), and mechanical ventilation( OR=2.412, 95% CI: 1.843-3.157, P<0.001). Then a nomogram was generated.The area under the ROC curve(AUC)of the prediction model was 0.755(95% CI: 0.731-0.780), and the H-L test was conducted( χ2=10.89, P=0.208>0.05), indicating a good fit.Data from 102 elderly patients were included in the validation set, with 27 cases that had developed AKI-stage3 within 48 hours, and were fed into the prediction model, with an AUC of 0.778(95% CI: 0.676-0.880)and χ2=3.72 and P=0.882>0.05 from the H-L test, consistent with the results of the training set. Conclusions:The model has some predictive value for acute kidney injury in elderly patients with sepsis.

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.