ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

OBJECTIVE: To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG). METHODS: Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People's Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes (MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People's Hospital Affiliated to Jiangsu University (Ethics No. 20150083). RESULTS: m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P < 0.05). RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P < 0.000 5). CONCLUSION These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.
Humans ; RNA, Messenger/metabolism* ; Adenocarcinoma/pathology* ; Esophagogastric Junction/metabolism* ; Esophageal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Middle Aged ; DNA Methylation ; Methyltransferases/metabolism* ; Stomach Neoplasms/genetics*

OBJECTIVE: To analyze the clinical characteristics of a patient with Short rib-polydactyly syndrome type 6 (SRTD6) with long-term misdiagnosis, and improve its clinical recognition by reviewing the relevant literature. METHODS: A patient presented at the Children's Hospital Affiliated to Zhejiang University School of Medicine on August 19, 2024 for the discovery of liver dysfunction for 13 years and vision loss for 9 years was selected as the study subject. Her medical history, clinical data, laboratory findings and results of imaging examination were collected. High-throughput sequencing was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Hospital (Ethics No.: 2021-IRB-292). RESULTS: The patient had long-term unexplained liver dysfunction, vision loss, and growth delay. Blood acylcarnitine and urinary organic acid analysis have failed to found any abnormality. Previous genetic testing revealed a homozygous c.203A>C (p.Glu68Ala) missense variant in the ETFDH gene, leading to a misdiagnosis of various acyl-CoA dehydrogenase deficiencies. However, treatment with high-dose vitamin B₂ showed a poor effect. Physical examination revealed small hands, short and stubby fingers, and a narrow chest. Medical imaging showed shortened bilateral ribs, a narrowed chest, and short, thick metacarpals. High-throughput sequencing has detected a pathogenic homozygous c.1957C>T (p.R653*) nonsense variant in the NEK1 gene, confirming the diagnosis of SRTD6. CONCLUSION SRTD6 is characterized by rib and sternum dysplasia as the primary skeletal deformities, which is often accompanied by multi-organ impairment. Genetic testing can facilitate the precise diagnosis.
Humans ; Female ; Diagnostic Errors ; Short Rib-Polydactyly Syndrome/diagnosis* ; High-Throughput Nucleotide Sequencing

Objective To analyze the willingness and influencing factors of doctors in Beijing public hospitals to set up clinics in the community,and to provide scientific basis for promoting quality health technicians to go down to the grassroots and realize hierarchical diagnosis and treatment.Methods Doctors from 6 specialized hospita ls and 3 general hospitals in Beijing were selected as subjects for questionnaire survey.By stratified sampling,a questionnaire survey was conducted on 518 doctors from 9 public hospitals in Beijing through stratified sampling method.Descriptive analysis,rank sum test and ordered logistic regression were used to explore doctors'willingness to open clinics and its influencing factors.Results In all survey respondents,212(40.93%)physicians were very or somewhat willing to open a clinic in the community,physicians with higher benefit perception,and greater willingness to publicize relevant policies were more willing to set up clinics.Conclusion Opening of clinics by doctors in public hospitals is affected by perceived benefits and willingness to advocate policies.It is suggested to further improve relevant systems and policies,reduce the risk of doctors opening clinics,and promote doctors in public hospitals to open clinics in communities,so as to realize the sinking of high-quality health human resources to the grassroots.

OBJECTIVE To retrospectively analyze the prevalence of ventilator-associated pneumonia(VAP)in Gansu Province in 2023 so as to provide scientific bases for formulating and optimizing prevention and control strategies for VAP in the health care institutions of the province.METHODS The data regarding to VAP of 2023 were collected from the regional surveillance platform of Gansu Province Nosocomial Infection Management Quali-ty Control Center.The influencing factors for the VAP were assessed by means of Poisson regression model.RESULTS In 2023,the median incidence of VAP was 3.51 ‰ among the 93 hospitals in Gansu Province.There was significant difference in the incidence of VAP among the different regions,levels and types of hospitals(P＜0.05).The length of hospital stay and ventilator treatment duration of the tertiary hospitals were 3458(1904,6770)days and 1 274(740,2040)days,respectively,higher than those of the secondary hospitals;the incidence of VAP was 4.89(2.82,7.40)‰ in the tertiary hospitals,higher than that in the secondary hospitals(all P＜0.05).The incidence of VAP of the general hospitals was 3.94(2.66,6.92)‰,higher than 2.06(1.03,3.27)‰ of the specialized hospitals(P＜0.001).With the respect to the regional factor,Qingyang City,Baiyin City,Dingxi City and Linxia City were at lower risk of VAP than Lanzhou City after the related factors were controlled through Poisson regression analysis(P＜0.05),while Zhangye City and Jiayuguan City were at higher risk of VAP(P＜0.05).The analysis of seasonal factors showed that the incidence of VAP presented seasonal fluctuation,the inci-dence of VAP was higher in the second and fourth quarters;however,there was no significant difference in the risk of VAP among the quarters.CONCLUSIONS The incidence of VAP is decreased in Gansu Province in 2023 as compared with that in previous years,however,there is certain difference among the different regions.The inci-dence rates of VAP are relatively high in the tertiary hospitals and the general hospitals.It is necessary to strengthen the surveillance in related areas and take active prevention and control measures,so as to reduce the in-cidence of VAP.

Objective:To explore the prominent manifestations and internal associations of the overuse of short-form videos,inattention,and school refusal behavior in junior high school students.Methods:A survey was conducted among 1 106 junior high school students,utilizing the Short-form Video APP Overuse Scale,the Inatten-tion subscale of the Swanson,Nolan,and Pelham Rating Scale(SNAP-Ⅳ),and the School Refusal Behavior Ques-tionnaire to assess the extent of short-form video overuse,inattention,and school refusal behavior.By using the R language for network analysis,the core nodes of individual networks and the bridge nodes connecting the combined networks were analyzed,and the structural differences in networks across genders and grades were compared.Re-sults:The core nodes of the network pertaining to overuse of short-form video,inattention,and school refusal behav-ior were"Using short videos enhances connection with others"(expected influence value=1.03),"easily distract-ed"(expected influence value=1.99),and"school alienation"(expected influence value=0.83).The bridge nodes in the combined network were"defiant behavior"(bridge expected influence value=0.69)and"difficulty sustaining mental activities"(bridge expected influence value=0.47).Analysis of network structure differences i-dentified that the core nodes within the combined networks of the first,second,and third grades of junior high school students were respectively"prioritizing short videos over other activities","defiant behavior",and"academic aptitude".Conclusion:Junior high school students exhibiting overuse of short videos,inattention,or school refusal behavior are characterized by enhanced social connectivity through platforms such as short video apps,a propensity for distraction,and feelings of school alienation,respectively.When these three behaviors coexist,the most salient related factor is oppositional behavior,coupled with difficulties in sustaining cognitive tasks and maintaining con-centration.

The method of promoting blood circulation and removing blood stasis holds a significant position in the theoretical frame-work of traditional Chinese medicine(TCM)for cancer treatment.However,the impact of blood-activating and stasis-eliminating herbs on tumor metastasis remains a subject of clinical uncertainty,which has drawn considerable attention to research on their effects.Based on TCM's understanding of the etiology and pathogenesis of tumors,this article elaborates on the molecular mechanisms through which blood-activating and stasis-eliminating Chinese herbs and their active components influence tumor metastasis.This in-cludes their roles in affecting tumor angiogenesis,inducing normalization of tumor blood vessels,and interfering with the Warburg effect in tumor cells.The findings provide a scientific basis for the anti-tumor theory of the blood-activating and stasis-eliminating ap-proach.

Objective To explore surgical treatment efficacy for PAES.Methods A retrospective analysis was done on 12 PAES patients'surgery in our hospital from March 2018 to December 2023.Surgical plans included double popliteal artery exploration and repositioning with tendon transplantation,popliteal artery and vein release plus arterial thrombus removal,popliteal fossa exploration with popliteal artery release,and autologous vein patch angioplasty plus abnormal muscle bundle resection.Results Follow-up was 3 months to 5 years.11 patients had good affected limb skin temperature and blood supply,no symptom recurrence.One patient had left lower limb skin temperature decrease and pallor 2 years post-op(diagnosed as left popliteal fossa traumatic neuroma compressing popliteal artery),with blood supply restored after tumor removal.Conclusion Open surgery(tendon transplantation,vein patch)for PAES is effective.