BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

OBJECTIVE To analyze the components migrating to blood and metabolites of Polygonum cuspidatum in rats with acute gouty arthritis （AGA）. METHODS SD rats were randomly divided into blank group， model group and P. cuspidatum group （10 g/kg， by raw material）， with 6 rats in each group. Except for blank group， AGA model was induced in the remaining groups by injecting potassium oxonate and sodium urate； meanwhile， they were administered corresponding drug solutions or water intragastrically， once a day， for 10 consecutive days. The histopathological morphology of the knee joint tissues in rats was observed；rat serum samples were collected， and the components migrating to blood and metabolites of P. cuspidatum were analyzed by using UPLC-Q-Exactive-Orbitrap-MS. RESULTS Following the intervention with P. cuspidatum， the histopathological morphology of the knee joint synovial tissue in AGA rats showed significant improvement， with reduced inflammatory cell infiltration and hyperplasia， and the preservation of the honeycomb-like structure integrity. In both positive and negative ion modes， a total of 67 chemical components were detected in the serum of rats from P. cuspidatum group， including 25 prototype components and 42 metabolites. The involved compound types encompassed stilbenes， anthraquinones， naphthols， and flavonoids， among others. The metabolic reactions identified included methylation， acetylation， sulfation， and glucuronidation. Notably， compounds such as polydatin， resveratrol and emodin were capable of entering the bloodstream in their prototype forms and undergoing in vivo metabolism. CONCLUSIONS Compounds such as polydatin， resveratrol and emodin are likely to be the active components responsible for the anti-AGA effects of P. cuspidatum.

ObjectiveTo investigate the infection characteristics of respiratory syncytial virus (RSV) in children with acute respiratory tract infection (ARI) in Pudong New Area, Shanghai, from 2013 to 2023, so as to provide an evidence for the prevention and control of RSV in Shanghai. MethodsChildren who sought medical care at sentinel healthcare facilities in Pudong New Area, Shanghai, between January 2013 and December 2023 and met the case definition of ARI were included in the study. Nasopharyngeal swab samples were collected and tested for viral pathogens using real-time fluorescene PCR, and the clinical information of whom was collected simultaneously. ResultsA total of 4 980 children were included in the ARI surveillance, among whom 231 tested positive for RSV, with an overall detection rate of 4.64%. Of these, 106 cases were type A and 125 were type B. From 2013 to 2023, the detection rate of RSV in children showed an overall trend of initial increase followed by a decline, with higher detection rates in autumn and winter and lower rates in spring and summer. The RSV detection rate gradually decreased with age, with the highest rate observed in children <1 year old, accounting for 16.33% (80/490) of RSV-detection cases. Cough was the most common clinical symptom. Among the RSV-positive cases, 36 involved co-infection with another virus, 6 co-infected with three viruses, and 1 with mixed infection of four viruses. The most frequent co-infection was RSV and human coronavirus. ConclusionChildren under 1 year of age are more susceptible to RSV infection, with cough being the predominant symptom. RSV infection in Pudong New Area, Shanghai, mainly occurs in winter. Targeted prevention and control measures should be taken for children under 1 year old during the winter season to reduce the risk of both RSV infection and co-infection with human coronavirus and influenza virus.

Acupuncture-moxibustion therapy has been known to ameliorate the symptoms of functional gastrointestinal disorders (FGIDs), although its mechanism remains unclear. The paper reviews the articles on acupuncture-moxibustion therapy for FGIDs in recent 5 years, and it is revealed that acupuncture-moxibustion therapy can alleviate FGIDs symptoms through regulating gastrointestinal motility, modulating visceral hypersensitivity, improving the impaired gastric-duodenal mucosal barrier and inflammation, balancing intestinal microbiota, and adjusting the gut-brain axis. Currently, the molecular mechanism of acupuncture-moxibustion therapy remains unknown for FGIDs, the specific disease target is not identified, and the interaction among various molecules is not elucidated adequately. The researches in the future should employ advanced technologies and methodologies to comprehensively and deeply explore and clarify the mechanism of acupuncture- moxibustion therapy for FGIDs.
Humans ; Moxibustion ; Acupuncture Therapy ; Gastrointestinal Diseases/microbiology* ; Animals

Abnormal accumulation of collagen fibrils is a hallmark feature of oral submucous fibrosis (OSF). However, the precise characteristics and underlying mechanisms remain unclear, impeding the advancement of potential therapeutic approaches. Here, we observed that collagen I, the main component of the extracellular matrix, first accumulated in the lamina propria and subsequently in the submucosa of OSF specimens as the disease progressed. Using RNA-seq and Immunofluorescence in OSF specimens, we screened the cartilage oligomeric matrix protein (COMP) responsible for the abnormal collagen accumulation. Genetic COMP deficiency reduced arecoline-stimulated collagen I deposition significantly in vivo. In comparison, both COMP and collagen I were upregulated under arecoline stimulation in wild-type mice. Human oral buccal mucosal fibroblasts (hBMFs) also exhibited increased secretion of COMP and collagen I after stimulation in vitro. COMP knockdown in hBMFs downregulates arecoline-stimulated collagen I secretion. We further demonstrated that hBMFs present heterogeneous responses to arecoline stimulation, of which COMP-positive fibroblasts secrete more collagen I. Since COMP is a molecular bridge with Fibril-associated collagens with Interrupted Triple helices (FACIT) in the collagen network, we further screened and identified collagen XIV, a FACIT member, co-localizing with both COMP and collagen I. Collagen XIV expression increased under arecoline stimulation in wild-type mice, whereas it was hardly expressed in the Comp^-/- mice, even with under stimulation. In summary, we found that COMP may mediates abnormal collagen I deposition by functions with collagen XIV during the progression of OSF, suggesting its potential to be targeted in treating OSF.
Oral Submucous Fibrosis/pathology* ; Cartilage Oligomeric Matrix Protein/genetics* ; Animals ; Mice ; Humans ; Fibroblasts/metabolism* ; Collagen Type I/metabolism* ; Arecoline/pharmacology* ; Mouth Mucosa/metabolism* ; Cells, Cultured ; Fluorescent Antibody Technique

Objective To explore the clinical characteristics of patients with drug-induced liver injury(DILI),so as to provide references for its diagnosis and treatment.Methods The clinical data of inpatients diagnosed as DILI in The Third Affiliated Hospital of Naval Medical University(Second Military Medical University),from Jan.2017 to Dec.2021 were retrospectively analyzed,including basic information,underlying diseases,drug use history,clinical manifestations,laboratory indexes,severity and prognosis of DILI.Results Among 145 patients with DILI,112 cases(77.24％)were hepatocellular type,25 cases(17.24％)were cholestatic type,and 8 cases(5.52％)were mixed type.The types of drugs causing DILI mainly included traditional Chinese medicine,proprietary Chinese medicine and anti-infective drugs,and the proportions were 48.72％(76/156),16.03％(25/156),and 10.26％(16/156),respectively.The common clinical manifestations of DILI patients were jaundice(76.55％),poor appetite(52.41％),and fatigue(49.66％).The levels of alanine transaminase(ALT),aspartate transaminase,alkaline phosphatase(ALP),total bilirubin(TBil),γ-glutamyl transferase and albumin(ALB),as well as the length of hospital stay and severity distribution were significantly different among different types of liver injury(all P＜0.05).The levels of ALT and ALB in the good prognosis group were significantly higher than those in the poor prognosis group,while the levels of TBil and international normalized ratio in the good prognosis group were significantly lower than those in the poor prognosis group(all P＜0.05).Multivariate analysis showed that INR was an independent predictor of the prognosis of DILI(P＜0.05).Conclusion Serum biochemistry indicators can help to identify the clinical classification and prognosis of DILI.Traditional Chinese medicine,proprietary Chinese medicine and other drugs can cause DILI.Medical staff should pay attention to it and strengthen public health education.

Objective To construct the prediction model of perineural invasion(PNI)in gallbladder carcinoma(GBC)based on preoperative enhanced CT image features and evaluate its prediction efficiency.Methods The clinical,imaging and pathological data of 180 GBC patients undergoing radical operation were retrospectively analyzed.They were divided into positive and negative groups according to the presence or absence of PNI.Preoperative enhanced CT imaging features(including presence of gallstones,imaging hepatic invasion,vascular invasion,T-stage,and hilar or retroperitoneal lymph node metastases)were evaluated by two radiologists.Independent sample t-test,Mann Whitney U test,and X2 test were used to compare the correlation between CT signs and PNI.Logistics regression analysis was used to screen independent risk factors and establish the prediction model formula.ROC curve was used to evaluate the prediction efficiency of the prediction model and the corresponding area under the curve(AUC)was calculated.Hosmer-Lemeshow goodness of fit test was used to verify the prediction model.Results Unifactorial analysis showed that CA199,CA125,imaging hepatic invasion,vascular invasion(hepatic artery or portal vein),T-stage,and hilar or retroperitoneal lymph node metastasis were correlated with nerve invasion(P＜0.05).Logistics multi-factor analysis results showed that CA199,imaging vascular invasion(hepatic artery or portal vein),and imaging T stage were independent risk factors for PNI.Based on the above independent risk factors,a prediction model formula was established and ROC curve was drawn,with an AUC of 0.807(95％CI:0.734～0.879),sensitivity of 0.792,specificity of 0.697,and the chi-square value of Hosmer-Lemeshow goodness of fit test of 0.594(P=0.997),indicating that the predicted value of the model was close to the actual value.Conclusion Combining CA199,imaging vascular invasion,T-stage,and other preoperative clinically-enhanced CT features to establish a prediction model can effectively predict postoperative PNI of GBC.

Objective To investigate the clinical application of 3D printed bolus with specific density in breast cancer radiotherapy,and to evaluate its effects on dose distribution and positioning.Methods Forty post-mastectomy patients undergoing intensity-modulated radiotherapy were randomly enrolled for 3D printed bolus(n=20)and conventional bolus(n=20),and all patients were fixed in the supine position using styrofoam.Conventional positioning was performed based on in-room lasers and body markers,with daily Catalyst HD optical surface monitoring combined with weekly CBCT verification.The absolute dose,patients'skin surface dose,surgical incision,planned field,target area doses(VCTV50Gy,VPTV50Gy)and organs-at-risk doses in patients with different boluses were recorded,and the conformity index and homogeneity index were calculated,and the setup errors using CBCT and Catalyst HD were also analyzed.Results The difference in absolute dose between different boluses was trivial,but the skin surface dose with 3D printed bolus was significantly higher than with conventional bolus[(54.83±0.44)Gyvs(54.43±0.51)Gy,P<0.05].Patients with 3D printed boluses had a higher conformity index than with conventional boluses(0.69±0.04 vs 0.65±0.02).For different boluses,there was no significant difference in VCTV50 Gy,while the VPTV50 Gy and organs-at-risk doses were lower in those with 3D printed bolus than conventional boluses(P<0.05),with heart Vmean of 9.68%±3.24%vs11.43%±3.60%.In patients with 3D printed boluses,both planned field arrangement and surgical incision affected the target doses,and the doses of the target area without an internal breast wrap was greater than those with internal breast wrap(P<0.05).When the field was not wrapped around the internal breast,the surgical incisions only affected VPTV50 Gy,and the VPTV50 Gy was greater with the transverse fusiform incision than with the oblique vertical incision(P<0.05),which were 95.58%±0.51%vs95.44%±0.71%.The optical monitoring accuracies with different boluses differed only in the left-right direction(P<0.05),with(0.08±0.57)cm and(-0.15±0.46)cm for 3D printed and conventional boluses.Conclusion Compared with conventional bolus,3D printed bolus can improve dose distribution and optical monitoring accuracy.The surgical incision and planned field arrangement under 3D-printed bolus would exert effects on target doses.

AIM:To observe the intervention ef-fect of Chinese medicine Kangzhen Zhijing spas-modic decoction Ⅰ on the progression of Parkin-son's disease in mice,and to explore the potential mechanism of neuroprotection.METHODS:Thirty-six C57BL/6 mice were randomly divided into con-trol group,model group,drug group and positive drug group.In the model group,the drug adminis-tration group and the positive drug group,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(30 mg/kg)was injected intraperitoneally for 5 days to establish the mouse model.The control group was given the same amount of normal saline,the drug administration group was given 1.25 mg/kg,2.5 mg/kg,5 mg/kg dose of Chinese medicine Kang-zhen Zhijing spasmodic DecoctionⅠby gavage,and the positive drug group was given 75 mg/kg Madopar by gavage.Behavioral tests were per-formed on the second day after the administration in each group.Immunopositive cells of Tyrosine hy-droxylase(TH),Amyloid precursor protein(APP),α-synuclein(α-syn)and solute carrier family 6 mem-ber 11(SLC6A11)were detected by immunohisto-chemistry.The protein expressions of TH,APP,α-syn and SLC6A11 in each group were detected by Western blot.RESULTS:It could significantly im-prove the weight loss of mice in the model group,alleviate the decline of autonomic activity in open field test and the decline of coordination ability in pole test and suspension test.In the reverse immu-nohistochemistry and Western Blot experiments,the expressions of TH and SLC6A11 in the brain of the Parkinson's model group were significantly de-creased,and the expressions of APP and α-syn were significantly increased.CONCLUSION:Kang-zhen Zhijing spasmodic decoctionⅠcan significantly improve the behavioral performance of Parkinson's disease mice and effectively improve the reduction of neuronal transmitters.

Eyes are an important part of facial morphology. The study of eye morphology is of great value in exploring human growth and establishing eye database. Its shape and size are influenced by factors such as gender, age, and ethnic group. The related literature on eye morphology mainly includes the following aspects: gender, age, and ethnic differences of eye morphological variation; factors affecting eye shape variation; eyelid shape; eye symmetry research; eye morphology and epicanthus; measurement of eye shape related parameters; related application of eye morphology, etc. By sorting out and summarizing the research data and conclusion of related literature, this article briefly outlines the research on eye morphology and the measurement method of eye parameters, furthermore, it gives a brief review and outlook on the research of eye morphology in China.