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.

Objective To explore the effects of monocular deprivation(MD)on the expression of astrocytes in the superior colliculus,hippocampus,and visual cortex in mice during the critical period of visual development.Methods Eighteen C57BL/6J mice were randomly divided into the normal control group(CON group)and the MD group,with 9 mice in each group.Mice were bred under the 12 h/12 h dark/light conditions.Mice in the CON group received no treat-ment,while mice in the MD group underwent MD of the right eye on postnatal day 27,and the tissue was removed after 7 days.The mRNA and protein expression levels of glial fibrillary acidic protein(GFAP)in the superior colliculus,hippo-campus and visual cortex of mice in the two groups were detected using the real-time reverse transcription quantitative pol-ymerase chain reaction(RT-qPCR)and Western blot,respectively.The number of astrocytes labeled by GFAP and central nervous system specific protein β(S100β)in the superior colliculus,hippocampus and visual cortex of mice in the two groups was detected using the immunofluorescence staining.Results RT-qPCR and Western blot results showed that compared with the CON group,the mRNA and protein expression levels of GFAP in the superior colliculus,hippocampus(CA1,CA3 and dentate gyrus)and visual cortex of mice in the MD group decreased,and the differences were statistically significant(all P＜0.05).The immunofluorescence staining results showed that compared with the CON group,the number of GFAP and S1OOβ co-labeled astrocytes in the superior colliculus,hippocampus(CA1,CA3 and dentate gyrus)and visual cortex of mice in the MD group decreased,and the differences were statistically significant(all P＜0.05).Conclusion MD of mice during the critical period of visual development can result in a decrease in the number of astrocytes in the supe-rior colliculus,hippocampus and visual cortex.

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.

Objective:To investigate Helicobactor pylori (H. pylori) infection status and interfamilial transmission pattern in Zhengzhou area. Methods:A cross-sectional study was conducted from September 2020 to march 2021, among 731 individual from 266 families randomly selected from 9 communities of Zhengzhou area. H. pylori infection status was determined by serum antibody tests, and 13C-urea breath test was performed in the previously eradicated population to clarify the current infection status. The individual and familial infection rate, infection status for couples and children and adolescent were analyzed. Results:Among 731 individuals from 266 families, 397 of them were H. pylori positive. The individual infection rate was 54.31% (397/731); among infected individuals 77.83% (307/397) were infected with type Ⅰ strain, 22.67% (90/397) were infected by type Ⅱ strain. Annual household income ( χ2=0.419, 0.410, 0.213, all P>0.05), smoking history (χ 2=0.071, P>0.05), drinking history ( χ2=0.071, P>0.05), dining place ( χ2=0.009, P>0.05), gastrointestinal symptoms ( χ2=0.047, P>0.05), family history of gastric disease ( χ2=0.069, P>0.05), and history of gastric cancer ( χ2=0.004, P>0.05) had no significant differences between H. pylori-positive and -negative groups, but the infection rate in individuals with higher education level was lower ( χ2=4.449, P<0.05). The infection rate was significantly higher in≥18 age groups compared with<18 age groups ( χ2=6.531, 23.362, 20.671, 24.244, 37.948, 14.597 and 5.170, all P<0.05). The familial H. pylori infection rate was 87.59% (233/266), and in 61 families all member were infected (26.18%, 61/233). The positive rate was 23.08% (6/26) in 50 families with children under 18 years when both parents were infected. Among 231 coupled families, both couples were infected in 78 families (33.76%), one couple was infected in 113 families (48.92%), and both couples were not infected in 40 (17.32%). With the increase of marriage time, the infection rate of both spouses increased significantly ( χ2=7.775, 12.662, 15.487, all P<0.05). Conclusions:The distribution of H. pylori infection presents a family cluster pattern, and intrafamilial infection is an important transmission rout of H. pylori. The type I strain of H. pylori is the dominate strain in this area.

Objective:To investigate the effect of sarcopenia on the perioperative clinical outcomes of esophageal squamous cell carcinoma (ESCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 1 148 ESCC patients who were admitted to the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University from January 2020 to December 2021 were collected. There were 789 males and 359 females, aged (67±7)years. All patients under-went thoracoscopic and laparoscopic radical esophagectomy for esophageal cancer. Observation indicators: (1) incidence of sarcopenia in patients with ESCC; (2) comparison of general data between ESCC patients complicated with sarcopenia and those without sarcopenia; (3) comparison of clinical outcomes between ESCC patients complicated with sarcopenia and those without sarcopenia; (4) analysis of influencing factors for sarcopenia in ESCC patients. Measurement data of normal distri-bution were represented by Mean± SD, and comparison between groups was conducted using the t test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test. Ordinal data was analyzed using the Mann-Whitney U test. Logistic regression analysis was used to conduct univariate analysis. Logistic backward stepwise regression model was used to conduct multivariate analysis. Results:(1) Incidence of sarcopenia in patients with ESCC. Among 1 148 ESCC patients, 469 cases were complicated with sarcopenia, 679 were without sarcopenia. The incidence of sarcopenia was 40.854%(469/1 148). Among the 469 patients with sarcopenia, there were 313 males and 156 females. There were 125 cases <65 years old, 145 cases ≥65 years old but <70 years old, 106 cases ≥70 years old but<75 years old, 93 cases ≥75 years old, respectively. (2) Comparison of general data between patients with ESCC complicated with sarco-penia and those without sarcopenia. The age, tumor diameter, body mass index, cases in stage T1, T2, T3, preoperative albumin, preoperative serum prealbumin, psoas muscle index, psoas muscle density were (68±7)years, (3.3±1.5)cm, (22.4±2.9)kg/m 2, 100, 105, 264, (43±4)g/L, (193±38)mg/dL, (3.9±0.8)cm 2/m 2, (48±8)HU of 469 ESCC patients complicated with sarcopenia, versus (66±7)years, (3.2±1.4)cm, (23.8±3.0)kg/m 2, 173, 170, 336, (44±4)g/L, (206±37)mg/dL, (6.0±2.2)cm 2/m 2, (50±7)HU of 679 ESCC patients without sarcopenia, showing significant differences between the two groups ( t=5.74, 2.11, 7.57, Z=-2.93, t=2.25, 5.52,20.36, 4.18, P<0.05). (3) Comparison of clinical outcomes between patients with ESCC complicated with sarcopenia and those without sarcopenia. The duration of postoperative hospital stay, cases with postoperative hospital stay>30 days, pneumonia, acute respiratory failure, anastomotic fistula, and abnormal heart rhythm were (17±9)days, 32, 158, 39, 33, and 103 of 469 ESCC patients complicated with sarcopenia, respectively, versus (15±6)days, 15, 102, 18, 19, and 85 of 679 ESCC patients without sarcopenia, showing significant differences between the two groups ( t=4.89, χ2=15.04, 55.17, 18.86, 11.52, 18.06, P<0.05). (4) Analysis of influencing factors for sarcopenia in ESCC patients. Results of multivariate analysis showed that age ≥65 years was an independent risk factor for sarcopenia in ESCC patients ( odds ratio=1.64, 95% confidence interval as 1.26-2.14, P<0.05). Preoperative serum prealbumin ≥200 mg/dL, psoas muscle density ≥48 HU and body mass index >24 kg/m 2 were independent protective factors for sarcopenia in ESCC patients ( odds ratio=0.64, 0.72, 0.53, 95% confidence interval as 0.50-0.82, 0.56-0.92, 0.41-0.69, P<0.05). Conclusions:Age ≥65 years is an independent risk factor for sarcopenia in ESCC patients. Preoperative serum prealbumin ≥200 mg/dL, psoas muscle density ≥48 HU and body mass index >24 kg/m 2 are independent protective factors for sarcopenia in ESCC patients. Compared with patients without sarcopenia, ESCC patients with sarcopenia are more prone to postoperative compli-cations such as pneumonia, acute respiratory failure, anastomotic fistula, and arrhythmia, and have a longer postoperative hospital stay.

Examining the clinical data of 4 recipients with early duodenal fistula after liver transplantation, this review summarizes proper managements and provided references for the clinical prevention and treatment of this complication.

Objective:To investigate the transcriptomic mechanisms and clinical efficacy of D-CAG regimen for the treatment of acute myeloid leukemia (AML) after failure to initial induction of remission.Methods:The transcriptome data of AML cells before and after the use of dexitabine before August 28, 2021 was searched in Gene Expression Omnibus (GEO) database with "decitabine" as the search term. The R language package was used for differential expression analysis and Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis of the data. Protein-protein interaction network (PPI) analysis was conducted on the STRING online analysis website. The accurate treatment prediction platform designed based on logistic omics theory (EpiMed) was used to make drug-disease-target correlation analysis. The clinical data of 18 AML patients treated with D-CAG regimen after failure to induction of remission with standard anthracycline and cytarabine regimen ("3+7" regimen) in the 305th Hospital of Chinese PLA from October 8, 2015 to July 9, 2018 were searched and analyzed, and the curative effect was evaluated. The effects of the dose and duration of each drug on the efficacy were analyzed.Results:The transcriptome data of AML cells before and after the use of decitabine in GSE40442 dataset of the GPL5188 platform were finally selected, updated on July 10, 2014. A total of 366 differentially expressed genes were screened, including 201 up-regulated genes and 165 down-regulated genes. The differential genes were mainly related to cell cycle regulation, bone marrow leukocyte migration and differentiation, transcriptional regulation, bone marrow hematopoiesis and other signaling pathways. Ten core genes such as ANXA5, IL-10, THBS1, TLR4, JUN and CXCL12 were screened by PPI analysis. Drug-disease-target analysis showed that dexitabine had a potential therapeutic effect on various blood diseases such as diffuse large B-cell lymphoma, thrombocytopenia, T-cell acute lymphocytic leukemia, aplastic anemia, and AML. Of the 18 patients, after initial induction of remission, 7 (38.8%) patients achieved partial remission (PR), and 11 (61.2%) patients had no response (NR); after one cycle of re-induction remission therapy, 9 patients had complete remission (CR), 5 patients had PR, 4 patients had NR, and the overall response rate (ORR) was 77.8% (14/18). Compared with patients with NR, the CR rate was higher in patients with PR after initial induction therapy, which were 85.7% (6/7) and 27.3% (3/11), and the difference was statistically significant ( χ2=5.84, P = 0.025). The median duration of cytarabine in CR patients was longer than that in NR patients [10 d (7-14 d) vs. 5 d (2-8 d), Z = 3.89, P = 0.002] and the median ratio of the number of bone marrow blast cells to the duration cytarabine was lower in CR patients than that in NR patients [2.29 (0.89-9.10) vs. 8.10 (3.00-38.50), Z = -2.19, P = 0.006]; the median dose of cytarabine in CR patients was lower than NR patients, which were 50 mg·m -2·d -1 (30-150 mg·m -2·d -1) and 100 mg·m -2·d -1 (50-500 mg·m -2·d -1), and the difference was not statistically significant ( Z = -1.80, P = 0.074). Conclusions:AML patients with PR after initial induction and failure to initial induction of remission may be more likely to achieve CR after the treatment of D-CAG regimen, and this change may be related to the epigenetic regulation of decitabine.

The new external preparations of tr aditional Chinese medicine （TCM）mainly include transdermal drug delivery preparation and transmucosal drug delivery system. With the development of modern science and technology ，new external preparations of TCM are widely used in internal medicine ，gynecology，pediatrics and other diseases. In order to provide reference for dosage form development of TCM and safe use of drug in clinic ，this paper reviews the research progress of new external preparation technology for TCM （skin penetration method ，carrier encapsulation technology ，etc.），new external dosage forms of TCM（microneedles，gels，patches，film sprays ，suppositories，film agents ，in situ gels ，etc.）. In the future ，the research of new external preparations of TCM should conduct under the guidance of TCM theory ，and pay attention to the new drug delivery system of previous drugs and the development of TCM components of “drug-adjuvant integration ”，strengthen the research on new external preparations of TCM compounds ，and establish an evaluation system in line with the overall characteristics of TCM so as to promote the sustainable development of new external preparations of TCM.

Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD's ACE inhibitory ac-tivities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to un-cover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.