With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.

The gene GeDRP1E encoding dynamin-related protein 1E in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDRP1E gene was carried out by using ExPASy, ClustalW, MEGA, etc. Positive transgenic Arabidopsis plant and potato minituber were obtained with the genetic transformation system of Arabidopsis and potato. The plant height and seed setting rate of transgenic Arabidopsis, and agronomic characters, such as size, weight and starch content of potato minituber of transgenic potato were tested and analyzed. And GeDRP1E gene function was preliminarily investigated. The results showed that the open reading frame of GeDRP1E gene was 1 899 bp in length and 632 amino acids residues were encoded, with a relative molecular weight of 69.90 kDa and a molecular formula of C₃₀₇₉H₄₉₇₃N₈₈₃O₉₃₃S₁₉. It was predicted that the theoretical isoelectric point was 7.27, the instability coefficient was 43.34, and the average hydrophilicity index was -0.259, which was indicative of an unstable hydrophilic protein. GeDRP1E has no transmembrane structure and signal peptide, and was localized in the cytoplasm. The phylogenetic tree showed that GeDRP1E was highly homologous with DRP1E proteins of other plant species, among which GeDRP1E had the highest homology with DcDRP1E (XP_020689662.1) in Dendrobium candidum, reaching 90.05%. GeDRP1E plant expression vector pCambia1300-35Spro-GeDRP1E was constructed by double digests, and Arabidopsis complementary mutant and potato overexpression strain of GeDRP1E gene were obtained by Agrobacterium-mediated gene transformation. Compared with the Arabidopsis AtDRP1E mutant, the height and seed setting rate of the GeDRP1E complementation mutant were rescued. The minituber of GeDRP1E overexpression potato had larger size, heavier weight and higher starch content, comparing to wild-type potato. It was preliminarily induced that GeDRP1E was involved in mitochondrial morphology regulation, which related to the growth and development of Arabidopsis plants and potato miniature. The research results laid a foundation for further elucidating the molecular mechanisms underlying the growth and development of G. elata tuber development.

Objective:To explore the application process, efficacy and safety of MR-guided radiotherapy based on MR-linac in esophageal cancer.Methods:The clinical data of patients with esophageal cancer treated with MR-linac at Shandong Cancer Hospital and Institute from September 2021 to July 2022 were retrospectively analyzed, to investigate the treatment process of esophageal cancer with MR-linac, and to analyze the efficacy and safety of patients. All patients received MR-guided radiotherapy, underwent CT and MR localization, target area delineation, and design of the Monaco treatment planning system plan. Adaptation-to-position adjustment was conducted during the pre-treatment evaluation. The median number of fractions was 25, the median single dose of planning target volume was 1.8 Gy, and the median total dose was 50.2 Gy. Median follow-up was 16 months.Results:Among the 12 patients in the whole group, there were 1 case of cervical esophageal cancer, 3 cases of upper thoracic esophageal cancer, 4 cases of middle thoracic esophageal cancer and 4 cases of lower thoracic esophageal cancer, including 3 cases of neoadjuvant radiotherapy and 9 cases of radical radiotherapy. All patients had a smooth treatment process. The median treatment time was 33 min, and the patients had good compliance. For patients with radical radiotherapy, one month after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 9; six months after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 6. All patients treated with neoadjuvant radiotherapy underwent surgery within 2 months, and one patient achieved pathological complete remission. The most common acute adverse reactions were radiation esophagitis (7 cases) and leukopenia in bone marrow suppression (8 cases), with late-stage adverse reactions being radiation pneumonia (1 case). The adverse reactions to radiotherapy were slight, and no grade 4 or above adverse reactions were observed.Conclusion:The clinical treatment process for esophageal cancer under MR-guided radiotherapy based on MR-linac is feasible, with good curative effects and mild adverse reactions.

Objective To evaluate the maturity and metabolic status of heterotopic ossification(HO)by single-photon emission computed tomography(SPECT)/CT fusion bone imaging.Methods The clinical and SPECT/CT fusion bone imaging data of 57 patients with HO confirmed by pathology or follow-up were analyzed retrospectively.HO was graded by CT,and the characteristics of radioactive concentration of HO were analyzed.Results Of 57 cases,single lesion in 52 cases,and multiple lesions in 5 cases,with a total of 63 lesions,mostly located in the hip joint(55.6%,35/63)and thigh(19.0%,12/63).There were 41 lesions in the middle stage and 22 lesions in the late stage.In the visual evaluation of SPECT/CT fusion bone imaging,the middle stage lesions were mostly clumps or flakes,with moderate or high radioactive concentration(75.6%,31/41),furthermore,the concentration range was larger than or equal to the total or limited range of CT ossification(21/41,50.1%),with high concentration mainly located in the mixed areas of ossification density.The concentration of the late stage lesions was mostly non-radioactive(72.7%,16/22).Conclusion SPECT/CT fusion bone imaging can show the range,degree and maturity of HO radioactive concentration,and can accurately locate the area with osteoblastic activity,which provides scientific basis for the selection of surgical timing.

BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.

Objective To explore the preoperative predictive factors influencing microscopic positive proximal margin in upper gastric cancer,and to establish a nomogram prediction model and to validate it internally.Methods Retrospective analysis of 187 patients with upper gastric cancer operated in the Department of Gastrointestinal Surgery of Hengshui People's Hospital from January 2018 to October 2022 were included in this study.Patients were divided into the microscopic positive proximal margin(the R0 group,n=15)and the negative microscopic proximal margin group(the R1 group,n=172)according to histopathological diagnosis.Preoperative factors that may influence positive upper margin of proximal gastric cancer were collected,including patient age,gender,tumor size,tumor location,Borrmann staging,tumor differentiation,Lauren staging,cT stage and cN stage.Receiver operating characteristic(ROC)curve was used to figure out the optimal cut-off value for predicting positive margin of proximal gastric cancer by tumor length.Multivariate Logistic regression was used to analyze the variables with statistical difference between the two groups,and independent risk factors were screened out,and prediction mode was constructed.The prediction accuracy of the model was verified internally using Bootstrap method.Results The best threshold for predicting positive margin of proximal gastric cancer by tumor length was 4.85 cm.Univariate analysis showed that there were significant differences in tumor length,tumor location,Borrmann staging,Lauren staging,cT staging and cN staging between the two groups(all P＜0.05).Multivariate Logistic regression analysis showed that tumor length>4.85 cm(OR=4.000,95%CI:1.039-15.399),tumor located in esophagogastric junction(OR=7.108,95%CI:1.604-31.494),Borrmann staging Ⅲ—Ⅳ(OR=6.991,95%CI:1.538-31.782),Lauren staging as diffuse or mixed(OR=7.583,95%CI:1.814-31.701)and cT staging as cT4(OR=8.249,95%CI:1.890-36.007)were independent predictors of microscopic positive proximal margin of advanced upper gastric cancer before surgery,and a prediction model was established based on results of multivariate analysis.The area under ROC curve(AUC)value for subjects with the model was 0.862 after internal validation.The calibration curve showed that the model predicted the probability of microscopic positive proximal margin occurrence in good agreement with the probability of actual microscopic positive proximal margin occurrence(Hosmer-Lemeshow χ2=6.145,P=0.523).Conclusion The established nomogram prediction model can predict the probability of positive upper incisal margin of proximal gastric cancer before operation,and provide clinical guidance for formulating surgical strategy.

The gene GeDTC encoding the dicarboxylate-tricarboxylate carrier protein in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDTC gene was carried out by using ExPASY, ClustalW, MEGA, etc. Positive transgenic plants and potato minituber were obtained by virtue of the potato genetic transformation system. Agronomic characters, such as size, weight, organic acid content, and starch content, of potato minituber were tested and analyzed and GeDTC gene function was preliminarily investigated. The results showed that the open reading frame of GeDTC gene was 981 bp in length and 326 amino acid residues were encoded, with a relative molecular weight of 35.01 kDa. It was predicted that the theoretical isoelectric point of GeDTC protein was 9.83, the instability coefficient was 27.88, and the average index of hydrophilicity was 0.104, which was indicative of a stable hydrophilic protein. GeDTC protein had a transmembrane structure and no signal peptide and was located in the inner membrane of mitochondria. The phylogenetic tree showed that GeDTC was highly homologous with DTC proteins of other plant species, among which GeDTC had the highest homology with DcDTC(XP＿020675804.1) in Dendrobium candidum, reaching 85.89%. GeDTC overexpression vector pCambia1300-35Spro-GeDTC was constructed by double digests, and transgenic potato plants were obtained by Agrobacterium-mediated gene transformation. Compared with the wild-type plants, transgenic potato minituber harvested by transplanting had smaller size, lighter weight, lower organic acid content, and no significant difference in starch content. It is preliminarily induced that GeDTC is the efflux channel of tricarboxylate and related to the tuber development, which lays a foundation for further elucidating the molecular mechanism of G. elata tuber development.
Gastrodia/genetics* ; Phylogeny ; Amino Acids ; Cloning, Molecular

ObjectiveTo analyze the community structure of endophytes in Panax quinquefolium root and explore the dominant endophytic bacteria and fungi， to provide scientific basis for the establishment of endophytic microbial bank in P. quinquefolium root. MethodInternal Transcribed Spacer （ITS） sequencing and 16S sequencing were performed on six P. quinquefolium root samples collected from Wendeng， Shandong province on PacBio Sequel Ⅱ. ResultA total of 8 phyla， 11 classes， 23 orders， 27 families and 53 genera of endophytic bacteria were identified in P. quinquefolium root， among which an unidentified Burkholderiaceae and an unidentified Rhizobiaceae were dominant. A total of 9 phyla， 23 classes， 35 orders， 43 families and 48 genera of endophytic fungi were identified in P. quinquefolium root， among which an unclassified Helotiales and Pseudogymnoascus were dominant. The community structure of endophytic bacteria revealed that the roots were selectively enriched with nitrogen-fixing bacteria such as unidentified Rhizobiaceae， Bradyrhizobium and Herbaspirillum， which suggested that nitrogen is important for the growth of P. quinquefolium root. The community structure of endophytic fungi indicated that P. quinquefolium in Shandong province might be infected by unclassified Helotiales. ConclusionThere is a rich diversity of endophytic bacteria and fungi in P. quinquefolium root， which provides scientific basis for studying the interaction of the plant with endophytic microorganisms and screening the endophytes to promote the growth of P. quinquefolium root.

Objective To investigate the association between serum alkaline phosphatase (ALP) and type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Methods A total of 599 patients with T2DM who were hospitalized in Department of Endocrinology, Affiliated Hospital of Jiangsu University, from July 2016 to December 2018 were enrolled as subjects. According to the presence or absence of NAFLD, the patients were divided into NAFLD group with 286 patients and non-NAFLD group with 313 patients, and according to the results of abdominal ultrasound, the patients with NAFLD were divided into mild group with 111 patients, moderate group with 105 patients, and severe group with 70 patients. General clinical data were compared between groups. The independent samples t - test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between three groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. Pearson correlation analysis and Spearman correlation analysis were used to investigate the correlation between ALP and clinical indices, and a logistic regression analysis was used to investigate the influencing factors for NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with history of hypertension ( χ 2 =7.864, P < 0.05), systolic blood pressure ( t =-2.226, P < 0.05), diastolic blood pressure ( t =-3.800, P < 0.05), body mass index (BMI) ( t =-11.842, P < 0.05), waist circumference (WC) ( t =-9.150, P < 0.05), fasting insulin (FINS) ( Z =-6.173, P < 0.05), fasting C-peptide ( t =-5.419, P < 0.05), serum uric acid ( t =-4.957, P < 0.05), low-density lipoprotein cholesterol ( t =-2.702, P < 0.05), triglyceride ( Z =-9.376, P < 0.05), total cholesterol (TC) ( t =-3.016, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( Z =-5.794, P < 0.05), alanine aminotransferase (ALT) ( Z =-6.737, P < 0.05), aspartate aminotransferase (AST) ( Z =-4.389, P < 0.05), gamma-glutamyl transpeptidase (GGT) ( Z =-7.764, P < 0.05), and ALP ( t =-2.833, P < 0.05), as well as significantly lower age ( t =2.184, P < 0.05) and high-density lipoprotein cholesterol ( Z =-5.273, P < 0.05). The severity of NAFLD (mild, moderate or severe) was positively correlated with age ( r s =0.140, P < 0.05), BMI ( r s =0.239, P < 0.05), WC ( r s =0.222, P < 0.05), FINS ( r s =0.191, P < 0.05), HOMA-IR ( r s =0.218, P < 0.05), ALT ( r s =0.188, P < 0.05), AST ( r s =0.279, P < 0.05), GGT ( r s =0.202, P < 0.05), and ALP ( r s =0.361, P < 0.05). In the patients with T2DM and NAFLD, ALP was positively correlated with HbAlc ( r =0.149, P < 0.05), fasting plasma glucose ( r =0.146, P < 0.05), HOMA-IR ( r s =0.132, P < 0.05), TC ( r =0.151, P < 0.05), ALT ( r s =0.210, P < 0.05), AST ( r s =0.192, P < 0.05), and GGT ( r s =0.297, P < 0.05). The logistic regression analysis showed that ALP was an influencing factor for NAFLD in patients with T2DM (odds ratio=1.013, 95% confidence interval: 1.004-1.023, P < 0.05). Conclusion Elevated serum ALP is a risk factor for T2DM with NAFLD and is closely associated with hyperglycemia, insulin resistance, and hyperlipemia, and ALP may play a role in the development and progression of T2DM and NAFLD.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*