Objective To explore the clinical value of artificial intelligence (AI) quantitative parameters in distinguishing pathological grades of stageⅠ invasive adenocarcinoma (IAC). Methods Clinical data of patients with clinical stageⅠ IAC admitted to Yantaishan Hospital Affiliated to Binzhou Medical University from October 2018 to May 2023 were retrospectively analyzed. Based on the 2021 WHO pathological grading criteria for lung adenocarcinoma, IAC was divided into gradeⅠ, grade Ⅱ, and grade Ⅲ. The differences in parameters among the groups were compared, and logistic regression analysis was used to evaluate the predictive efficacy of AI quantitative parameters for grade Ⅲ IAC patients. Parameters were screened using least absolute shrinkage and selection operator (LASSO) regression analysis. Three machine learning models were constructed based on these parameters to predict grade Ⅲ IAC and were internally validated to assess their efficacy. Nomograms were used for visualization. Results A total of 261 IAC patients were included, including 101 males and 160 females, with an average age of 27-88 (61.96±9.17) years. Six patients had dual primary lesions, and different lesions from the same patient were analyzed as independent samples. There were 48 patients of gradeⅠ IAC, 89 patients of grade Ⅱ IAC, and 130 patients of grade Ⅲ IAC. There were statitical differences in the AI quantitive parameters such as consolidation/tumor ratio (CTR), ect among the three goups. (P<0.05). Univariate analysis showed that the differences in all variables except age were statistically significant (P<0.05) between the group gradeⅠ+grade Ⅱand the group grade Ⅲ . Multivariate analysis suggested that CTR and CT standard deviation were independent risk factors for identifying grade Ⅲ IAC, and the two were negatively correlated. Grade Ⅲ IAC exhibited advanced TNM staging, more pathological high-risk factors, higher lymph node metastasis rate, and higher proportion of advanced structure. CTR was positively correlated with the proportion of advanced structures in all patients. This correlation was also observed in grade Ⅲ but not in gradeⅠand grade ⅡIAC. CTR and CT median value were selected by using LASSO regression. Logistic regression, random forest, and XGBoost models were constructed and validated, among which, the XGBoost model demonstrated the best predictive performance. Conclusion Cautious consideration should be given to grade Ⅲ IAC when CTR is higher than 39.48% and CT standard deviation is less than 122.75 HU. The XGBoost model based on combined CTR and CT median value has good predictive efficacy for grade Ⅲ IAC, aiding clinicians in making personalized clinical decisions.

Objective     To explore the clinical value of artificial intelligence (AI) quantitative parameters of pulmonary ground-glass nodules (GGN) in predicting the degree of infiltration. Methods     A retrospective analysis of 168 consecutive patients with 178 GGNs in our hospital from October 2019 to May 2021 was performed, including 43 males and 125 females, aged 21-78 (55.76±10.88) years. Different lesions of the same patient were analyzed as independent samples. Totally, 178 GGNs were divided into two groups, a non-invasive group (24 adenocarcinoma in situ and 77 minimally invasive adenocarcinoma), and an invasive group (77 invasive adenocarcinoma). We compared the difference of AI quantitative parameters between the two groups, and evaluated predictive valve by receiver operating characteristic curve and binary logistic regression model. Results     (1) Except for the gender (P=0.115), the other parameters, such as maximal diameter [15.10 (11.50, 21.60) mm vs. 8.90 (7.65, 11.15) mm], minimum diameter [10.80 (8.85, 15.20) mm vs. 7.40 (6.10, 8.95) mm], proportion of consolidation/tumor ratio [13.58% (1.61%, 63.76%) vs. 0.00% (0.00%, 0.67%)], mean CT value [–347.00 (–492.00, –101.50) Hu vs. –598.00 (–657.50, –510.00) Hu], CT maximum value [40.00 (–40.00, 94.50) Hu vs. –218.00 (–347.00, –66.50) Hu], CT minimum value [–584.00 (–690.50, –350.00) Hu vs. –753.00 (–786.00, –700.00) Hu], danger rating (proportion of high-risk nodules, 92.2% vs. 66.3%), malignant probability [91.66% (85.62%, 94.92%) vs. 81.81% (59.98%, 90.29%)] and age (59.93±8.53 years vs. 52.04±12.10 years) were statistically significant between the invasive group and the non-invasive group (all P<0.001). (2) The highest predictive value of a single quantitative parameter was the maximal diameter (area under the curve=0.843), the lowest one was the risk classification (area under the curve=0.627), the combination of two among the three parameters (maximal diameter, mean CT value, and consolidation/tumor ratio) improved the predictive value entirely. (3) Logistic regression analysis showed that maximal diameter and mean CT value both were the independent risk factor for predicting invasive adenocarcinoma. (4) When the threshold of v was 1.775%, the diagnostic sensitivity of invasive adenocarcinoma was 0.753 and the specificity was 0.851. Conclusion     AI quantitative parameters can effectively predict the degree of infiltration of GGNs and provide a reliable reference basis for clinicians.

Objective:To investigate the receptor pathways of glycated basic fibroblast growth factor (bFGF) on proliferation and vascularization of human dermal microvascular endothelial cells (HDMECs).Methods:The experimental research method was used. Glycated bFGF stimulating solution was prepared with glucose and bFGF. HDMECs of the third to sixth passages were used in the experiment. Cells were divided into small interfering RNA (siRNA)-positive control group, siRNA-negative control group, siRNA-receptor for advanced glycation end product (RAGE) group, and siRNA-receptor for fibroblast growth factor (FGFR) group and transfected with siRNA-positive control glyceraldehyde-3-phosphate dehydrogenase, siRNA-negative control, siRNA-RAGE, and siRNA-FGFR for 4 to 6 hours, and then were added into HDMEC culture medium for routine culture. The transfection effect of siRNA was identified by reverse transcription polymerase chain reaction. The cells were divided into normal control group, glycated bFGF alone group, siRNA-RAGE alone group, and siRNA-RAGE+ glycated bFGF group, and seeded into 96-well plate and 6-well plate. Cells in siRNA-RAGE alone group and siRNA-RAGE+ glycated bFGF group were transfected with siRNA-RAGE and then were added into HDMEC culture medium for routine culture. After two days, the original HDMEC culture medium was discarded, and cells in siRNA-RAGE alone group were routinely cultured in HDMEC culture medium, cells in siRNA-RAGE+ glycated bFGF group were routinely cultured in glycated bFGF stimulating solution. Cells in normal control group were routinely cultured in HDMEC culture medium, and cells in glycated bFGF alone group were routinely cultured in glycated bFGF stimulating solution. After transfection with siRNA-RAGE, cells were seeded into 48-well plate and divided into siRNA-RAGE alone group and siRNA-RAGE+ glycated bFGF group. Another cells were directly seeded into 48-well plate without transfection and divided into normal control group and glycated bFGF alone group. Cells in the 4 groups were conducted with the corresponding treatment as above. Cells were divided into normal control group, glycated bFGF alone group, siRNA-FGFR alone group, and siRNA-FGFR+ glycated bFGF group and seeded into 96-, 6-, and 48-well plates, respectively, with the corresponding treatment the same as above. Only siRNA-RAGE was replaced by siRNA-FGFR. Cell counting kit 8 method was used to determine the proliferation of cells after 2 days of culture (sample number was 6), flow cytometry was used to detect the apoptosis of cells after 2 days of culture (sample number was 3), tube forming test was used to detect the angiogenesis of cells after 6 hours of culture (sample number was 4). Data were statistically analyzed with one-way analysis of variance and least significant difference t test. Results:At the 200 bp band, there were no target genes in siRNA-positive control group, siRNA-RAGE group, or siRNA-FGFR group, but target genes were detected in siRNA-negative control group, indicating the success of siRNA transfection. After 2 days of culture, the absorbance value of cells in glycated bFGF alone group was significantly lower than that of normal control group ( t=2.359, P<0.05); absorbance value of cells in siRNA-RAGE+ glycated bFGF group was significantly higher than that of glycated bFGF alone group ( t=3.858, P<0.01), which was similar to that of siRNA-RAGE alone group ( t=2.148, P>0.05). The absorbance value of cells in siRNA-FGFR+ glycated bFGF group was similar to that of glycated bFGF alone group ( t=0.805, P>0.05), but significantly lower than that of siRNA-FGFR alone group ( t=4.201, P<0.01). After 2 days of culture, the apoptotic rate of cells in glycated bFGF alone group was significantly higher than that of normal control group ( t=2.416, P<0.05). The apoptotic rate of cells in siRNA-RAGE+ glycated bFGF group was significantly lower than the rates in glycated bFGF alone group and siRNA-RAGE alone group ( t=3.861, 2.724, P<0.05 or P<0.01). There were no statistically significant differences in apoptosis rate of cells among normal control group, glycated bFGF alone group, siRNA-FGFR alone group, and siRNA-FGFR+ glycated bFGF group ( F=2.218, P>0.05). After 6 hours of culture, the number of tubules of cells in normal control group (636±5) was significantly more than that of glycated bFGF alone group (580±8, t=10.825, P<0.01), and the number of tubules of cells in siRNA-RAGE+ glycated bFGF group (647±10) was significantly more than those of glycated bFGF alone group and siRNA-RAGE alone group (628±4, t=13.040, 3.641, P<0.01). After 6 hours of culture, the number of tubules of cells in siRNA-FGFR+ glycated bFGF group (619±5) was more than that of glycated bFGF alone group ( t=9.000, P<0.01), but less than that of siRNA-FGFR alone group (632±3, t=2.814, P<0.05). Conclusions:Glycated bFGF affects the proliferation and angiogenesis of HDMEC through RAGE pathway, which may be one of the reasons for impaired wound healing of diabetic skin.

Objective:To investigate the receptor pathways of glycated basic fibroblast growth factor (bFGF) on proliferation and vascularization of human dermal microvascular endothelial cells (HDMECs).Methods:The experimental research method was used. Glycated bFGF stimulating solution was prepared with glucose and bFGF. Cells of the third to sixth passages were subcultured from the HDMEC primary cell line. The cells were divided into normal control group, glycated bFGF alone group, small interfering RNAs (siRNA)-advanced glycation end product receptor (RAGE) alone group, and siRNA-RAGE+glycated bFGF group, and seeded into 96-well plate with 6 wells in each group, and seeded into 6-well plate with 3 wells in each group. Cells in siRNA-RAGE alone group and siRNA-RAGE+glycated bFGF group were transfected with siRNA-RAGE and then were added into HDMEC culture medium for routine culture. After two days, the original HDMEC culture medium was discarded, and cells in siRNA-RAGE alone group were routinely cultured in HDMEC culture medium, cells in siRNA-RAGE+glycated bFGF group were routinely cultured in glycated bFGF stimulating solution. Cells in normal control group were routinely cultured in HDMEC culture medium, and cells in glycated bFGF alone group were routinely cultured in glycated bFGF stimulating solution. After transfection with siRNA-RAGE, cells were seeded into 48-well plate and divided into siRNA-RAGE alone group and siRNA-RAGE+glycated bFGF group, with 4 wells in each group. Another cells were directly seeded into 48-well plate without transfection and divided into normal control group and glycated bFGF alone group, with 4 wells in each group. Cells in normal control group and siRNA-RAGE group were routinely cultured in HDMEC culture medium. Cells in siRNA-RAGE alone group and siRNA-RAGE+glycated bFGF group were routinely cultured in glycated bFGF stimulating solution. Cells were divided into normal control group, glycated bFGF alone group, siRNA-fibroblast growth factor receptor (FGFR) alone group, and siRNA-FGFR+glycated bFGF group and seeded into 96-, 6- and 48-well plates. respectively. Cell density, sample number, and corresponding treatment were the same as before. Only siRNA-RAGE was replaced by siRNA-FGFR. Cells were divided into siRNA-positive control group, siRNA-negative control group, siRNA-RAGE group, and siRNA-FGFR group and transfected with siRNA-glyceraldehyde-3-phosphate dehydrogenase positive control, siRNA-negative control, siRNA-RAGE, and siRNA-FGFR for 4 to 6 hours, and then were added into HDMEC culture medium for routine culture. The transfection effect of siRNA was identified by reverse transcription PCR. Cell counting kit 8 method was used to determine the proliferation of cells after 2 days of culture (sample number was 6), flow cytometry was used to detect the apoptosis of cells after 2 days of culture (sample number was 3), tube forming test was used to detect the angiogenesis of cells cultured after 6 hours of culture (sample number was 4). Data were statistically analyzed with one-way analysis of variance and least significant difference t test. Results:At the 200 bp band, there were no complementary DNA (cDNA) bands in siRNA-positive control group, siRNA-RAGE group, and siRNA-FGFR group, but cDNA bands were detected in siRNA-negative control group, indicating the success of siRNA transfection. After 2 days of culture, the absorbance value of cells in glycated bFGF alone group was significantly lower than that of normal control group ( t=2.359, P<0.05); absorbance value of cells in siRNA-RAGE+glycated bFGF group was significantly higher than that of glycated bFGF alone group ( t=3.858, P<0.01), which was similar to that of siRNA-RAGE alone group ( t=2.148, P>0.05). The absorbance value of cells in siRNA-FGFR+glycated bFGF group was similar to that of glycated bFGF alone group ( t=0.805, P>0.05), but significantly lower than that of siRNA-FGFR alone group ( t=4.201, P<0.01). After 2 days of culture, the apoptotic rate of cells in glycated bFGF alone group was significantly higher than that of normal control group ( t=2.416, P<0.05). The apoptotic rate of cells in siRNA-RAGE+glycated bFGF group was significantly lower than the rates in glycated bFGF alone group and siRNA-RAGE alone group ( t=3.861, 2.724, P<0.05 or P<0.01). There were no significant differences in apoptosis rate of cells among normal control group, glycated bFGF alone group, siRNA-FGFR alone group, and siRNA-FGFR+glycated bFGF group ( F=2.218, P>0.05). After 6 hours of culture, the number of tubules of cells in normal control group (636±5) was significantly more than that of glycated bFGF alone group [580±8, t=10.825, P<0.01], and the number of tubules of cells in siRNA-RAGE+glycated bFGF group (647±10) was significantly more than those of glycated bFGF alone group and siRNA-RAGE alone group (628±4, t=13.040, 3.641, P<0.01). After 6 hours of culture, the number of tubules of cells in siRNA-FGFR+glycated bFGF group (619±5) was significantly more than that of glycated bFGF alone group ( t=9.000, P<0.01), but less than that of siRNA-FGFR alone group (632±3, t=2.814, P<0.05). Conclusions:Glycated bFGF affects the angiogenesis of HDMEC through RAGE pathway, which may be one of the reasons for the impaired wound healing of diabetic skin.

OBJECTIVE： To explore potential mechanism of “Astragalus membranaceus-Draba nemorosa” couplet medicine for heart failure. METHODS： By network pharmacology， based on drug-like and oral bioavailability， the active components of “A. membranaceus-D. nemorosa” for chronic heart failure were screened and the targets of treating chronic heart failure were predicted by using TCMSP，GeneCards database， OMIM database and DRAR-CPI. The active component-chronic heart failure target network was established by Cytoscape 3.6.0 software. The protein-protein interaction network was constructed by utilizing STRING database. Then top 5 targets in the list of connectivity were screened and performed a molecular docking in molecular docking server. Finally， GO bioprocess analysis and KEGG pathway enrichment analysis were performed in DAVID database. RESULTS： The study predicted 28 active components in total， including 20 A. membranaceus and 12 D. nemorosa， such as kaempferol and quercetin， there were four components in common. Totally 92 target gene of active components were obtained， including heat shock protein 90α （HSP90AA1）， tyrosine protein kinase SRC gene， etc. Results of GO bioprocess analysis showed an association with mitochondrial electron transport， mitochondrial intima， cytoplasmic sol， extracellular body， mitochondrial matrix and drug response. KEGG pathway enrichment analysis showed a link with MAPK signal pathway， TGF signal pathway， PI3K signal pathway， cAMP signal pathway， protein kinase B signal pathway， EPK1 signal pathway and NF-κB signal pathway. CONCLUSIONS： “A. membranaceus-D. nemorosa” couplet medicine exerts therapeutic effects on heart failure from multiple targets as HSP90AA1， SRC and mitochondrial electron transport and MAPK signaling pathway. The study can provide reference for further researches on its material basis and mechanism.

OBJECTIVE： To study the mechanism of Prunus persica-Carthamus tinctorius couplet medicine in the treatment of osteonecrosis of the femoral head （ONFH）. METHODS： The network pharmacology was adopted. The active components of P. persica -C. tinctorius couplet medicine and ONFH target were screened through TCM systematic pharmacological analysis platform target （TCMSP）， DRAR-CPI， hnuman gene database （GeneCards） and online medelian inheritance in man （OMIM） using oral availability of compounds （OB）＞30％ and drug like （DL）＞0.18 as standard. Network topology attribute analysis software Cytoscape 3.6.0 was utilized to construct the active components-ONFH targets network. Target protein interaction network was established on the basis of STRING database， and top 5 target proteins in the list of connectivity were screened， and molecular docking server was used to predict the combination activity of active components from P. persica -C. tinctorius couplet medicine. The biological processes of target gene ontology （GO） and metabolic pathways in Kyoto encyclopedia of genes and genomes （KEGG） were enriched and analyzed by DAVID. RESULTS： A total of 44 active components were screened from P. persica -C. tinctorius couplet medicine， including baicalin， quercetin， etc.， and 78 targets related to ONFH including VEGF， VEGI， CRP， etc. Through analysis of molecular docking server， binding activity of active components of P. persica -C. tinctorius couplet medicine to target protein was strong. GO and KEGG pathway enrichment analysis showed that biological process of P. persica -C. tinctorius couplet medicine for ONFH was related with negative regulation of apoptosis process and positive regulation of nuclear factor-κB transcription factor， mainly through regulating secretory glycoprotein signaling pathway， melanogenesis signaling pathway， VEGF signaling pathway， signaling pathway of basal cell carcinoma， adenosine-activated protein kinase signaling pathway. CONCLUSIONS： This study preliminarily validates the major targets and pathways of P. persica -C. tinctorius couplet medicine for ONFH， which lay a foundation for further study on their pharmacological action.

OBJECTIVE： To systematically evaluate therapeutic efficacy of modified Cangfu daotan decoction （MCDD） combined with chemical medicine versus chemical medicine alone in the treatment of polycystic ovarian syndrome （PCOS）， and to provide evidence-based reference for clinical decision. METHODS： Retrieved from PubMed， Embase， Cochrane Library， CJFD， Wanfang database， VIP and CBM， randomized controlled trials （RCTs） about MCDD combined with chemical medicine [ethynestradiol cycloprogesterone （Diane-35）， clomiphene， metformin] （trial group） versus chemical medicine alone （control group） in the treatment of PCOS were collected. After data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale， Meta-analysis was conducted for total response rate， serum hormone level （FSH， LH， LH/FSH， testosterone）， BMI， ovulation rate and physical signs （hirsutism， acne） by using Stata 14.0 software. Trial sequential analysis（TSA）was conducted by using TSA 0.9 software. RESULTS： A total of 20 RCTs were included， involving 1 484 patients. Results of Meta analysis showed that total response rate [RR＝1.13，95％CI （1.02，1.24），P＜0.05]， serum hormone level {FSH [WMD＝－0.59，95％CI（－0.98，－0.20），P＜0.05]，LH [WMD＝－0.95，95％CI（－1.41， －0.52），P＜0.05]，LH/FSH [WMD＝－1.04，95％CI（－1.78，－0.33），P＜0.05]，testosterone [WMD＝－0.93，95％CI（－1.38，－0.28），P＜0.05]}， BMI [SMD＝－1.01，95％CI  （－1.76，－0.27），P＜0.05]， ovulation rate [RR＝1.17，95％CI（1.02，1.34），P＜0.05] and physical signs {hirsutism [WMD＝－0.48，95％CI（－0.86， －0.10），P＜0.05]， acne [WMD＝－1.16，95％CI（－1.56，－0.75），P＜0.05]} of trial group were all better than those of control group， with statistical significance. TSA showed that there are reliable evidences for MCDD combined with chemical medicine in the treatment of PCOS. CONCLUSIONS： Versus chemical medicine alone in the treatment of PCOS， MCDD combined with chemical medicine can improve total response rate and ovulation rate， reduce serum hormone levels， BMI and physical signs.

Objective To identify the cross-reactive antigens shared by Mycobacteria smegmatis(MS) and Mycobacteria tuberculosis(MTB) and to analyze their antigenicity.Methods Bacterial antigens were extracted from strains of MS and MTB by ultrasonication.Western blot assay was performed to analyze common antigens that reacted with both of the antiserum samples against MS and MTB.The extracted bacterial antigens were mixed with incomplete Freund′s adjuvant and then were injected into muscles of mice.Cytokines secreted by murine spleen lymphocytes following stimulation with various antigens of MS and MTB were determined by ELISPOT and flow cytometry on the 7th day.IgG levels in serum samples were detected by ELISA 7 days after injection.Results There were cross-reactive antigens shared by MS and MTB.Potent humoral immune responses and cellular immunity against both MS and MTB could be induced by those cross-reactive antigens after sensitization the mice by either MS or MTB antigens.Cytokines of IL-2 and IFN-γ in CD4+ and CD8+T cells of mice stimulated with MS or MTB antigens were significantly increased as compared with those of non-sensitization group and those of Brucella antigens stimulation group.ConclusionCross-reactive antigens shared by MS and MTS can effectively promote specific immune reactions to the infection of MTB, which provides a scientific basis for the development of tuberculosis vaccines.

OBJECTIVETo assess the quality of reporting by randomized controlled trial (RCT) related to dental implants in China during 2000 to 2012 by using the revised Jadad scale and consolidated standards of reporting trials (CONSORT) (2010) statement.

METHODSThe following electronic databases were searched: Chinese Biomedical Literature Database, Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, PubMed, and EMBASE. A total of 19 journals of stomatology in China were also searched manually. The qualities of RCT with dental implant published between 2000 and 2012 were assessed using CONSORT (2010) statement and revised Jadad scale.

RESULTSTwenty-eight RCTs related to dental implants were identified. The quality of reporting in 28 articles was low. The mean revised Jadad score was 1.29 ± 0.71 and the CONSORT (2010) score was 9.75 ± 3.60.

CONCLUSIONThe methodological qualities of the included studies on dental implants are generally low, and reporting quality remain unsatisfactory.

Objective To assess the quality of reporting by randomized controlled trial (RCT) related to dental implants in China during 2000 to 2012 by using the revised Jadad scale and consolidated standards of reporting trials (CONSORT) (2010) statement. Methods The following electronic databases were searched: Chinese Biomedical Literature Database, Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, PubMed, and EMBASE. A total of 19 journals of stomatology in China were also searched manually. The qualities of RCT with dental implant published between 2000 and 2012 were assessed using CONSORT (2010) statement and revised Jadad scale. Results Twenty-eight RCTs related to dental implants were identified. The quality of reporting in 28 articles was low. The mean revised Jadad score was 1.29±0.71 and the CONSORT (2010) score was 9.75±3.60. Conclusion The methodological qualities of the included studies on dental implants are generally low, and reporting quality remain unsatisfactory.