OBJECTIVE: To investigate the diagnostic efficacy of ^99mTc-MDP three-phase bone scintigraphy (TPBS) combined with C-reactive protein (CRP) for periprosthetic joint infection (PJI). METHODS: The clinical data of 198 patients who underwent revision surgery of artificial joint between January 2017 and January 2024 and received TPBS examination before surgery were retrospectively analyzed. There were 77 males and 121 females with an average age of 63.74 years ranging from 24 to 92 years. There were 90 cases of hip arthroplasty and 108 cases of knee arthroplasty. PJI was diagnosed according to the 2013 American Musculoskeletal Infection Society (MSIS) standard diagnostic criteria. The sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predict value (PPV) were calculated. The receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of the three methods, and the area under curve (AUC) was used to evaluate the diagnostic performance. RESULTS: According to the 2013 MSIS criteria, 116 cases were diagnosed as PJI, and the remaining 82 cases were aseptic loosening. The cases of PJI diagnosed by TPBS, CRP, and TPBS-CRP were 125, 109, and 137 respectively, and the cases of aseptic loosening were 73, 89, and 61 respectively. The sensitivity, accuracy, NPV, and PPV of TPBS-CRP combination in the diagnosis of PJI were higher than those of TPBS and CRP, but the specificity was lower than that of TPBS and CRP. ROC curve analysis further showed that the AUC value of TPBS-CRP combination was better than that of TPBS and CRP. The severity of bone defect and the duration of symptoms in patients with false positive TPBS diagnosis were worse than those in patients with true negative TPBS diagnosis (P<0.05), but there was no significant difference in the survival time of prosthesis between the two groups (P>0.05). Among the patients diagnosed with PJI by TPBS, CRP, and TPBS-CRP, 49, 35, and 54 patients had received antibiotic treatment 2 weeks before diagnosis, respectively. There was no significant difference in the diagnostic accuracy of TPBS and TPBS-CRP before diagnosis between patients treated with and without antibiotics and those not treated (P>0.05). The diagnostic accuracy of antibiotic therapy before CRP diagnosis was significantly lower than that of untreated patients (P<0.05). CONCLUSION TPBS and CRP have limited specificity in differentiating PJI from aseptic loosening. The TPBS-CRP combination diagnostic method can synergize the local bone metabolic characteristics and systemic inflammatory response to achieve higher diagnostic accuracy, but caution should be exercised in patients with severe bone defects and longer symptom duration.
Humans ; Prosthesis-Related Infections/blood* ; Middle Aged ; Male ; Female ; Aged ; C-Reactive Protein/metabolism* ; Retrospective Studies ; Adult ; Radionuclide Imaging/methods* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged, 80 and over ; Technetium Tc 99m Medronate ; Arthroplasty, Replacement, Hip/adverse effects* ; Sensitivity and Specificity ; Knee Prosthesis/adverse effects* ; ROC Curve ; Reoperation ; Radiopharmaceuticals ; Young Adult

It is the current confusion encountered by integrated Chinese and Western medicine that how to find the breakthrough direction of integrating Chinese and Western medicine， from crossover to integration to innovation， and open up a new horizon of integrated Chinese and Western medicine. The progress of Chinese medicine lay in expanding the scope of diagnosis and treatment with the help of modern diagnostic and therapeutic equipments and developing “micro” identification， while the progress of Western medicine lay in looking at “macro” and developing systemic medicine and integrated medicine， both of which are in the direction of each other. The “state-target identification and treatment” may become an important way to build a modern diagnosis and treatment system of integrated Chinese and Western medicine， and the thinking mode of “from target to state” is a further refinement and development on the basis of the theoretical system of “state-target identification and treatment”， which provided a clearer solution for the current stage of the integrated Chinese and Western medicine model， and pointed out the important development direction for the future integrated Chinese and Western medicine. From the perspective of strategic level and diagnosis and treatment practice， it integrated the “target-state” thinking mode into the modern diagnosis and treatment model of the integrated Chinese and Western medicine， i.e.， “Western medicine as the basis and treating with Chinese medicine； Chinese medicine as the basis and treating with Western medicine”. On the one hand， Western medicine should strengthen the reference to the traditional theories and holism of Chinese medicine， and advocate a higher level of education on the integrated Chinese and Western medicine under the guidance of the traditional theories of Chinese medicine. On the other hand， the “from target to state” mode of thinking should be applied to guide the establishment of diagnostic and treatment strategies and clinical selection of medicines in clinical practice， so as to locate the target and adjust the body state in a gradual and orderly manner， and to provide practical methods for the modern clinical work of the integrated Chinese and Western medicines. Chinese and Western medicine systems can learn from each other， combine organically， give full play to their respective strengths， and form an internal law， so as to make breakthroughs and innovations in the integrated Chinese and Western medicine model.

This study was performed to investigate the effects of mitogen-activated protein kinase(MAPK)pathway inhibitors on the expression of PD-L1 in dendritic cells and the T lymphocyte immune response in gram negative bacterial sepsis.The immunosuppression model of bacterial sepsis was established by treating the dendritic cells with bacterial endotoxin.The MAPK pathways inhibitors were applied to block pathways of dendritic cells,and then the PD-L1 expression on dendritic cells were detected by flow cytometry and Western blotting.Furthermore,the levels of T lymphocyte proliferation response and cytotoxic T cell response in mixed lymphocyte co-culture experiments were detected by cell proliferation assay kit and enzyme-linked immunospot assay kit,respectively.Data showed that the PD-L1 expression of dendritic cells were significantly up-regulated in the model group compared with the control group,while the levels of T lymphocyte proliferation response and cytotoxic T cell response in the model group were significantly reduced(P<0.05).Then compared with the model group,the PD-L1 expression of dendritic cells were significantly down-regulated in the SB203580/model group(P<0.05),meanwhile the levels of T lymphocyte proliferation response and cytotoxic T cell response were both significantly increased in SB203580/model group and αPD-L1/model group(P<0.05).In conclusion,the p38 signaling pathway could regulate PD-L1 expression of dendritic cells in bacterial sepsis.The application of p38 pathway inhibitors could partially reduce the PD-L1 expression of dendritic cells and reverse T lymphocyte immunosuppression in bacterial sepsis.

Objective To investigate the effect and its molecular mechanism of phosphoglycerate mutase 5 (PGAM5) mediated pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57 mouse models of liver IRI were established and randomly divided into the 6 h reperfusion (6 h group) and 12 h reperfusion (12 h group), and sham operation group (sham group) was established too, 10 rats in each group. The effect of IRI on the parameters in the liver tissues and serum samples was evaluated. The expression levels of PGAM5 and cysteinyl aspartate specific proteinase (Caspase)-1 in the liver tissues during IRI were quantitatively detected. The IRI models of liver cells were established (IRI group). The IRI models of liver cells were established after pretreatment with Caspase-1 inhibitor Z-YVAD-FMK (inhibitor group). The untreated AML12 cells were allocated into the control group. The effect of inhibiting Caspase-1 activity on pyroptosis was analyzed. AML12 cells were transfected with PGAM5 small interfering ribonucleic acid (siRNA) (siRNA group) and siRNA-negative control (siRNA-NC) (siRNA-NC group) by liposome 3000, and then IRI models of liver cells were established. The untreated AML12 cells were assigned into the control group. The effect of PGAM5 mediated pyroptosis on IRI of liver cells was assessed. Results In the 6 h and 12 h groups, partial liver cell edema, hepatic sinusoid narrowing, central vein congestion and occasional spot necrosis were observed in the mouse liver tissues, and these changes in the 12 h group were more aggravated than those in the 6 h group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 h and 12 h groups were higher than those in the sham group, and the values in the 12 h group were higher than those in the 6 h group. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased in the 6 h and 12 h groups, and the values in the 12 h group were lower than those in the 6 h group. The relative expression levels of IL-1β messenger ribonucleic acid (mRNA) in the mouse liver tissues in the 6 h and 12 h groups were up-regulated, and the value in the 12 h group was lower than that in the 6 h group. The cell apoptosis rates in the liver tissues were significantly increased in the 6 h and 12 h groups, and the value in the 12 h group was remarkably lower than that in the 6 h group (P < 0.01-0.05). Compared with the sham group, the relative expression levels of PGAM5 mRNA and protein in the mouse liver tissues in the 6 h and 12 h groups were significantly up-regulated, and the values in the 12 h group were significantly higher than those in the 6 h group (P < 0.01-0.05). The protein expression levels of PGAM5 and Caspase-1 in the liver tissues were up-regulated in the 6 h and 12 h groups. Compared with the control group, the relative expression levels of NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1 and Gasdermin D (GSDMD) proteins were up-regulated and the fluorescence intensity of GSDMD was increased in the IRI group. Compared with the IRI group, the relative expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated and the fluorescence intensity of GSDMD was considerably decreased in the inhibitor group (P < 0.01-0.05). Compared with the control group, the cell survival rate was significantly decreased, and the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly up-regulated in the siRNA-NC group (P < 0.01-0.05). Compared with the siRNA-NC group, the cell survival rate was remarkably increased, whereas the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated in the siRNA group (P < 0.01-0.05). Conclusions PGAM5 may aggravate the liver IRI in mouse models probably by mediating pyroptosis via PGAM5/Caspase-1/GSDMD signaling pathway and aggravating liver cell injury.

Objective To investigate the effect of nucleotide-binding oligomerization domaincontaining protein 1 (NOD1) on pyroptosis in hepatic ischemia-reperfusion injury.Methods An animal model of ischemia-reperfusion injury was established.Thirty healthy,male,and clean C57 BL mice were randomly divided into sham operation group (sham group) and ischemia-reperfusion group (IR,including 2 h,6 h,12 h,24 h subgroups),6 per group.Serum ALT and AST levels in each group were measured by blood biochemistry.HE staining and TUNEL were used to observe the pathological changes of liver and hepatocyte apoptosis.Immunohistochemistry was used to detect the expression and distribution of NOD1 in each group.Western blotting was used to detect NOD1,MM2,pro-Caspase-1 and active-Caspase-1 expression.NOD1 siRNA and empty control siRNA were transfected into AML12 cells,then the hypoxia/reoxygenation model was established and cells were collected to detect the expression of NOD1,AIM2 and active-Caspase-1.Results The ALT and AST levels in IR group were significantly higher than those in sham group,and peaked at IR 12-h subgroup (P＜0.05).HE staining showed that hepatic injury was the most severe at 12 h after reperfusion.TUNEL results showed that the number of apoptotic cells was the greated at 12 h after reperfusion.Western blotting showed that NOD1 protein expression was highest at 12 h after reperfusion.With the prolongation of reperfusion time,the expression of AIM2 and active-Caspase-1 gradually increased,and that of pro-Caspase-1 gradually decreased.The expression of NOD1,AIM2 and activeCaspase-1 decreased after transfection of NOD1 siRNA into AML12 cells.Conclusions NOD1 promotes liver ischemia-reperfusion injury,which may be related to NOD1 promoting liver injury by activating pyroptosis.

Objective: To acknowledge the availability and rates of annual transition of outcomes during the progression and regression stages of colorectal cancer (CRC) and related diseases, by pooling global follow-up studies on the natural history of CRC. Methods: Till March, 2017, data was collected through systematic literature review over multiple databases, including PubMed, Embase, Cochrane and Chinese Biology Medicine (CBM) disc. Information regarding the characteristics, classification system of health states, related outcomes and incidence rates on CRC or high-risk adenoma for the surveillance cohorts of the studies, were extracted and summarized. Both Meta and sensitivity analyses were performed on those outcomes if they appeared in more than 3 studies, using the random effects model. Annual transition rate with 95%CI was used to estimate each of the outcomes, Quality of the studies was assessed, using the Newcastle-Ottawa Scale. Results: A total of 29 cohort studies were included, with the mean follow-up period as 5.7 years. All studies except one, focused on adenoma-carcinoma pathway and reported the outcome parameters of adenomas by different risk, and some reported the findings on different sizes (n=6) of adenomas. These cohorts were divided into three groups (normal status, with low-risk or high-risk adenoma) according to the status of baseline endoscopic pathologic findings. Their available outcome parameters, corresponding number of involved articles, aggregated sample size and pooled annual transition rates were presented. Six parameters were obtained in the normal cohorts, including those from normal to low-risk adenoma (16 articles, 58 235, 0.030: 0.024-0.037), to high-risk adenoma (17 articles, 62 089, 0.003: 0.002-0.004), to diminutive adenoma (<5 mm, 4 articles, 1 277, 0.021: 0.013-0.029), to small adenoma (6-9 mm, 4 articles, 1 277, 0.006: 0.001-0.010), to large adenoma (≥10 mm, 7 articles, 3 531, 0.002: 0.000-0.003) and to CRC (19 articles, 104 836, 0.000 3: 0.000 2-0.000 5). Three parameters were obtained in low-risk adenoma in cohorts with polypectomy findings, including recurrence (9 articles, 4 788, 0.109: 0.062-0.157) from low-risk adenoma after polypectomy to high-risk adenoma (10 articles, 5 736, 0.009: 0.004-0.013) and to CRC (12 articles, 11 347, 0.000 6: 0.000 4-0.000 8). Three parameters were obtained on high-risk adenoma from cohorts with polypectomy findings, including recurrence (12 articles, 7 030, 0.038: 0.028-0.048) from high-risk adenoma after polypectomy to low-risk adenoma (8 articles, 2 489, 0.133: 0.081-0.185) and CRC (14 articles, 14 899, 0.002: 0.001-0.003). Except for normal to low-risk adenomas, results from the sensitivity analysis for the other parameters showed stable. Of the included studies, two presented incidence rates of CRC in different clinical stages and the another two were focusing on the parameters related to serrated pathway. Conclusions Globally, follow-up studies reported data on natural history of colorectal cancer is of paucity. Compared to the "adenoma-carcinoma" pathway, transition parameters of the serrated lesion pathway are more limited. This Meta-analysis provided convincing evidence for optimizing the strategies regarding follow-up program on the disease, using the baseline endoscopic findings from global CRC Screening Program. These results also offered strong data-related support for Chinese population- specific interventional model on colorectal cancer.

Objective To investigate the effect of miRNA-30a-3p on the proliferation,invasion and metastasis of liver cancer cells by targeting Atg3-mediated autophagy pathway.Methods The immunohistochemical staining was used to detect content of miRNA-30a-3p and Atg3 and their correlation in human hepatocellular carcinoma.Liver cancer cells were cultured in vitro and hunger environment was used to induce autophagy.RFP-GFP-LC3 double-labeled adenovirus infected hepatoma cells were used to detect autophagosomes in hepatoma cells.The expressions of autophagy-related proteins (autophagocytosis associated protein (Atg3),polyubiquitin-binding protein p62,autophagy microtubule-associated protein light chain 3 (LC3)) and EMT-related proteins (N-cadherin,vimentin,snail,ZO-1) were detected by Western blot.Platelet cloning assay and transwell assay were carried out to detect the proliferation,invasion and metastasis of carcinoma cell.CCK-8 kit was used to detect hepatocarcinoma cells' viability.Results The expression of miRNA-30a-3p was down-regulated.The expression of Atg3,E-cadherin and N-cadherin in miRNA-30a-3p high-expressed hepatocellular carcinoma was lower than that in miRNA-30a-3p low-expressed hepatocellular carcinoma.Increasing the expression of miRNA-30a-3p in hepatocellular carcinoma cells can decrease the expression of Atg3 and LC3,increase the expression of p62 and inhibit the formation of autophagosomes;otherwise,Atg3 and LC3 were increased,p62 was decreased and the formation of autophagosomes was promoted.Inhibition of Atg3 expression could decrease the expression of EMT-related proteins.When miRNA-30a-3p was inhibited,the cell viability of HCC was increased at each time point (F1 =10.314,P ＜0.05).When miRNA-30a-3p and Atg3 were inhibitor together,the cell viability of HCC was decreased at each time point(F2 =6.599,P ＜ 0.05).Conclusion miRNA-30a-3p can inhibit Atg3-mediated autophagy pathway and reduce cell autophagy activity,thus inhibiting the proliferation,invasion and metastasis of hepatocarcinoma cells.

Objective To explore the role of miR-137 in the proliferation and migration of hepatocellular carcinoma (HCC) cells by regulating Notch1 and mediating autophagy.Methods The human SMMC7721 hepatoma cell line was transfected with miR-137 mimics,miR-137 inhibitor and Notch1 interfering RNA (siRNA),and divided into normal control group (NC group),miR-137 mimics group,miR-137 inhibitor group,Notch1 siRNA group.The expression levels of miR-137 and Notch1 mRNA after the transfection were detected by RT-PCR in SMMC7721 cells.Transwell experiments were performed to analyze the effect of miR-137 and Notch1 on the migration and invasion of SMMC7721 cells.The expression levels of β-catenin and vimentin in SMMC7721 cells were detected by immunohistochemistry.The number of autophagosomes was detected by double labeled adenovirus.Western blot was utilized to detect the expression of Notch1,E-Cadherin,N-Cadherin,vimentin,P62,and LC3.Results The results of RT-PCR showed that the relative expression level of Notch1 in miR-137 inhibitor group (5.71 ± 0.45) was significantly higher than that in miR-137 mimics group (0.21 ± 0.06) with statistical significance (P ＜ 0.05).The Transwell experiments showed that there were fewer invasive metastatic hepatoma cells in miR-137 mimics group (66.00 ± 4.55) and Notch1 siRNA group (88.00 ± 6.78) than that in the miR-137 inhibitor group (515.00 ±35.12) (P ＜0.05).The expression levels of β-catenin in miR-137 mimics group and Notch1 siRNA group were significantly increased and the expression level of vimentin was decreased (P ＜ 0.05).The results of autophagy double labeled adenovirus test showed that the number of autophagosomes in miR-137 mimics group (5.50 ± 3.70) was significantly fewer than that in miR-137 inhibitor group (32.75 ± 4.11),and the difference was statistically significant (P ＜ 0.05).The expression levels of Notch1,N-cadherin,vimentin,and LC3 protein in miR-137 mimics group were much lower than that in miR-137 inhibitor group and NC group,and the expression levels of E-Cadherin and P62 protein were greatly increased.The expression level of Notch1,N-cadherin,and LC3 protein in Notch1 siRNA group were significantly lower than that in NC group,and the expression levels of E-cadherin and P62 protein were much higher than that in NC group.Conclusion MiR-137 can inhibit the proliferation,migration and invasion of HCC cells by inhibiting the expression of Notch1 and autophagy,which may become a new target for the treatment of HCC.

Angioplasty, Balloon, Coronary ; Heart Injuries ; drug therapy ; etiology ; Humans ; Thrombin ; administration & dosage

Objective To detect the apoptosis of femoral head cartilage cells and to observe the expression of apoptosis-related proteins in the tissues of the femoral head,as well as to explore the main pathway for regulating the apoptosis in steroid induced by juvenile rabbit models with avascular necrosis of femoral head.Methods The models with avascular necrosis of the femoral head and the control group model were made in New Zealand infancy albino rabbits induced by glucocorticoid(GC).The immunohistochemical method was used to detect the expressions of Caspase3,Caspase-8,apoptosis protease activating factor-1 (apaf-1),calpain-1 in the femoral heads.Results 1.The integrated optical density(IOD) values of Caspase-3 in GC-induced subgroup,the subgroup that was not induced by GC and control group were 25 142.72 ± 21 528.48,2 069.63 ± 1 096.96 and 301.80 ± 99.66,respectively.The IOD values of Caspase-8 in GC-induced subgroup,the subgroup respectively and the control group were 24 942.63 ± 18 942.99,2 016.31 ± 1 518.70,236.85 ±97.94,respectively.The IOD values of apaf-1 in GC-induced subgroup,the subgroup that was not induced by GC and the control group were 8 5 14.23 ± 6 384.20,1 118.49 ± 1 360.59,95.13 ± 38.05,respectively.The IOD values of calpain-1 in GC-induccd subgroup,the subgroup that was not induced by GC and control group were 9 636.71 ± 9 123.81,1 881.10 ± 3 277.86,126.71 ± 47.35,respectively.The IOD value differences of the Caspase-3 between GC-induced subgroup and the subgroup that was not induced by GC,the control group were extremely significant (H =l 1.470,23.996,P ＜ 0.01).The IOD value differences of the Caspase-8,apaf-1,calpain-1 between GC-induced subgroup and the control group were extremely significant (H =22.178,22.808,13.553,P ＜ 0.01).2.The linear regression analysis results showed that under the joint action of Caspase-8,apaf-1,calpain-1,only the Caspase-8 could significantly predict Caspase-3,and its regression equation regression got significant effect and could explain 40.3％ of the variance;while the regression effects of the apaf-1 and calpain-1 to Caspase-3 were not significant.Conclusion Death receptor pathway might play a major regulation role in the apoptotic process of avascular necrosis.