Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in inhibiting the formation of neutrophil extracellular traps (NETs) in mouse bone marrow neutrophils, and to analyze its pathogenic mechanism. Methods:C57BL/6 mice were injected with either wild-type (CFT073 wt) or tcpc gene-knockout UPEC CFT073(CFT073 Δ tcpc) to establish a mouse model of cystitis. Mice were sacrificed 3 d post-infection, and their bladders were collected to observe gross pathological changes. Hematoxylin-eosin (HE) staining was used to assess histopathological changes in bladder tissues, and immunohistochemistry was performed to localize TcpC in bladder tissues. Bacterial loads in urine samples were quantified using the ten-fold dilution method, and the presence of tcpc gene in genomic DNA from bladder or urine samples was confirmed by PCR. The expression of TcpC at mRNA and protein levels in mouse bone marrow nuetrophils infected with CFT073 wt was detected by qRT-PCR and Western blot. The effects of UPEC infection on expression of NETs-related proteins and the production of pro-inflammatory factors in mouse bone marrow neutrophils were analyzed by Western blot and ELISA, respectively. Reactive oxygen species(ROS) level and bacterial viability in mouse bone marrow nuetrophils were measured using ROS and bacterial viability detection kits. Results:Compared to the CFT073 Δ tcpc group, the bladder of CFT073 wt group mice exhibited significant enlargement, extensive inflammatory cell infiltration, and the presence of TcpC in bladder tissue. The bacterial load in the urine of CFT073 wt -infected mice was significantly higher than that in the CFT073 Δ tcpc group ( P<0.01). PCR confirmed the presence of the tcpc gene in bladder and urine samples from CFT073 wt-infected mice. Increased expression of TcpC at both mRNA and protein levels was observed in CFT073 wt-infected mouse bone marrow neutrophils. CFT073 wt infection inhibited the mRNA and protein expression of NETs-related proteins and reduced the production of pro-inflammatory factors in mouse bone marrow neutrophils. TcpC suppressed ROS level and promoted the survival of CFT073 wt in mouse bone marrow neutrophils. Conclusions:TcpC enhances the pathogenicity of UPEC CFT073 by inhibiting the formation and activation of NETs in mouse bone marrow neutrophils. This study provides new insights into the pathogenic mechanisms of UPEC and the immune evasion strategies of other pathogenic bacteria, as well as potential targets for clinical prevention and treatment of UPEC-induced urinary tract infections.

Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in inhibiting the formation of neutrophil extracellular traps (NETs) in mouse bone marrow neutrophils, and to analyze its pathogenic mechanism. Methods:C57BL/6 mice were injected with either wild-type (CFT073 wt) or tcpc gene-knockout UPEC CFT073(CFT073 Δ tcpc) to establish a mouse model of cystitis. Mice were sacrificed 3 d post-infection, and their bladders were collected to observe gross pathological changes. Hematoxylin-eosin (HE) staining was used to assess histopathological changes in bladder tissues, and immunohistochemistry was performed to localize TcpC in bladder tissues. Bacterial loads in urine samples were quantified using the ten-fold dilution method, and the presence of tcpc gene in genomic DNA from bladder or urine samples was confirmed by PCR. The expression of TcpC at mRNA and protein levels in mouse bone marrow nuetrophils infected with CFT073 wt was detected by qRT-PCR and Western blot. The effects of UPEC infection on expression of NETs-related proteins and the production of pro-inflammatory factors in mouse bone marrow neutrophils were analyzed by Western blot and ELISA, respectively. Reactive oxygen species(ROS) level and bacterial viability in mouse bone marrow nuetrophils were measured using ROS and bacterial viability detection kits. Results:Compared to the CFT073 Δ tcpc group, the bladder of CFT073 wt group mice exhibited significant enlargement, extensive inflammatory cell infiltration, and the presence of TcpC in bladder tissue. The bacterial load in the urine of CFT073 wt -infected mice was significantly higher than that in the CFT073 Δ tcpc group ( P<0.01). PCR confirmed the presence of the tcpc gene in bladder and urine samples from CFT073 wt-infected mice. Increased expression of TcpC at both mRNA and protein levels was observed in CFT073 wt-infected mouse bone marrow neutrophils. CFT073 wt infection inhibited the mRNA and protein expression of NETs-related proteins and reduced the production of pro-inflammatory factors in mouse bone marrow neutrophils. TcpC suppressed ROS level and promoted the survival of CFT073 wt in mouse bone marrow neutrophils. Conclusions:TcpC enhances the pathogenicity of UPEC CFT073 by inhibiting the formation and activation of NETs in mouse bone marrow neutrophils. This study provides new insights into the pathogenic mechanisms of UPEC and the immune evasion strategies of other pathogenic bacteria, as well as potential targets for clinical prevention and treatment of UPEC-induced urinary tract infections.

Objective:To develop a clinical automated diagnostic system for temporomandibular disor-ders(TMD)based on the diagnostic criteria for TMD(DC/TMD)to assist dentists in making rapid and accurate clinical diagnosis of TMD.Methods:Clinical and imaging data of 354 patients,who visited the Center for TMD & Orofacial Pain at Peking University Hospital of Stomatology from September 2023 to January 2024,were retrospectively collected.The study developed a clinical automated diagnostic system for TMD using the DC/TMD,built on the.NET Framework platform with branching statements as its in-ternal structure.Further validation of the system on consistency and diagnostic efficacy compared with DC/TMD were also explored.Diagnostic efficacy of the TMD clinical automated diagnostic system for de-generative joint diseases,disc displacement with reduction,disc displacements without reduction with limited mouth opening and disc displacement without reduction without limited mouth opening was evalua-ted and compared with a specialist in the field of TMD.Accuracy,precision,specificity and the Kappa value were assessed between the TMD clinical automated diagnostic system and the specialist.Results:Diagnoses for various TMD subtypes,including pain-related TMD(arthralgia,myalgia,headache attribu-ted to TMD)and intra-articular TMD(disc displacement with reduction,disc displacement with reduc-tion with intermittent locking,disc displacement without reduction with limited opening,disc displace-ment without reduction without limited opening,degenerative joint disease and subluxation),using the TMD clinical automated diagnostic system were completely identical to those obtained by the TMD spe-cialist based on DC/TMD.Both the system and the expert showed low sensitivity for diagnosing degenera-tive joint disease(0.24 and 0.37,respectively),but high specificity(0.96).Both methods achieved high accuracy(＞0.9)for diagnosing disc displacements with reduction and disc displacements without reduction with limited mouth opening.The sensitivity for diagnosing disc displacement without reduction without limited mouth opening was only 0.59 using the automated system,lower than the expert(0.87),while both had high specificity(0.92).The Kappa values for most TMD subtypes were close to 1,ex-cept the disc displacement without reduction without limited mouth opening,which had a Kappa value of 0.68.Conclusion:This study developed and validated a reliable clinical automated diagnostic system for TMD based on DC/TMD.The system is designed to facilitate the rapid and accurate diagnosis and classi-fication of TMD,and is expected to be an important tool in clinical scenarios.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in immune evasion, and analyze its related pathogenic mechanism. Methods:C57BL/6 mice were injected with 10 9 colony-forming unit of wild-type (CFT073 wt) or tcpc gene-knockout (CFT073 Δ tcpc) UPEC CFT073 strains from urethra into bladder to construct a mouse model of pyelonephritis. These mice were sacrificed 5 d after infection and their kidneys were taken to observe the gross pathological changes. Hematoxylin-eosin staining was used to observe histopathological changes in kidney tissues and immunohistochemistry was performed to locate TcpC in kidney tissues. The bacterial loads in urine samples of UPEC infected-mice were counted by ten-fold dilution method, and the presence of tcpc gene in the genomic DNA of bacteria from CFT073-infected mouse kidney or urine samples was measured by PCR. The expression of TcpC at mRNA level was detected by qRT-PCR after infecting dendritic cells with CFT073 wt strains. The influences of UPEC infection on the activation of NF-κB signaling pathway and the secretion of proinflammatory factors by dendritic cells were analyzed by Western blot and ELISA, respectively. The viability of UPEC strains in dendritic cells were observed by laser confocal microscope. Results:Compared with the CFT073 Δ tcpc group, the mice in the CFT073 wt group had obvious abscess in the kidneys as well as massive neutrophil infiltration and abundant TcpC in kidney tissues. The bacterial loads in the urine of CFT073 wt-infected mice were significantly higher than those in the urine of CFT073 Δ tcpc mice. PCR results showed that tcpc gene was successfully amplified from mouse kidney and urine samples. Increased expression of TcpC at both mRNA and protein levels was detected in CFT073 wt-infected dendritic cells. CFT073 wt infection inhibited the phosphorylation of NF-κB p50 and the production of proinflammatory factors in dendritic cells. TcpC promoted the survival of CFT073 wt in dendritic cells. Conclusions:TcpC expression increases significantly during CFT073 wt infection or in mice with CFT073 wt-induced pyelonephritis. It promotes the survival of CFT073 wt in dendritic cells by inhibiting the activation of NF-κB signaling pathway and reducing the secretion of pro-inflammatory cytokines. TcpC is involved in the pathogenesis of UPEC and immune evasion.

Circular RNA (circRNA) is a kind of RNA with a circular structure. The unique structure of circRNA endows it with various cell biological functions and characteristics. It has become a research hotspot recently. CircRNA can play a role via mechanisms, such as microRNA (miRNA) sponge, RNA binding protein, peptide translation and regulation of gene transcription. CircRNA was found to be associated with disc degeneration, spinal cord injury, scoliosis, and facet arthritis. Some techniques, including bioinformatics and molecular biology techniques, microarray and high-throughput sequencing, can be used to predict and to discover disease-related circRNA, aiming to evaluate whether circRNA can be used as a molecular biomarker for spinal and spinal cord diseases. Based on the current role of circRNA, the corresponding therapeutic strategies have been carried out in experimental animals, which can provide theoretical basis for gene therapy. At present, the researches in circRNA for spinal and spinal cord diseases are still insufficient compared with those in other fields. Currently, the main direction focuses on the miRNA sponge mechanism of circRNA. Due to the variety of diseases in spinal surgery, the research progress of circRNA is also varied. In addition, the development of microarray and high-throughput sequencing technology have greatly promoted the researches in circRNA. The availability of public database is of great significance in the study. The present review summarized the current researches status of circRNA in spinal and spinal cord diseases, aiming to deepen understanding of circRNA in spinal and spinal cord diseases.

Objective To evaluate the value of the prostate imaging reporting and data system version 2 (PI-RADS version 2) for the diagnosis of prostate cancer.Methods A total of 243 patients who underwent multiparametric 3T prostate MRI followed by prostate biopsy or radical prostatectomy were included.111 patients were in PSA gray zone(4.0-10.0 ng/ml).PI-RADS version 2 scores for each patient was assigned by two readers independently.Reference standard was obtained by histopathology.Positive predictive value (PPV) for prostate cancer and clinically significant cancer were compared among patients with different PI-RADS Version 2 scores using chi-square trend test.Receiver operating characteristic (ROC) curve was performed to assess diagnostic accuracy of the PI-RADS version 2 scores for prostate cancer detection,and evaluate the difference in diagnostic efficiency between transition zone and peripheral zone.Results Two hundred and eighty five suspicious foci from the 243 patients were finally recruited to this study,131 of which were diagnosed as prostate cancer according to pathology.There was significant difference in PPV for prostate cancer and clinically significant cancer among patients with different PI-RADS version 2 scores (score 1:8.0％;score 2:10.1％;score 3:49.2％;score 4:61.1％ score 5:87.9％,P＜0.01),(score 1:0;score 2:5.1％;score 3:31.1％;score 4:59.3％ score 5:88.9％,P ＜ 0.01).When PI-RADS version 2 score was 3,Youden index was maximum (0.53),the sensitivity was 92.4％ and the specificity was 61.0％.The ROC analysis revealed that the area under the curve (AUC) of prostate cancer incidence in transition zone was similar to that in peripheral zone with 0.86(95％ CI 0.78-0.95) vs.0.83(95％ CI 0.77-0.89).There were 111 patients in PSA gray zone,33 of whom were diagnosed as prostate cancer.If we used PI-RADS version 2 score 3 as the cut-off point,47 out of 111 patients would avoid unnecessary prostate biopsies with 4 misdiagnosed nonsignificant prostate cancer.Conclusions The value of PI-RADS version 2 score is positively associated with PPV for prostate cancer.PI-RADS version 2 seems to have good diagnostic accuracy in prostate cancer detection.Clinical application of PI-RADS version 2 may help to reduce the number of unnecessary biopsy.

For attracting more social charity funding into the health field, in-depth interviews are conducted into four health foundations in Beijing, presenting three aspects of existing problems and obstacles in the foundations devel-opment in this article. Firstly, the foundations have low effect in fundraising, poor information publication, little com-munication between other facilities and vague mechanism in donation. Secondly, the social public has erroneous views leading to deviant behavior. Finally, some annual inspection standards of the foundation are not suitable for the health field. Based on the above analysis, suggestions about how to improve transparency and fundraising ability in foundations and change the public erroneous views in donation are proposed. The governments might be suggested to get more relax-ed on the annual inspection standards of the foundations, and build an information platform in healthcare field as well.

Object Under the premise of protecting periodicals published in Republic of China, these periodicals were processed with digitalization for the purpose of being utilized in a easy way. Methods Oracle 9i database software was used to establish database table structure. Periodicals published in Republic of China were selected, periodicals pictures were processed and the literature subjects were indexed before databases retrieval system of these periodicals was made and published. Results A full text data base retrieval system containing 20 kinds of periodicals published in Republic of China was established, to provide both retrieval from multi-angles and picture browsing of the full text. Conclusion Digitalization technique is a way of reproducible protection and utilization of periodicals published in Republic of China.