ObjectiveTo investigate the effect of bone morphogenetic protein 3 （BMP3） on the expression of inflammatory factors and joint damage in adjuvant arthritis （AA） induced by Freund′s complete adjuvant （FCA） in rats. MethodsThe AIA model was established in SD rats by intradermal injection of FCA into the toes of the left hind limb， and BMP3 overexpressing adenovirus （Ad-BMP3） or control adenovirus （Ad-NC） was injected in situ into the knee joint cavity on day 8 after modeling. Subsequently， HE staining was used to observe the histopathological changes in the synovium， immunohistochemistry was used to detect the expression of BMP3 in the synovium， and ELISA was used to analyze the expression levels of IL-6， IL-1β and TNF-α in the serum. Primary fibroblast-like synoviocytes （FLS） were isolated from AIA rats， the expression of BMP3 in FLS was knocked down or overexpressed， and Western blot and qRT-PCR were used to detect the expression levels of BMP3 and inflammatory factors in FLS. ResultsHE staining confirmed the successful establishment of the AIA model. Compared with normal rats， AIA rats showed decreased BMP3 expression in synovial tissue. Knockdown of BMP3 promoted the protein expression of inflammatory factors （IL-6， IL-1β， IL-17A， TNF-α） and the mRNA expression of chemokines ［C-C motif chemokine ligand 2 （CCL2）， C-C motif chemokine ligand 3 （CCL3）， Vascular Cell Adhesion Molecule-1 （VCAM-1）］ in FLS. In contrast， overexpression of BMP3 suppressed the expression of these inflammatory factors and chemokines. Intra-articular injection of BMP3-overexpressing adenovirus in AIA rats upregulated BMP3 expression in synovial tissue and inhibited synovial inflammation and bone erosion. ConclusionBMP3 suppresses the production of inflammatory factors and chemokines in FLS， thereby alleviating synovial hyperplasia and bone erosion in arthritis.

OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

Objective:To verify and compare the correlation and diagnostic efficacy of international bowel ultrasound segmental activity score（IBUS-SAS），bowel ultrasound score（BUSS），simple ultrasound score for Crohn's disease（SUS-CD），and simple ultrasound score（Simple-US）with endoscopic disease activity in Crohn's disease（CD）patients. To provide external validation of the diagnostic efficacy of intestinal ultrasound（IUS）score and theoretical basis for clinical selection of optimal IUS score.Methods:A total of 160 patients with clinical diagnosis of CD combined with IUS and intestinal endoscopy were retrospectively analyzed in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2022 to August 2024. IUS parameters were measured and scored with IBUS-SAS，SUS-CD，BUSS and Simple-US scores. Endoscopic SES-CD was used to evaluate intestinal disease activity in patients without history of intestinal resection，and Rutgeerts score was used to evaluate intestinal disease activity in patients with history of intestinal resection. Endoscopic remission in patients with CD was defined as SES-CD < 3 or Rutgeerts score i0 and i1，mild endoscopic disease activity was defined as 7 > SES-CD≥3 or Rutgeerts score = 2，moderate endoscopic disease activity was defined as 15 > SES-CD≥7 or Rutgeerts score i3，severe endoscopic disease activity was defined as SES-CD≥15 or Rutgeerts i4. The correlation and diagnostic efficacy of IBUS-SAS，SUS-CD，BUSS and Simple-US scores with endoscopic disease activity in patients with CD were compared and analyzed.Results:IUS scores including IBUS-SAS，SUS-CD，BUSS and Simple-US were significantly correlated with endoscopic intestinal disease activity，SES-CD and Rutgeerts scores in CD patients（ r s = 0.706，0.492，0.502，0.526；0.825，0.581，0.584，0.603；0.541，0.434，0.437，0.467；all P＜0.05）. Among them，IBUS-SAS showed better correlation than the other three IUS scores. ROC curve showed that IBUS-SAS，SUS-CD，BUSS，and Simple-US had high predictive values for endoscopic disease activity and endoscopic disease moderate-severe activity in patients with CD（AUC = 0.886，0.748，0.730，0.756；all P＜0.05）. The diagnostic efficacy of IBUS-SAS on the presence of endoscopic disease activity in patients with CD was significantly higher than those of the other three IUS scores . Conclusions:IBUS-SAS，SUS-CD，BUSS and Simple-US are significantly correlated with the endoscopic results of on intestinal disease activity of CD，and have high predictive values for intestinal disease activity status，among which IBUS-SAS is superior to the other three IUS scores. It is recommended that IBUS-SAS be used first to evaluate intestinal disease activity in patients with CD.

Objective:To investigate the development and job adaptability of specialized nurses in Liaoning Province, and to provide basis for further improving the job adaptability of specialized nurses.Methods:In August 2024, provincial-level or above specialized nurses from secondary and above hospitals in 14 cities of Liaoning Province were selected by convenient sampling method, and their job adaptation was investigated using General Information Questionnaire and Workers' Job Adaptation Scale to conduct cross-sectional research.Results:A total of 3 460 valid questionnaires were collected. Among the 3 460 specialized nurses, tertiary hospitals accounted for 91.01% (3 149/3 460), undergraduates accounted for 89.28% (3 089/3 460), and 51.13% (1 769/3 460) were aged from 36 to 45. The top three training specialties for specialized nurses were severe illness, operating room and intravenous infusion therapy, and the training duration was mostly 6 to 12 weeks, accounting for 58.70% (2 031/3 460). After training, they mostly engaged in specialized disease care/case care, accounting for 86.07% (2 978/3 460); In terms of hospital security, 71.16% (2 462/3 460) of the specialized nurses said that the working conditions provided by the hospital could meet their work needs, 43.93% (1 520/3 460) said that the hospital performance was reasonable, 43.29% (1 498/3 460) said that there were sufficient promotion opportunities, and 49.28% (1 705/3 460) said that the hospital has dedicated positions for specialized nurses. The score of the Job Fit Scale for Professional Nurses was (37.36 ± 6.30) points, including the attribute fit dimension (12.45 ± 2.32) points, the demand-supply fit dimension (11.84 ± 2.57) points and the ability-requirement fit dimension (13.06 ± 2.12) points.Conclusions:The post adaptability of provincial-level or above specialized nurses in Liaoning province is in the high level, but the distribution of specialized nurses is uneven, and the proportion of secondary hospitals is low. The training mechanism for specialized nurses has gradually matured, but some of them are not fully played, and there is little participation in scientific research and innovation activities after training. Therefore, it is suggested that in the future work, secondary hospitals should be encouraged to select nursing backbones according to their needs to participate in specialized training programs to improve nurses' professional skills; Nursing managers encourage specialized nurses to consciously participate in systematic scientific research training to enhance their nursing scientific research ability; rational use of specialist nurses in hospitals, giving full play to their professional advantages, and promoting the development of specialties.

Objective:To investigate the development and job adaptability of specialized nurses in Liaoning Province, and to provide basis for further improving the job adaptability of specialized nurses.Methods:In August 2024, provincial-level or above specialized nurses from secondary and above hospitals in 14 cities of Liaoning Province were selected by convenient sampling method, and their job adaptation was investigated using General Information Questionnaire and Workers' Job Adaptation Scale to conduct cross-sectional research.Results:A total of 3 460 valid questionnaires were collected. Among the 3 460 specialized nurses, tertiary hospitals accounted for 91.01% (3 149/3 460), undergraduates accounted for 89.28% (3 089/3 460), and 51.13% (1 769/3 460) were aged from 36 to 45. The top three training specialties for specialized nurses were severe illness, operating room and intravenous infusion therapy, and the training duration was mostly 6 to 12 weeks, accounting for 58.70% (2 031/3 460). After training, they mostly engaged in specialized disease care/case care, accounting for 86.07% (2 978/3 460); In terms of hospital security, 71.16% (2 462/3 460) of the specialized nurses said that the working conditions provided by the hospital could meet their work needs, 43.93% (1 520/3 460) said that the hospital performance was reasonable, 43.29% (1 498/3 460) said that there were sufficient promotion opportunities, and 49.28% (1 705/3 460) said that the hospital has dedicated positions for specialized nurses. The score of the Job Fit Scale for Professional Nurses was (37.36 ± 6.30) points, including the attribute fit dimension (12.45 ± 2.32) points, the demand-supply fit dimension (11.84 ± 2.57) points and the ability-requirement fit dimension (13.06 ± 2.12) points.Conclusions:The post adaptability of provincial-level or above specialized nurses in Liaoning province is in the high level, but the distribution of specialized nurses is uneven, and the proportion of secondary hospitals is low. The training mechanism for specialized nurses has gradually matured, but some of them are not fully played, and there is little participation in scientific research and innovation activities after training. Therefore, it is suggested that in the future work, secondary hospitals should be encouraged to select nursing backbones according to their needs to participate in specialized training programs to improve nurses' professional skills; Nursing managers encourage specialized nurses to consciously participate in systematic scientific research training to enhance their nursing scientific research ability; rational use of specialist nurses in hospitals, giving full play to their professional advantages, and promoting the development of specialties.

Objective:To verify and compare the correlation and diagnostic efficacy of international bowel ultrasound segmental activity score（IBUS-SAS），bowel ultrasound score（BUSS），simple ultrasound score for Crohn's disease（SUS-CD），and simple ultrasound score（Simple-US）with endoscopic disease activity in Crohn's disease（CD）patients. To provide external validation of the diagnostic efficacy of intestinal ultrasound（IUS）score and theoretical basis for clinical selection of optimal IUS score.Methods:A total of 160 patients with clinical diagnosis of CD combined with IUS and intestinal endoscopy were retrospectively analyzed in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2022 to August 2024. IUS parameters were measured and scored with IBUS-SAS，SUS-CD，BUSS and Simple-US scores. Endoscopic SES-CD was used to evaluate intestinal disease activity in patients without history of intestinal resection，and Rutgeerts score was used to evaluate intestinal disease activity in patients with history of intestinal resection. Endoscopic remission in patients with CD was defined as SES-CD < 3 or Rutgeerts score i0 and i1，mild endoscopic disease activity was defined as 7 > SES-CD≥3 or Rutgeerts score = 2，moderate endoscopic disease activity was defined as 15 > SES-CD≥7 or Rutgeerts score i3，severe endoscopic disease activity was defined as SES-CD≥15 or Rutgeerts i4. The correlation and diagnostic efficacy of IBUS-SAS，SUS-CD，BUSS and Simple-US scores with endoscopic disease activity in patients with CD were compared and analyzed.Results:IUS scores including IBUS-SAS，SUS-CD，BUSS and Simple-US were significantly correlated with endoscopic intestinal disease activity，SES-CD and Rutgeerts scores in CD patients（ r s = 0.706，0.492，0.502，0.526；0.825，0.581，0.584，0.603；0.541，0.434，0.437，0.467；all P＜0.05）. Among them，IBUS-SAS showed better correlation than the other three IUS scores. ROC curve showed that IBUS-SAS，SUS-CD，BUSS，and Simple-US had high predictive values for endoscopic disease activity and endoscopic disease moderate-severe activity in patients with CD（AUC = 0.886，0.748，0.730，0.756；all P＜0.05）. The diagnostic efficacy of IBUS-SAS on the presence of endoscopic disease activity in patients with CD was significantly higher than those of the other three IUS scores . Conclusions:IBUS-SAS，SUS-CD，BUSS and Simple-US are significantly correlated with the endoscopic results of on intestinal disease activity of CD，and have high predictive values for intestinal disease activity status，among which IBUS-SAS is superior to the other three IUS scores. It is recommended that IBUS-SAS be used first to evaluate intestinal disease activity in patients with CD.

Objective To explore the activation of tumor necrosis factor-α(TNF-α)signaling pathway and the expressions of the associated inflammatory factors in NPHP1-defective renal tubular epithelial cells.Methods A human proximal renal tubular cell(HK2)model of lentivirus-mediated NPHP1 knockdown(NPHP1KD)was constructed,and the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors CXCL5,CCL20,IL-1β,IL-6 and MCP-1 were detected using RT-qPCR,Western blotting or enzyme-linked immunosorbent assay.A small interfering RNA(siRNA)was transfected in wild-type and NPHP1KDHK2 cells,and the changes in the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors were examined.Results NPHP1KDHK2 cells showed significantly increased mRNA expressions of TNF-α,C/EBPβ,CXCL5,IL-1β,and IL-6(P<0.05),protein expressions of phospho-p38 and C/EBPβ(P<0.05),and IL-6 level in the culture supernatant(P<0.05),and these changes were significantly blocked by transfection of cells with siRNA-C/EBPβ(P<0.05).Conclusion TNF-α signaling pathway is activated and its associated inflammatory factors are upregulated in NPHP1KDHK2 cells,and C/EBPβ may serve as a key transcription factor to mediate these changes.

Objective To explore the activation of tumor necrosis factor-α(TNF-α)signaling pathway and the expressions of the associated inflammatory factors in NPHP1-defective renal tubular epithelial cells.Methods A human proximal renal tubular cell(HK2)model of lentivirus-mediated NPHP1 knockdown(NPHP1KD)was constructed,and the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors CXCL5,CCL20,IL-1β,IL-6 and MCP-1 were detected using RT-qPCR,Western blotting or enzyme-linked immunosorbent assay.A small interfering RNA(siRNA)was transfected in wild-type and NPHP1KDHK2 cells,and the changes in the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors were examined.Results NPHP1KDHK2 cells showed significantly increased mRNA expressions of TNF-α,C/EBPβ,CXCL5,IL-1β,and IL-6(P<0.05),protein expressions of phospho-p38 and C/EBPβ(P<0.05),and IL-6 level in the culture supernatant(P<0.05),and these changes were significantly blocked by transfection of cells with siRNA-C/EBPβ(P<0.05).Conclusion TNF-α signaling pathway is activated and its associated inflammatory factors are upregulated in NPHP1KDHK2 cells,and C/EBPβ may serve as a key transcription factor to mediate these changes.

OBJECTIVETo explore the differential characteristics of the AMA-M2 autoantibody in patients with primary biliary cirrhosis (PBC) and non-PBC patients.

METHODSPatients with abnormal liver function at the Capital Medical University affiliated to Beijing You-an Hospital were enrolled in this study between January 2011 and December 2013. Serum levels of ANA, AMA and AMA-M2 were detected by indirect fluorescence assay and enzyme-linked immunosorbent assay. The patients' clinical data was obtained for retrospective analysis. Statistical analyses were performed using the SPSS 16.0 software. Enumeration data have been presented as numbers and percentages, and were analyzed using the chi-square test and one-way ANOVA test.

RESULTSOf the 5315 patients with abnormal liver function, 15.3% (811/5315) were AMA-M2 positive patients; among those 811 patients, 78.4% (636) had PBC, 4.4% (36) had PBC overlapping with autoimmune hepatitis (AIH), 4.4% (36) had drug-induced liver injury, 6.5% (53) had hepatitis B, 3.3% (27) had hepatitis C, 0.6% (5) had hepatitis E, 0.9% (7) had alcoholic liver disease, 0.5% (4) had non-alcoholic fatty liver, 0.8% (6) had primary hepatic carcinoma, and 0.1% (1) had infectious mononucleosis. Serum AMA-M2 level was significantly higher in the PBC patients (vs. other groups, P less than 0.001) with the exception of the patients with PBC/AIH overlap syndrome. Among the 811 patients with AMA-M2 positivity, 88.5% (718) showed AMA positivity and 91.1% (739) showed ANA positivity. Serum alanine transferase (ALT) and aspartate transferase (AST) levels were significantly higher in the drag-induced liver injury patients (527.74+/-684.65 U/L, 490.60+/-716.89 U/L) and the hepatitis E patients (1015.94 ± 165.55 U/L, 665.4 ± 297.14 U/L) than in the PBC patients (96.02 ± 115.56 U/L, 94.82 ± 83.32 U/L) (ALT: F =8.041, P < 0.001, P < 0.001; AST: F =8.066, P < 0.001, P < 0.001). Serum alkaline phosphatase (ALP; 265.16 ± 179.08 U/L) and glutamyl transferase (GGT; 332.02 ± 279.29 U/L) were significantly higher in the PBC patients than in the hepatitis B patients (135.35 ± 123.17 U/L, 140.27 ± 229.24 U/L) and the hepatitis C patients (85.65 ± 27.77 U/L, 92.70 ± 125.72 U/L) (ALP: F=3.911, P =0.01, P=0.001; GGT: F=4.081, P <0.001, P < 0.001). The serum IgM level was significantly higher in the PBC patients (4.60 ± 2.67 g/L) than in the patients with drug-induced liver injury (1.76 ± 1.15 g/L), hepatitis B (2.02 ± 1.41 g/L), hepatitis C (1.48 ± 0.92 g/L), hepatitis E (1.40 ± 0.68 g/L), alcoholic liver disease (1.57 ± 1.07 g/L), non-alcoholic fatty liver (1.05 ± 0.72 g/L), and primary hepatic carcinoma (2.64 ± 2.26 g/L) (F=16.83, P < 0.001, P < 0.001, Probability value < 0.001, Probability value < 0.05, Probability value < 0.01, Probability value < 0.05 respectively).

CONCLUSIONAlthough detection of serum AMA-M2 is an important feature of PBC diagnostic testing,there is a high ratio of serum AMA-M2 detected in patients with drug-induced liver injury, hepatitis B, C and E, alcoholic liver disease, non-alcoholic fatty liver,and primary hepatic carcinoma. The AMA-M2 positive non-PBC patients still require close observation to watch for future development of PBC.

Autoantibodies ; Beijing ; Carcinoma, Hepatocellular ; Chemical and Drug Induced Liver Injury ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B ; Hepatitis C ; Hepatitis, Autoimmune ; Humans ; Liver Cirrhosis, Biliary ; Liver Diseases, Alcoholic ; Liver Function Tests ; Liver Neoplasms ; Retrospective Studies