Objective:To investigate the clinical value of multiparameteric quantitative ultrasound combined with a non-invasive prediction model for assessing high-risk steatohepatitis.Methods:One hundred and ninety-four cases with metabolic-associated fatty liver disease (MAFLD) who underwent liver biopsy in Huashan Hospital, Fudan University, from June 2021 to September 2022 were selected. Shear wave elastography (SWE), shear wave dispersion (SWD) imaging, and attenuation imaging (ATI) examinations were conducted in all patients before biopsy. High-risk steatohepatitis was defined as a total activity score of ≥4 in patients with steatohepatitis, hepatocellular ballooning, and liver lobular inflammation based on pathological hepatic steatosis, inflammatory activity, and fibrosis scoring system (SAF), and fibrosis stage≥F2. Binary logistic regression analysis was used to identify the factors influencing high-risk steatohepatitis. A predictive model for diagnosing high-risk steatohepatitis was constructed using R language. The DeLong test was used to compare the area under the curve between groups. Measurement data was compared between groups using the t-test or rank-sum test, and count data were compared between groups using the χ2 test. Results:There were 46 cases (23.7%) with high-risk steatohepatitis. The quantitative ultrasound parameters included elastic modulus ( OR=2.958, 95% CI: 1.889-4.883, P<0.001), dispersion coefficient ( OR=1.786, 95% CI: 1.424-2.292, P<0.001) and attenuation coefficient ( OR=42.642, 95% CI: 3.463-640.451, P=0.004). Serological indexes of fasting blood glucose ( OR=1.196, 95% CI: 1.048-1.392, P=0.011), alanine aminotransferase ( OR=1.012, 95% CI: 1.006-1.019, P<0.001), aspartate aminotransferase ( OR=1.027, 95% CI: 1.014-1.042, P<0.001), γ-glutamyl transferase ( OR=1.008, 95% CI: 1.001-1.017, P=0.041) and HDL cholesterol ( OR=0.087, 95% CI: 0.016-0.404, P=0.003) were the factors influencing its progression. The AUCs of elastic modulus, dispersion coefficient, attenuation coefficient, multiparametric ultrasound model, serological index model, and ultrasound combined with serology model for the diagnosis of high-risk steatohepatitis were 0.764, 0.758, 0.634, 0.786, 0.773 and 0.825, respectively. The results of the DeLong test showed that the ultrasound combined with the serological model was significantly better than the serological index model and the elastic modulus, dispersion coefficient, and attenuation coefficient alone ( P=0.024, 0.027, 0.038 and <0.001). Conclusion:The combination of multiparametric quantitative ultrasound is helpful for the non-invasive diagnosis of high-risk steatohepatitis and possesses great clinical significance.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective In this study,Knoevenagel derivatives of curcumin were synthesized,and their oil-water partition coefficient were determined.Our aim is to provide an experimental basis for further development of curcumin derivatives.Methods Two Knoevenagel derivatives of curcumin,including 4-(thiophen-2-ylidene)curcumin(3a)and 4-(pyridine-4-ylidene)curcumin(3b),were obtained by using the methylene group of curcumin as the modification site and purified by column chromatography.The structures of these derivatives were confirmed by nuclear magnetic resonance spectroscopy(NMR),infrared(IR)and high-resolution liquid mass spectrometry(HRLC-MS).The oil-water partition coefficient of the derivatives in n-octanol aqueous solution was determined by quantitative analysis using HPLC.Results Knoevenagel derivatives of curcumin were successfully synthesis.The oil-water partition coefficients(lgPap)of curcumin derivatives 3a and 3b are 0.96 and 0.82,respectively.Compared with the oil-water partition coefficient of curcumin(lgPap=3.85),it suggested that curcumin derivatives showed better water solubility than curcumin.Conclusion Compared to the curcumin prototype,Knoevenagel derivatives of curcumin increased water solubility and improved bioavailability.Thus,it may provide experimental basis for introducing heteroarylene moiety of the methylene position of curcumin to enhance pharmacological activity.

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway, as an important part of the innate immune system, is the main pathway for cytoplasmic DNA recognition and cGAS can be triggered by a variety of cytoplasmic dsDNA. This pathway has become an important bridge connecting autoimmunity, aseptic inflammatory response and cell aging. In recent years, cGAS-STING pathway has attracted increasing attention in autoimmune diseases. In rheumatoid arthritis (RA), neutrophil extracellular traps (NETs) induce typeⅠ interferon response and accelerate the production of anti-citrullinated peptide antibody (ACPA) through the cGAS-STING pathway. In addition, the cGAS-STING pathway also participates in synovitis, bone destruction and RA progression by promoting the proliferation and activation of fibroblast-like synovitis cells and the polarization of M1 macrophages. Inhibition of the cGAS-STING pathway or its downstream signaling pathway can reduce synovial inflammation in RA, suggesting that cGAS-STING pathway may be a potential therapeutic target for RA.

Objective:To explore the mechanism of social support and self-efficacy in rehabilitation exercise in the relationship between psychological resilience and kinesiophobia in hip fracture patients.Methods:Totally 284 hip fracture patients treated at the Department of Trauma and Orthopedics, Binzhou Medical University Hospital from May 2022 to April 2023 were selected by convenience sampling. Data were collected using the general information questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), the Social Support Rating Scale (SSRS), the Self-Efficacy Rehabilitation Outcome Scale (SER), and the Tampa Scale for Kinesiophobia (TSK). Process 4.1 was used for chain mediation effect analysis.Results:The scores for the 284 hip fracture patients were as follows: CD-RISC (58.72±7.77), SSRS (29.70±5.11), SER (91.23±8.41), and TSK (38.07±3.65). Psychological resilience, social support, self-efficacy in rehabilitation exercise, and kinesiophobia were all significantly correlated pairwise (all P<0.01). Social support and self-efficacy in rehabilitation exercise had a chain mediation effect between psychological resilience and kinesiophobia, with mediation effect values of -0.020 and -0.079, accounting for 17.52% and 67.70% of the total effect, respectively. Conclusions:Psychological resilience directly influences the level of kinesiophobia in hip fracture patients and has an indirect effect through the chain mediation of social support and self-efficacy in rehabilitation exercise.

Purpose To evaluate the value of real-time contrast-enhanced ultrasound (CEUS) combined with comparative observation in determining the initial time of peripheral lung lesion,and to provide a new method for the diagnosis of peripheral lung disease by CEUS.Materials and Methods Sixty patients with peripheral lung disease diagnosed by chest X-ray or CT examination were examined by CEUS,and the lesions and perfusion of surrounding lung tissue were observed in real time and comparatively.The time of initial enhancement of peripheral lung lesion was determined by real-time comparative observation method,that is,to compare the time of contrast agent to reach the peripheral lung lesion with the time to reach the adjacent gas-containing lung tissue.All lesion specimens were obtained by surgery or ultrasound-guided percutaneous biopsy,and the pathological diagnosis was performed.According to the pathological results,the peripheral lung lesions were classified into the malignant group,the chronic inflammation group and the pneumonia group.Results Sixty cases of peripheral lung lesions were identified as 38 cases of malignant tumors (including 15 cases ofsquamous cell carcinomas,9 cases of adenocarcinoma cell carcinomas,2 cases of large cell carcinomas,9 cases of small cell carcinomas and 3 cases of metastatic carcinomas),14 cases of chronic inflammation lesions (including 7 cases of tuberculomas,3 cases of inflammatory pseudotumors and 4 cases of lung abscess) and 8 cases of pneumonia.The detection rates of pulmonary arterial phase and bronchial artery phase using the real-time comparative observation method were 100％ (60/60) and 85％ (51/60),respectively.The initial time of pulmonary arterial phase and bronchial artery phase were (6.1 ± 0.9) s and (10.5 ± 1.6) s,respectively.The initial time of pulmonary arterial phase was sooner than bronchial artery phase,the difference was statistical significance (P＜0.05).Conclusion The real-time CEUS combined with comparative observation method has important diagnostic value in judging the initial enhancement time of peripheral lung lesion and can provide a new method for the accurate diagnosis of peripheral lung disease,which is worth popularizing.

Objective To explore the effects of bundle care on preventing cannula dislocation for tracheotomy in patients with inhalation injury. Methods Totally 51 patients who received tracheotomy in the First Affiliated Hospital of PLA General Hospital between January 2010 and December 2014 were selected as a control group, while another 36 patients with inhalation injury who were admitted and received tracheotomy from January 2015 to May 2017 were selected as an observation group. Patients in the control group received conventional nursing after tracheotomy, while patients in the observation group received safely managed bundle care on the basis of conventional nursing. The incidence of unanticipated cannula dislocation after tracheotomy and before extubation were then observed between the patients in the two groups. Results The incidence of unanticipated cannula dislocation of the patients in the observation group and the control group was 2.8% (1/36) and 19.6% (10/51), respectively (χ2=5.412,P< 0.05). Conclusions Bundle care, when applied in the management of cannula for tracheotomy in patients with inhalation injury, can reduce the incidence of unanticipated cannula dislocation.

Objective To evaluate the association between C-reactive protein (CRP) blood levels and specific survival time of non-small cell lung cancer (NSCLC) patients treated with chemotherapy.Methods Data from 96 advanced (stage ⅢB/Ⅳ) NSCLC patients were analyzed.All patients were divided into two groups based on the enrolled time as follows the initial treatment group (48 cases) and retreatment group (48 cases).According to 0.6 mg/L and 7.3 mg/L of CRP which were the 1/3 and 2/3 of CRP concentrations,respectively,the 96 patients were divided into low,intermediate and high groups.Kaplan-Meier and Cox proportional-hazard models were used to evaluate the relationship between the CRP level and survival time.Results After adjusting for age,sex,smoking history,histological type and stage of lung cancer,a significant relationship between CRP and survival time was observed (P ＜ 0.05).Such significant differences of survival time were also observed in both of the adenocarcinoma (P ＜ 0.001) and squamous with poorly differentiated (P =0.032) subtypes.On stratification analysis by chemotherapy status,the circulating CRP level in retreatment group was correlated well with survival time (P ＜ 0.001).However,the influence of circulating CRP levels on survival time in initial group did not reach statistical significance (P =0.296).For all patients,the hazard ratio with high CRP levels for NSCLC-specific survival was 1.15 (95 ％ CI 0.82-1.61) compared with that of low CRP levels.The hazard ratio for the initial treatment group and retreatment group were 0.52 (95 ％ CI 0.16-1.74) and 1.77 (95 ％ CI 0.73-4.26),respectively.Patients with high circulating CRP level also responded poorly to chemotherapy.Conclusion A high level of circulating CRP is associated with an inferior response and survival outcome in NSCLC patients treated with chemotherapy.

Echinomycin is a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1alpha-mediated endothelin (ET)-2 expressions contributed to ovarian ovulation in response to human chorionic gonadotropin (hCG) during gonadotropin-induced superuvulation. By real-time RT-PCR analysis, ET-2 mRNA level was found to significantly decrease in the ovaries after echinomycin treatment, while HIF-1alpha mRNA and protein expression was not obviously changed. Further analysis also showed that these changes of ET-2 mRNA were consistent with HIF-1 activity in the ovaires, which is similar with HIF-1alpha and ET-2 expression in the granulosa cells with gonadotropin and echinomycin treatments. The results of HIF-1alpha and ET-2 expression in the granulosa cells transfected with cis-element oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF-1alpha directly mediated the transcriptional activation of ET-2 during gonadotropin-induced superuvulation. Taken together, these results demonstrated that HIF-1alpha-mediated ET-2 transcriptional activation is one of the important mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.
Animals ; Cells, Cultured ; Chorionic Gonadotropin/*pharmacology ; Echinomycin/*pharmacology ; Endothelin-2/genetics/*metabolism ; Female ; Gonadotropins, Equine/*pharmacology ; Granulosa Cells/drug effects/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/genetics/metabolism/physiology ; Oligonucleotides/genetics ; Ovary/cytology/drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Superovulation/*drug effects ; Transcriptional Activation