BACKGROUND:High-grade serous ovarian cancer (HGSOC) remains a leading cause of gynecologic cancer mortality, with heterogeneous clinical outcomes necessitating improved prognostic models. This study aimed to develop and validate a comprehensive survival prediction model integrating traditional clinicopathological factors with novel molecular and coagulation parameters. METHODS:We retrospectively analyzed 216 HGSOC patients treated between 2012 and 2017. A comprehensive machine learning framework incorporating 88 algorithms was developed to predict survival outcomes, integrating conventional prognostic factors with coagulation parameters, particularly D-dimer levels. Model performance was evaluated using time-dependent AUC, concordance index, and calibration curves. External validation was performed using an independent cohort of 108 patients from three institutions. RESULTS:The machine learning model demonstrated excellent discriminative capability (AUC 0.771, 95% CI 0.709-0.832), with improving predictive accuracy from 1-year to 5-year follow-up. Multivariate analysis identified five independent prognostic factors: p53 expression, lymphadenectomy, TNM stage, hypercoagulability, and Ki67 expression. The model showed robust performance in external validation. CONCLUSIONS:Our novel machine learning-based survival prediction model demonstrates superior prognostic accuracy and temporal stability compared to conventional approaches. The integration of coagulation parameters provides new insights into disease progression. This model could facilitate personalized treatment decisions in clinical practice, though further prospective validation is warranted.

BackgroundIn the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach.MethodsBetween April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts.ResultsOur investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%–8.0% range, and were highest in 45–54-year olds. When compared with 35–44-or 45–54-year olds, HPV prevalence was highest in 55–64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35–44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7–100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3–82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45–54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55–64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7–100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0–80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771–0.920] vs. 0.812 [95% CI: 0.734–0.891], P = 0.236).ConclusionsPrimary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35–44 and 55–64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35–44 year old females.

IntroductionSentinel lymph node (SLN) biopsy has long been considered as an alternative for pelvic lymphadenectomy in cervical cancer. However, the optimal strategy for applying SLN biopsy in cervical cancer remains lacking.MethodsWe are performing a multicenter, randomized controlled trial to compare the two approaches for lymph node dissection in cervix cancer (PHENIX trial, ClinicalTrials.gov number, NCT02642471). We enroll patients with FIGO 2018 stage IA1 (lymphovascular space involvement), IA2, IB1, IB2 and IIA1 cervical squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma. SLN biopsy were performed at the start of surgery. The SLNs were submitted for frozen section examination and patients were triaged into the PHENIX-I (SLN-negative) or PHENIX-II (SLN-positive) cohort. In each cohort, patients were randomized in a 1:1 ratio into the experimental (SLN biopsy alone) or reference (pelvic lymphadenectomy) arm. This trial was designed with non-inferiority hypothesis and the primary endpoint is disease-free survival. Estimated sample sizes of 830 and 250 are required to fulfill the study objectives of PHENIX-I and II, respectively.Current Trial StatusUp to June 2023, 826 and 67 patients enrolled PHENIX-I and PHENIX-II cohort, respectively. Twenty-five patients were excluded due to inappropriate postoperative pathology. Among the current data, the bilateral detecting rate of SLN was 82.4%. The frozen section examination was found false-negative in 7 patients and false-positive in 3. Adjuvant therapies were administered in 47.9% patients with pathological risks. The median follow-up time reached 30 months. Neither of the cohorts showed difference in disease-free survival between the arms. The final presentation of results is expected in 2026.

Abstract Although many studies have uncovered an important role for the receptor-binding protein kinase RIP1 in controlling cell death signaling, its possible contributions to cancer pathogenesis have been little explored. Here, we report that RIP1 functions as an oncogenic driver in human melanoma. Although RIP1 was commonly upregulated in melanoma, RIP1 silencing inhibited melanoma cell proliferation in vitro and retarded the growth of melanoma xenografts in vivo. Conversely, while inducing apoptosis in a small proportion of melanoma cells, RIP1 overexpression enhanced proliferation in the remaining cells. Mechanistic investigations revealed that the proliferative effects of RIP1 overexpression were mediated by NF-κB activation. Strikingly, ectopic expression of RIP1 enhanced the proliferation of primary melanocytes, triggering their anchorage-independent cell growth in an NF-κB–dependent manner. We identified DNA copy-number gain and constitutive ubiquitination by a TNFα autocrine loop mechanism as two mechanisms of RIP1 upregulation in human melanomas. Collectively, our findings define RIP1 as an oncogenic driver in melanoma, with potential implications for targeting its NF-κB–dependent activation mechanism as a novel approach to treat this disease. Cancer Res; 75(8); 1736–48. ©2015 AACR.

<p>Supplementary Figs. S1-S8 and Table S1 Supplementary Materials and Methods - The primers used for qPCR. Supplementary Fig. S1. Quantitation of RIP1 expression in melanocytic tumors. Supplementary Fig. S2. Melanocytes of different origins express lower levels of RIP1 than melanoma cells. Supplementary Fig. S3. Overexpression of RIP1 triggers cell death independently of its kinase domain. Supplementary Fig. S4. NF-kB is constitutively activated in melanoma cells. Supplementary Fig. S5. RIP1 overexpression triggers moderate reduction in melanocyte viability independently of caspases. Supplementary Fig. S6. RIP1 mRNA expression and its gene copy number variations in fresh melanoma isolates. Supplementary Fig. S7. The turnover rates of RIP1 mRNA are comparable between melanoma cells and melanocytes. Supplementary Fig. S8. Overexpression of RIP1 reverses reduction in NF-kB activation and melanoma cell proliferation caused by knockdown of TNFR1. Supplementary Table S1. Summary of melanocytic tumors and their expression levels of RIP1.</p>

Supplementary Experimental Procedures

This study aimed to explore the clinical significance of detection of human papillomavirus (HPV) DNA and E6/E7 mRNA for cervical cancer patients. For this purpose, a total of 300 patients with cervical lesions who performed the colposcopy examination for the cervix between January 2018 and January 2020 were divided into three groups according to the level of cervical intraepithelial neoplasia (CIN): Low-level group (Group A, n = 101), high-level group (Group B, n = 149), cervical cancer group (Group C, n = 50) and gynecological inflammation group (Group D, n = 60). Tissue samples were collected from subjects above to perform the immunohistochemistry for E6/E7 protein and detection of HPV DNA and HPV E6/E7 mRNA. The results showed that HPV DNA copies and the positive rates of protein, DNA and mRNA of HPV E6/E7 in Groups A, B and C were significantly higher than those in Group D (all P<0.05), while no significant difference was identified in the comparison of the positive rate and copies of DNA among Group A, B and C (P> 0.05); in the Group A, B and C, patients had a higher positive rate of E6/E7 mRNA than those in the Group D (P<0.05), while in the Group B and C, the positive rate and copies of mRNA of HPV E6/E7 and HPV E6/E7 proteins were all higher than those in the Group A (P<0.05). In addition, the specificity of HPV E6/E7 mRNA was inferior to HPV DNA in the detection of the low-level intraepithelial neoplasia, but it performed better in the detection of the high-level intraepithelial neoplasia and cervical cancer. In general, HPV E6/E7 mRNA shows promising value in the detection of the development and progression of cervical cancer.

Cervical cancer is the most common gynecological malignancy and screening for risk factors with early detection has been shown to reduce the mortality. In this study, we aimed to analyze the characteristics and risk factors of human papillomavirus (HPV) infection and precancerous lesions in women and provide clinical evidence for developing strategies to prevent cervical precancerous lesions and cancer in women. Furthermore, we evaluated the influencing factors for high-risk HPV infection. From April 2018 to December 2021, 10,628 women were recruited for cervical cancer screening at Liaoning Cancer Hospital, Shenyang Sujiatun District Women’s and Infants Hospital, Benxi Manchu Autonomous County People’s Hospital, and Shandong Affiliated Hospital of Qingdao University. The study participants were tested to determine if they were HPV-positive (HPV +) or underwent thinprep cytology test (TCT) for atypical squamous cells of undetermined significance (ASCUS) and above. Furthermore, colposcopies and biopsies were performed for the histopathological examination. Finally, 9991 cases were included in the statistical analysis, and the factors influencing HPV infection and those related to cervical cancer and precancerous lesions were analyzed. HPV + infection, high-grade squamous intraepithelial lesion-positive (CINII +) in cervical high-grade intraepithelial neoplasia, and early cervical cancer diagnosis rates were 12.45, 1.09, and 95.41%, respectively. The potential risk factors for HPV were education ≤ high school [odds ratio (OR) = 1.279 (1.129–1.449), P < 0.001], age at initial sexual activity ≤ 19 years [OR = 1.517 (1.080–2.129), P = 0.016], sexual partners > 1 [OR = 1.310 (1.044–1.644), P = 0.020], ASCUS and above [OR = 11.891 (10.105–13.993), P < 0.001], non-condom contraception [OR = 1.255 (1.059–1.487), P = 0.009], and HSIL and above [OR = 1.541 (1.430–1.662), P < 0.001]. Compared with women aged 56–65 and 35–45 years [OR = 0.810 (0.690–0.950), P = 0.010] the HPV infection rate was significantly lower in those aged 46–55 years [OR = 0.79 (0.683–0.915), P = 0.002]. Furthermore, ≤ high school age [OR = 1.577 (1.042–2.387), P = 0.031], not breastfeeding [OR = 1.763 (1.109–2.804), P = 0.017], ASCUS and above [OR = 42.396 (28.042–64.098), P < 0.001] were potential risk factors for cervical cancer and precancerous lesions. In women with HPV infection, ≤ high school education level, initial sexual activity at ≤ 19 years of age, number of sexual partners > 1, ASCUS and above, non-condom contraception, HSIL and above were risk factors for HPV infection. Compared with women aged 56–65 years, those aged 35–45 and 46–55 years had significantly lower HPV infection rates, and high school age and below, non-breastfeeding, and ASCUS and above were all potential risk factors for cervical cancer and precancerous lesions.

Background: To investigate the survival outcomes of abdominal radical hysterectomy (ARH), laparoscopic radical hysterectomy (LRH), and vaginal-assisted laparoscopic radical hysterectomy (VALRH) in the treatment of cervical cancer patients. Methods: This was a retrospective study. We collected the clinical data of 654 patients with cervical cancer (406 ARH, 172 LRH, and 76 VALRH), then compared the effects of different surgical methods on recurrence and survival. Results: Total overall survival (OS) were no significant differences in three groups (P>0.05). Total disease-free survival (DFS) was significantly higher in ARH group than in LRH group [hazard ratio (HR) =2.8, 95% confidence interval (CI): 1.199-3.607, P=0.004]; however, there were no significant differences between the VALRH (94.7%) and ARH (93.3%) groups. Subgroup stratification analysis showed that the overall recurrence rate in LRH group was significantly higher than that of the ARH groups for patients with a tumor size from >= 2 to <4 cm, negative postoperative lymph nodes, and no postoperative adjuvant therapy (all P<0.05). However, in the subgroup with tumor sizes of >= 2, <4, and >= 4 cm, no matter whether the lymph nodes were positive or not, and those with no postoperative supplementary adjuvant therapy, LRH was associated with a significantly higher local pelvic recurrence rate than ARH (all P<0.05). No significant differences between VALRH and ARH in any of the subgroup analyses (all P>0.05). A Cox analysis indicated that LRH increased the risk of overall and local pelvic recurrence after surgery compared with ARH (HR =2.338, 95% CI: 1.186-4.661, P=0.014; HR =10.313, 95% CI: 2.839-37.460, P<0.001); however, no significant difference between VALRH and ARH (all P>0.05). Sensitivity analysis of surgeons did not change the conclusions. Conclusions: Our analyses showed that the local pelvic recurrence rates and overall recurrence rates of LRH were significantly higher than ARH. VALRH could avoid tumor intraperitoneal exposure and achieve the same tumor prognosis as open surgery. By improving the standardization of minimally invasive surgery for early cervical cancer and paying close attention to the tumor-free concept, minimally invasive radical hysterectomy may achieve the same tumor outcome as open surgery.

BACKGROUND:Anaplastic carcinoma mural nodules in ovarian mucinous tumors are very rare. This study aimed to report the morphological characteristics, molecular detection results, clinical treatment and prognosis of three ovarian mucinous tumors with mural nodules of anaplastic carcinoma.CASE SUMMARY:The pathomorphological features, molecular detection results, clinical treatment and prognosis of anaplastic carcinoma mural nodules were described in three cases. In case 1, sarcoma-like mural nodules (SLMNs) coexisted with anaplastic carcinoma mural nodules. No mutation was found in mucinous tumors. KRAS mutation was found in anaplastic carcinoma nodules and heterotypic cells were found in SLMNs. In case 2, KRAS mutation occurred in the mucinous epithelium and BRAF mutation occurred in mural nodules. In case 3, both mural nodules and mucinous tumors had the same KRAS mutation and a morphological transition between them was observed. All three patients died within 2 years, whether receiving chemotherapy or not.CONCLUSION:Anaplastic carcinoma mural nodules may develop from dedifferentiation of mucinous tumors or are unrelated to mucinous tumors.

The different human papillomavirus (HPV) strains cause warts in various regions of the body. However, considering that the status and genotype distribution of HPV infection in women in Shenyang remain unknown, herein, we investigated the epidemiological characteristics of high-risk HPV (HR-HPV) infection in women in Shenyang, as well as the current state of HPV infection in Shenyang, to provide a theoretical basis for the prevention and treatment of cervical cancer. From December 2018 to December 2021, 6,432 urban and rural women from the Liaoning Cancer Hospital and the Sujiatun Women and Infants’ Hospital were assessed via the Thinprep cytology test (TCT) and HR-HPV detection. Of the 5,961 women enrolled, 739 were HPV positive (12.40%) and 562 were TCT positive (9.43%). Statistical analyses identified the following HPV risk factors: high school education or lower [OR = 1.426 (1.199–1.696), p < 0.001], age at first sexual encounter ≤ 19 years [OR = 1.496 (1.008–2.220), p = 0.046], and number of sexual partners > 1 [OR = 1.382 (1.081–1.768), p = 0.010], atypical squamous cells of undetermined significance (ASCUS) and above [OR = 10.788 (8.912–13.060), p < 0.001], non-condom-based contraception [OR = 1.437 (1.103–1.871), p = 0.007], nationalities other than Han [OR = 1.690 (1.187–2.406), p = 0.004], rural residence [OR = 1.210 (1.031–1.419), p = 0.020]. Compared to the HPV infection rate of women aged 56–65, that in women aged 35–45 [OR = 0.687 (0.549–0.860), p = 0.001] and 46–55 [OR = 0.740 (0.622–0.879), p = 0.001] decreased significantly. To conclude, risk factors of HPV infection among female patients include high school age and below, initial sexual encounter at age ≤ 19 years, number of sexual partners > 1, ASCUS and above, non-condom contraception, nationalities other than Han nationality and rural population. Collectively, this study provides insights for the improved prevention and treatment of cervical cancer.

In this prospective study of an in-vivo cervical examination using optical coherence tomography (OCT), we evaluated the diagnostic value of non-invasive and real-time OCT in cervical precancerous lesions and cancer diagnosis, and determined the characteristics of OCT images. 733 patients from 5 Chinese hospitals were inspected with OCT and colposcopy-directed biopsy. The OCT images were compared with the histological sections to find out the characteristics of various categories of lesions. The OCT images were also interpreted by 3 investigators to make a 2-class classification, and the results were compared against the pathological results. Various structures of the cervical tissue were clearly observed in OCT images, which matched well with the corresponding histological sections. The OCT diagnosis results delivered a sensitivity of 87.0% (95% confidence interval, CI 82.2-90.7%), a specificity of 84.1% (95% CI 80.3-87.2%), and an overall accuracy of 85.1%. Both good consistency of OCT images and histological images and satisfactory diagnosis results were provided by OCT. Due to its features of non-invasion, real-time, and accuracy, OCT is valuable for the in-vivo evaluation of cervical lesions and has the potential to be one of the routine cervical diagnosis methods.

This paper was designed to explore the value of miRNAs as diagnostic biomarkers that may facilitate the early detection of esophageal squamous cell carcinoma (ESCC). Plasma miRNA profiles were defined via an array-based approach using samples from ESCC patients and healthy controls (n=5 each). Differentially expressed miRNAs in these samples were validated via qPCR in ESCC patients (n=96) and healthy controls (n=51), and the relationship between ESCC patient plasma miR-1260b and miR-720 levels and clinicopathological characteristics were additionally examined. In total, 12 plasma miRNAs that were differentially expressed between ESCC patients and healthy controls were identified via miRNA. Six of these miRNAs were subsequently validated, revealing that both miR-1260b and miR-720 were significantly differentially abundant in ESCC patients and controls, with miR-1260b being significantly upregulated in ESCC patients relative to controls (2.24, 1.41 respectively, P<0.001), while the opposite was observed with respect to miR-720 (0.66, 2.27 respectively, P=0.001). The use of both miR-720 and miR-1260b as a combined diagnostic tool was highly efficacious, yielding an AUC of 0.814, a sensitivity of 86.3%, and a specificity of 73.2% as a means of detecting ESCC patients. Elevated plasma miR-1260b level was also associated with a poorer patient prognosis when compared to patients with a low plasma miRNA level (P=0.021). This study has successfully developed a plasma miRNA biomarker signature of ESCC that may offer value as a diagnostic or prognostic tool when evaluating patients with ESCC.

Background:Anaplastic carcinoma mural nodules presenting in ovarian mucinous cystic tumors are very rare. Here, we reported clinicopathological, immunohistochemical and molecular features of 3 such cases, and reviewed the related literature.Case presentation:The expression of pan-cytokeratin (CK) in the mural nodules of all three patients supported the diagnosis of mural nodules of anaplastic carcinoma. Immunohistochemical staining showed wild-type expression of p53 in the mural nodules and mucinous epithelium of Cases 2 and 3, while Case 1 was negative for the p53 mutation. The synchronous expression of p53 in epithelia and mural nodules suggested that mural nodules might be homologous with mucinous adenocarcinoma and might be the result of dedifferentiation of mucinous adenocarcinoma. In the sarcomatoid region of Case 1, p53 was wild-type in spindle cells and multinucleated giant cells in the background. In Case 3, a broad-based serrated adenoma of the appendix was also found. Therefore, exons of tumor-related genes were detected by high-throughput next-generation sequencing (NGS). Missense mutations of PIK3CA and PTEN were found, but no germline mutations were detected.Conclusions:In young patients with sarcomalike mural nodule (SLMNs) morphology, pathological analysis is recommended to avoid overlooking the existence of malignant mural nodules. Serrated lesions occurred in the appendix and ovarian mucinous tumor simultaneously, but no germline mutations were detected by NGS, indicating this was a sporadic case.

Background Human papillomavirus (HPV), the most common sexually transmitted disease, is involved in a series of other diseases. The persistent infection of high-risk HPVs (HR-HPVs) is considered to be the causative agent of cervical cancer, and it is related to noncervical cancers. The present study aims to estimate the HPV prevalence and genotype distribution in Jilin province, China, to guide HPV-related cervical cancer screening and HPV vaccination. Methods From October 2017 to September 2019, 21,282 samples (634 male and 20,648 female) were collected for HPV infection detection using an HPV genotyping panel. The age-related HPV prevalence and morbidity of HPV-based disease and HPV prevalence associated with specific diseases were analyzed. Results A total of 7095 (34.4%) positive for HPV infection of 20648 women, and 164 (25.8%) positive of 634 men. The HPV prevalence among women exhibited a bimodal pattern, with a peak in young group and a second peak in old group, with increased severity of cervical lesions. HPV16 (7.8%), HPV52 (5.8%), HPV58 (5.0%), HPV53 (3.4%), and HPV51 (3.0%) were the most prevalent genotypes among women, and HPV6 (6.0%), HPV11 (5.7%), HPV16 (3.6%), HPV18 (2.7%), and HPV51 (3.0%) were prevalent among men. Non-vaccine-covered HPV53 and 51 were found in 6.3% of HPV infection and 8.9% of cervical cancer in Jilin province. Furthermore, 45.5% of females and 28.6% of males with genital warts were infected with HR-HPV genotypes. Conclusion The HPV genotypic spectrum in Jilin province, where non-vaccine-covered HPV53 and 51 were prevalent, exhibited an age- and cervical lesion-specific pattern, which provides guidance for HPV vaccination and cervical cancer screening. HPV infection in men and benign hyper-proliferative lesions should not be neglected.

Gene expression microarray and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of miR-126. In model of diabetic nephropathy, we demonstrated that miR-126 expression was down-regulated, compared with control group. Down-expression of miR-126 promoted cell apoptosis and increased inflammation (as indicated by the levels of IL-1 beta, IL-6, IL-18 and TNF-alpha) of diabetic nephropathyin vitro. miR-126 over-expression led to significant inhibition of cell apoptosis and suppressed inflammation (IL-1 beta, IL-6, IL-18 and TNF-alpha). However, the down-expression of miR-126 suppressed the protein expression of VEGF, PI3K and p-AKT in diabetic nephropathyin vitro. On the contrary, over-expression of miR-126 induced the protein expression of VEGF, PI3K and p-AKT in diabetic nephropathyin vitro. The inhibition of VEGF increased the effect of miR-126 down-expression on apoptosis and inflammation in diabetic nephropathyin vitro. We investigated the specific function of miR-126 in patients with diabetic nephropathy and its possible mechanism.

BACKGROUND Early detection of nonalcoholic fatty liver disease (NAFLD) shows its significant efficacy in preventing the patients from liver failure. The ultrasonic image quantitative analysis software can assist to diagnose NAFLD in the clinical studies. In this study, we aim to explore new method to evaluate the value of computer-assisted ultrasound in diagnosis and classification of fatty liver via Image J software. METHODS Forty Sprague-Dawley rats were randomly divided into control group (n=10) and model group (n=30). For model group, the rats received high fat diet and subcutaneous injection of carbon tetrachloride to establish nonalcoholic fatty liver model. Ultrasound and pathological examinations on rats were performed on 4, 8, and 12 weeks. Image J software was used to measure the liver grayscale value (LGV) and renal grayscale value (RGV). The difference between LGV and RGV (LRGV) was analyzed. The diagnostic performance of computer-assisted ultrasound quantification was evaluated by receiver operating characteristic (ROC) analysis. RESULTS We compared ultrasonic quantization parameters between control and model groups and found that the LGV and LRGV were statistically different between the normal and light fatty livers, light and moderate fatty livers, as well as moderate and severe fatty livers, respectively (P<0.05). There was no significant difference in RGV among these groups (P>0.05). Kappa statistic and Bland-Altman analyses showed the consistency of ultrasonic examination and pathological examination was good in diagnosis of fatty liver. CONCLUSIONS This study indicated that the computer-assisted ultrasound quantification analysis, with high performance of NAFLD diagnosis like pathological examination, could provide a new and flexible noninvasive method for preclinical pharmacological research and basic research.

Trigonelline has been reported to serve an important role in cell cycle control, oxidative and ultraviolet stress and DNA methylation. In the present study, the effects of trigonelline were examined on type-2 diabetes mellitus (T2DM)-induced renal dysfunction, and its possible mechanism was investigated. Sprague-Dawley rats were fed with high-fat diet (HFD) for 4 weeks and intraperitoneally injected with 35 mg/kg of streptozotocin for 4 weeks. As a result, trigonelline increased body weight, inhibited the kidney weight/body weight ratio and blood glucose levels, and reduced the levels of blood urea nitrogen, creatinine and albumin in type 2 diabetic rats. In addition, trigonelline also reduced inflammation, oxidative stress and kidney cell apoptosis in T2DM rats. In terms of the molecular mechanisms involved, trigonelline induced the protein expression of peroxisome proliferator-activated receptor (PPAR)-γ and suppressed glucose transporter 4 but suppressed the protein expression of tumor necrosis factor-α and leptin in T2DM rats. The present results demonstrated that trigonelline reduced diabetic nephropathy and insulin resistance in T2DM rats through PPAR-γ.

Objective: To evaluate the diagnostic performance of ultrasonic elastography combined with contrast enhanced ultrasonography in quantitative or semi-quantitative assessment of liver fibrosis. Methods: Rat Liver fibrosis model was established. According to the degree of liver fibrosis they were divided into three groups, S1 (11 cases), S2 (9 cases), S3 (7 cases) and a control group (10 cases) was established. Ultrasound elastography, contrast enhanced ultrasonography and two techniques combined method were used respectively for the diagnosis of the liver fibrosis. The diagnosis was compared with the pathological diagnosis to evaluate their clinical value. Results: HVAT and HA-HVTT were decreased with the severity of liver fibrosis (P<0.05). Semi-quantitative fibrosis scores and the relative content of collagen increased gradually with the severity of liver fibrosis. There was a significant negative correlation between HA-HVTT and semi-quantitative fibrosis scores or relative content of collagen (r1=-0.828, r(2)=-0.819) respectively. The sensitivity and specificity of the liver fibrosis diagnosis (S3) in contrast enhanced ultrasonography were 85.71% and 66.67% respectively, while they were 71.43% and 53.33% by ultrasound elastography respectively. However, the sensitivity and specificity were increased at 85.71% and 73.33% by ultrasound elastography combined with contrast enhanced ultrasonography respectively. Conclusion: Quantitative ultrasound parameters can be used as an indicator of noninvasive liver fibrosis diagnosis. Contrast enhanced ultrasonography combined with ultrasonic elastography improved the specificity and reduced the misdiagnosis rate.