The value of microvascular Doppler ultrasound technique, qualitative or quantitative shear-wave elastography of breast lesions for predicting axillary nodal burden in patients with breast cancer.

Background: The status of the axillary lymph node (ALN) in patients with breast cancer can critically inform clinical decision-making and prognosis. Preoperative evaluation of limited nodal burden (0-2 metastatic ALNs) and high nodal burden (≥3 metastatic ALNs) is vital for individual treatment in patients with breast cancer. Thus, this study aimed to evaluate the value of Angio-PLUS (AP; Aixplorer, SuperSonic Imagine) and the qualitative and quantitative shear-wave elastography (SWE) of breast lesions to predict limited or high axillary nodal burden and to develop a model for predicting limited or high axillary nodal burden. Methods: From March 2020 to November 2022, a total of 232 consecutive patients with breast cancer comprising 232 breast lesions were enrolled retrospectively from Yueyang Central Hospital. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy, and area under the receiver operating characteristic curve (AUC) of AP, qualitative SWE, quantitative SWE, and the predictive model for evaluating limited or high axillary nodal burden were compared. Results: There was no significant difference in AP patterns between the limited nodal burden group and high nodal burden group. The best cutoff values of Emin (the minimal value of the first Q-box), Emean (the mean value of the first Q-box), Emax (the maximum value of the first Q-box), Eratio (ratio of the first Q-Box and the second Q-Box) and standard deviation for predicting limited or high nodal burden were 80.85 KPa, 133.45 KPa, 153.40 KPa, 9.95, and 19.25 KPa, respectively. The Emax had the highest AUC, and its sensitivity, specificity, PPV, NPV, accuracy, and AUC were 71.64%, 56.36%, 40.00%, 83.04%, 60.78%, and 0.640 [95% confidence interval (CI): 0.575-0.702], respectively. The sensitivity, specificity, PPV, NPV, accuracy, and AUC of seven color patterns for qualitative SWE were 71.64%, 74.55%, 53.33%, 86.62%, 73.71%, and 0.731 (95% CI: 0.669-0.787), respectively, which was significantly higher than all the other quantitative SWE parameters. ALN evaluation in ultrasound and qualitative SWE were independent risk factors for predicting limited or high nodal burden according to a binary logistics regression analysis. The AUC of the predictive model based on independent risk factors was 0.820 (95% CI: 0.765-0.867), which was significantly higher than that of the other independent risk factors. Conclusions: The seven color patterns in the qualitative SWE of breast lesions were valuable for predicting limited or high nodal burden for patients with breast cancer. Compared with quantitative SWE, qualitative SWE exhibited a better diagnostic performance. Breast lesions present no findings, vertical stripes, and spot patterns were important indicators for limited nodal burden. The predictive model developed in this study could be a simple, noninvasive, and convenient method for predicting limited or high nodal burden, which would be beneficial for clinical decision-making and individual treatment to improve prognosis.

The value of quantitative and a new qualitative color pattern shear wave elastography for the differentiation of ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm.

Objective: This study aims to evaluate the diagnostic performance of quantitative shear wave elastography (SWE) and a new qualitative color pattern SWE for the differentiation of benign and malignant American College of Radiology Thyroid Imaging, Reporting, and Data System (ACR TI-RADS) 4 or 5 category thyroid nodules measuring ≤10 mm. Materials and methods: From May 2020 to July 2022, a total of 237 patients with 270 thyroid nodules were enrolled, and conventional ultrasound and SWE examinations were performed for each patient. Each ACR TI-RADS 4 or 5 category thyroid nodule measuring ≤10 mm was evaluated by quantitative SWE and a new qualitative color pattern SWE. The diagnostic performance of quantitative SWE parameters, the new qualitative color pattern SWE, and the combination of SWE with ACR TI-RADS, respectively, for the differentiation of benign and malignant ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm was evaluated and compared. Results: Among 270 thyroid nodules in 237 patients, 72 (26.67%) thyroid nodules were benign and 198 (73.33%) thyroid nodules were malignant. The qualitative color pattern SWE showed better diagnostic performance than the quantitative SWE parameters. When combining the qualitative color pattern SWE with ACR TI-RADS scores, with the optimal cutoff value of the total points ≥8, the thyroid nodules were considered malignant. The sensitivity, specificity, accuracy, and AUC were 89.90%, 56.94%, 81.11%, and 0.820 (95% CI: 0.768-0.864), respectively. Compared with using qualitative color pattern SWE alone, the combination of qualitative color pattern SWE and ACR TI-RADS had better diagnostic performance, which was significantly different (p < 0.05). Conclusion: The combination of qualitative SWE color patterns and ACR TI-RADS had high sensitivity and accuracy, which might be a convenient and useful method to differentiate benign and malignant ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm. It would be helpful for the management of thyroid nodules and improving prognosis.

A model based on clinical data and multi-modal ultrasound for predicting cervical lymph node metastasis in patients with thyroid papillary carcinoma.

Objective: The aim of this study was to explore diagnostic performance based on clinical characteristics, conventional ultrasound, Angio PLUS (AP), shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) for the preoperative evaluation of cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) and to find a reliable predictive model for evaluating CLNM. Materials and methods: A total of 206 thyroid nodules in 206 patients were included. AP, SWE, and CEUS were performed for all thyroid nodules. Univariate analysis and multivariate logistic regression analysis were performed to ascertain the independent risk factors. The sensitivity, specificity, and the area under the curve (AUC) of independent risk factors and the diagnostic model were compared. Results: Sex, age, nodule size, multifocality, contact extent with adjacent thyroid capsule, Emax, and capsule integrity at CEUS were independent risk predictors for CLNM in patients with PTC. A predictive model was established based on the following multivariate logistic regression: Logit (p) = -2.382 + 1.452 × Sex - 1.064 × Age + 1.338 × Size + 1.663 × multifocality + 1.606 × contact extent with adjacent thyroid capsule + 1.717 × Emax + 1.409 × capsule integrity at CEUS. The AUC of the predictive model was 0.887 (95% CI: 0.841-0.933), which was significantly higher than using independent risk predictors alone. Conclusion: Our study found that male presence, age < 45 years, size ≥ 10 mm, multifocality, contact extent with adjacent thyroid capsule > 25%, Emax ≥ 48.4, and interrupted capsule at CEUS were independent risk predictors for CLNM in patients with PTC. We developed a diagnostic model for predicting CLNM, which could be a potentially useful and accurate method for clinicians; it might be beneficial to surgical decision-making and patient management and for improving prognosis.

Combined Use of Shear Wave Elastography, Microvascular Doppler Ultrasound Technique, and BI-RADS for the Differentiation of Benign and Malignant Breast Masses.

Objective: To evaluate the value of the combined use of Breast Imaging Reporting and Data System (BI-RADS), qualitative shear wave elastography (SWE), and AngioPLUS microvascular Doppler ultrasound technique (AP) for distinguishing benign and malignant breast masses. Materials and Methods: A total of 210 pathologically confirmed breast lesions in 210 patients were reviewed using BI-RADS, qualitative SWE, and AP. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy, and area under the receiver operating characteristic curve (AUC) of BI-RADS and the combination of qualitative SWE and/or AP with BI-RADS were compared, respectively. Results: Compared with using BI-RADS alone, the use of combined qualitative SWE and/or AP with BI-RADS had higher AUC values (P < 0.001). Besides this, the combination of qualitative SWE and AP with BI-RADS had the best diagnostic performance for differentiating between benign and malignant masses. When AP and SWE were combined with BI-RADS, 49/76 benign masses were downgraded from BI-RADS category 4a into BI-RADS category 3, while no benign masses were upgraded from BI-RADS category 3 into BI-RADS category 4a. Three sub-centimeter malignant masses were downgraded from BI-RADS category 4a into BI-RADS category 3, while three malignant masses remain in BI-RADS category 3 due to a benign manifestation in both AP and qualitative SWE. Moreover, 5/6 of them were sub-centimeter masses, and 4/6 of them were intraductal carcinoma. The sensitivity, specificity, PPV, NPV, accuracy, and AUC were 91.0%, 81.1%, 69.3%, 95.1%, 84.3%, and 0.861 (95% confidence interval, 0.806-0.916; P < 0.001), respectively. Compared with BI-RADS alone, the sensitivity slightly decreased, while the specificity, PPV, NPV, and accuracy were significantly improved. Conclusion: Combination of qualitative SWE and AP with BI-RADS improved the diagnostic performance in differentiating benign from malignant breast lesions, which is helpful for avoiding unnecessary biopsies. However, we should be careful about the downgrading of sub-centimeter BI-RADS 4a category lesions.

Membrane-cloaked polydopamine modified mesoporous silica nanoparticles for cancer therapy.

To improve the shortcomings of narrow therapeutic range and low bioavailability of traditional preparations, a composite drug carrier that combines the advantages of biological carriers and synthetic carriers was prepared in this project. The biomimetic nano-delivery system outer membrane vesicles-polydopamine-mesoporous silica nanoparticle (OMVs-PDA-MSN-DOX) for oral administration is composed of OMVs ofEscherichia colias shell and doxorubicin-loaded MSN modified by PDA as core. Several characterization techniques thoroughly examined the nano-drug delivery system to confirm its surface morphology and chemical property. OMVs-PDA-MSN-DOX with a particle size of 150 nm showed significant cell selectivity and safety. We demonstrated that OMVs are capable of protecting pH-sensitive nanostructure from the oral route of administration in the short term. Importantly, OMVs-PDA-MSN-DOX could facilitate intestinal adhesion and improve DOX bioavailability. Overall, the OMVs-cloaked nanocarrier provides an efficient delivery platform for the oral targeting treatment of cancer with pH-sensitive nano-formulations.

Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury.

OBJECITVIE: To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen (APAP)-induced hepatotoxicity. METHODS: Totally 90 Kunming mice were randomly divided into 10 groups according to body weight (9 mice for each group). The mice in the normal control and model (vehicle control) groups were administered sodium carboxymethyl cellulose (CMC-Na, 0.5%) only. Administration groups were pretreated with high and low-dose dry dandelion extract (1,000 or 500 g fresh herb dried and then decocted into 120 mL solution, DDE-H and DDE-L); low-, medium- and high-dose dandelion juice (250, 500, 1,000 g/120 mL, DJ-L, DJ-M, and DJ-H); fresh dandelions evaporation juice water (120 mL, DEJW); dry dandelion extract dissolved by pure water (1 kg/120 mL, DDED-PW); dry dandelion extract dissolved by DEJW (120 g/120 mL, DDED-DEJW) by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight; after that, except normal control group, all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver injury. Twenty hours after APAP administration, serum and liver tissue were collected and serum alanine aminotransferase (AST), aspartate transaminase (ALT), alkaline phosphatase (AKP), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) activities were quantified by biochemical kits; tumor necrosis factor (TNF-α), interleukin (IL)-2, and IL-1 ß contents in liver tissue were determined by enzyme linked immunosorbent assay kits. Histopathological changes in liver tissues were observed by hematoxylin and eosin staining; TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis evaluation. The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid-2-related factor 2 (Nrf-2), caspase-9, B-cell leukemia/lymphoma 2 (Bcl-2), Bax and p-JNK were determined by Western blot analysis. RESULTS: Pretreatment with fresh dandelion juice (FDJ, including DJ-L, DJ-M, DJ-H, DEJW and DDED-DEJW) significantly decreased the levels of serum ALT, AST, AKP, TNF-α and IL-1ß compared with vehicle control group (P<0.05 or P<0.01). Additionally, compared with the vehicle control group, FDJ decreased the levels of hepatic MDA and restored GSH levels and SOD activity in livers (P<0.05 or P<0.01). FDJ inhibited the overexpression of pro-inflammatory factors including cyclooxygenase-2 and inducible nitric oxide synthase in the liver tissues (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that FDJ pretreatment inhibited activation of apoptotic signaling pathways via decreasing of Bax, and caspase-9 and JNK protein expression, and inhibited activation of JNK pathway (P<0.05 or P<0.01). Liver histopathological observation provided further evidence that FDJ pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration and congestion. CONCLUSIONS: FDJ pretreatment protects against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway, and the effect of fresh dandelion extracts was superior to dried dandelion extracts in APAP hepatotoxicity model mice.

Contrast-enhanced ultrasound and shear wave elastography in the diagnosis of ACR TI-RADS 4 and 5 category thyroid nodules coexisting with Hashimoto's thyroiditis.

Objective: This study aims to evaluate the value of contrast-enhanced ultrasound (CEUS), shear wave elastography (SWE), and their combined use in the differentiation of American College of Radiology (ACR) thyroid imaging reporting and data system (TI-RADS) 4 and 5 category thyroid nodules coexisting with Hashimoto's thyroiditis (HT). Materials and methods: A total of 133 pathologically confirmed ACR TI-RADS 4 and 5 category nodules coexisting with HT in 113 patients were included; CEUS and SWE were performed for all nodules. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy, and the area under the receiver operating characteristic curve (AUC) of the SWE, CEUS, and the combined use of both for the differentiation of benign and malignant nodules were compared, respectively. Results: Using CEUS alone, the sensitivity, specificity, PPV, NPV, and accuracy were 89.2%, 66.0%, 81.3%, 78.6%, and 80.5%, respectively. Using SWE alone, Emax was superior to Emin, Emean, and Eratio for the differentiation of benign and malignant nodules with the best cutoff Emax >46.8 kPa, which had sensitivity of 65.1%, specificity of 90.0%, PPV of 91.5%, NPV of 60.8%, and accuracy of 74.4%, respectively. Compared with the diagnostic performance of qualitative CEUS or/and quantitative SWE, the combination of CEUS and SWE had the best sensitivity, accuracy, and AUC; the sensitivity, specificity, PPV, NPV, accuracy, and AUC were 94.0%, 66.0%, 82.1%, 86.8%, 83.5%, and 0.80 (95% confidence interval: 0.713, 0.886), respectively. Conclusion: In conclusion, CEUS and SWE were useful for the differentiation of benign and malignant ACR TI-RADS 4 and 5 category thyroid nodules coexisting with HT. The combination of CEUS and SWE could improve the sensitivity and accuracy compared with using CEUS or SWE alone. It could be a non-invasive, reliable, and useful method to differentiate benign from malignant ACR TI-RADS 4 and 5 category thyroid nodules coexisting with HT.

Machine learning-assisted ensemble analysis for the prediction of urinary tract infection in elderly patients with ovarian cancer after cytoreductive surgery.

BACKGROUND: Urinary tract infection (UTI) is a common type of postoperative infection following cytoreductive surgery for ovarian cancer, which severely impacts the prognosis and quality of life of patients. AIM: To develop a machine learning assistant model for the prevention and control of nosocomial infection. METHODS: A total of 674 elderly patients with ovarian cancer who were treated at the Department of Gynaecology at Jingzhou Central Hospital between January 31, 2016 and January 31, 2022 and met the inclusion criteria of the study were selected as the research subjects. A retrospective analysis of the postoperative UTI and related factors was performed by reviewing the medical records. Five machine learning-assisted models were developed using two-step estimation methods from the candidate predictive variables. The robustness and clinical applicability of each model were assessed using the receiver operating characteristic curve, decision curve analysis and clinical impact curve. RESULTS: A total of 12 candidate variables were eventually included in the UTI prediction model. Models constructed using the random forest classifier, support vector machine, extreme gradient boosting, and artificial neural network and decision tree had areas under the receiver operating characteristic curve ranging from 0.776 to 0.925. The random forest classifier model, which incorporated factors such as age, body mass index, catheter, catheter intubation times, blood loss, diabetes and hypoproteinaemia, had the highest predictive accuracy. CONCLUSION: These findings demonstrate that the machine learning-based prediction model developed using the random forest classifier can be used to identify elderly patients with ovarian cancer who may have postoperative UTI. This can help with treatment decisions and enhance clinical outcomes.

[Preparation of nanoemulsion spray from Moslae Herba volatile oil and its antibacterial activity].

Moslae Herba is a commonly used aromatic Chinese medicinal with volatile oil as the main effective component and exhibits broad-spectrum antibacterial and antiviral effects. However, the irritation and instability of Moslae Herba volatile oil necessitate the preparation into a specific dosage form. In this study, the steam distillation method was employed to extract the Moslae Herba volatile oil. The content of thymol and carvacrol in Moslae Herba volatile oil was determined by HPLC as(0.111 9±0.001 0) and(0.235 4±0.004 7) mg·mL~(-1), respectively. Pseudo-ternary phase diagrams and surfactants compounding were applied in the selection of the optimal excipients(surfactant and cosurfactant). On this basis, a nanoemulsion was prepared from the Moslae Herba volatile oil and then loaded into pressure vessels to get sprays, whose stability and antibacterial activity were evaluated afterward. With clarity, viscosity, smell and body feeling as comprehensive indexes, the optimal formulation of the Moslae Herba volatile oil nanoemulsion was determined as follows: Moslae Herba volatile oil∶peppermint oil∶cremophor EL∶absolute ethanol∶distilled water 7.78∶1.58∶19.26∶6.15∶65.23. The as-prepared nanoemulsion was a light yellow transparent liquid, with Tyndall effect shown under the irradiation of parallel light. It has the pH of 5.50, conductivity of 125.9 µS·cm~(-1), average particle size of 15.45 nm, polydispersity index(PDI) of 0.156, and Zeta potential of-17.9 mV. Under a transmission electron microscope, the Moslae Herba volatile oil nanoemulsion was presented as regular spheres without adhesion and agglomeration. Stability test revealed that the Moslae Herba volatile oil nanoemulsion was stable at 4-55 ℃, which was free from demulsification and stratification within 30 days. After the centrifugation at 12 000 r·min~(-1) for 30 min, there was no stratification either. The nanoemulsion had good inhibitory effects on Escherichia coli, Staphylococcus aureus and resistant S. aureus strains, with the minimum inhibitory concentrations of 0.39, 3.12 and 1.56 mg·mL~(-1), respectively. The above results demonstrated that the nanoemulsion was prepared feasibly and showed stable physical and chemical properties and good antibacterial effects. This study provides a practicable technical solution for the development of anti-epidemic and anti-infection products from Moslae Herba volatile oil.

Ultrasound Elastography for the Evaluation of Lymph Nodes.

The differential diagnosis of lymphadenopathy is important for predicting prognosis, staging, and monitoring the treatment, especially for cancer patients. Conventional computed tomography and magnetic resonance imaging characterize lymph node (LN) with disappointing sensitivity and specificity. Conventional ultrasound with the advantage of high resolution has been widely used for the LN evaluation. Ultrasound elastography (UE) using color map or shear wave velocity can non-invasively demonstrate the stiffness and homogeneity of both the cortex and medulla of LNs and can detect early circumscribed malignant infiltration. There is a need of a review to comprehensively discuss the current knowledge of the applications of various UE techniques in the evaluation of LNs. In this review, we discussed the principles of strain elastography and shear wave-based elastography, and their advantages and limitations in the evaluation of LNs. In addition, we comprehensively introduced the applications of various UE techniques in the differential diagnosis of reactive LNs, lymphoma, metastatic LNs, and other lymphadenopathy. Moreover, the applications of endoscopic UE and endobronchial UE are also discussed, including their use for improving the positive rate of diagnosis of fine-needle aspiration biopsy.

Adropin Alleviates Myocardial Fibrosis in Diabetic Cardiomyopathy Rats: A Preliminary Study.

Aim: Adropin (ADR) is a novel regulatory polypeptide and has important effects on energy metabolism in the heart. However, it is still unclear whether ADR can relieve ventricular remodeling in DCM. Therefore, this study was conducted to assess the effect of ADR on myocardial fibrosis in DCM rats. Materials and Methods: Twenty Wistar rats were randomly assigned into four groups: healthy control group (CON), DCM model group (DCM), DCM model treated with ADR group (ADR) and DCM model treated with perindopril group (PER). Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were calculated. Diastolic function was assessed by echocardiography. The mitochondrial membrane potential assay was conducted by Rhodamine 123 staining. The protein expression levels of Col I, Col III, Mitofusin-1, Mitofusin-2 and Drp1 were evaluated using western blot. Results: Compared to CON group, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 increased in DCM group. And the relative expression of Mitofusin-1 and Mitofusin-2 proteins decreased. During our investigations, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 decreased in ADR treated rats compared to DCM group. The diastolic function was elevated in ADR group. The fluorescence of Rhodamine 123 and the expression of Mitofusin-1 and Mitofusin-2 also increased in ADR group. Conclusion: Our study demonstrated that ADR could alleviate myocardial fibrosis and improve diastolic function in DCM rats. ADR may be a putative candidate for the treatment of DCM.

Elevated CA125 levels are associated with adverse clinical outcomes in acute pancreatitis: A propensity score-matched study.

OBJECTIVES: Glycosylation alterations are indicative of tissue inflammation and neoplasia. However, there are no large-sample, real-world studies assessing the levels of serum carbohydrate antigen 125 (CA125) in patients with acute pancreatitis (AP). We aimed to identify the association between elevated CA125 levels and adverse clinical outcomes in AP. METHODS: This was a retrospective cohort study with an analysis of 3939 patients with AP who were admitted to the First Affiliated Hospital of Nanchang University between January 2015 and September 2019 that used data from a prospectively maintained database. Multivariate logistic regression analysis and a propensity score-matched analysis were conducted to reveal the relationship between elevated CA125 levels and poor prognosis. RESULTS: The overall prevalence of elevated CA125 (>35 U/mL) levels was 38.51% (1517/3939) in AP patients. Elevated CA125 levels were independently associated with higher risks of mortality (adjusted odds ratio (AdjOR), 1.82; 95% confidence interval (CI), 1.30-2.54; P < 0.001), severe acute pancreatitis (SAP) (AdjOR, 2.40; 95% CI, 2.00-2.88; P < 0.001), and infected pancreatic necrosis (IPN) (AdjOR, 3.54; 95% CI, 2.65-4.71; P < 0.001). The propensity score-matched cohort analysis also demonstrated that mortality (OR, 1.57; 95% CI, 1.06-2.23; P < 0.05), SAP (OR, 2.20; 95% CI, 1.77-2.73; P < 0.001), and IPN (OR, 2.79; 95% CI, 1.98-3.92; P < 0.001) were more common in the elevated CA125 group than in the normal CA125 group. CONCLUSIONS: Elevated CA125 levels (>35 U/mL) are independently associated with adverse clinical outcomes in AP patients. These observations justify ongoing efforts to understand the role of CA125 in the pathogenesis and prognosis of AP.

Dural sac cross-sectional area is a highly effective parameter for spinal anesthesia in geriatric patients undergoing transurethral resection of the prostate: a prospective, double blinded, randomized study.

BACKGROUND: Spinal anesthesia is optimal choice for transurethral resection of the prostate (TURP), but the sensory block should not cross the T10 level. With advancing age, the sensory blockade level increases after spinal injection in some patients with spinal canal stenosis. We optimize the dose of spinal anesthesia according to the decreased ratio of the dural sac cross-sectional area (DSCSA), the purpose of this study is to hypothesis that if DSCSA is an effective parameter to modify the dosage of spinal anesthetics to achieve a T10 blockade in geriatric patients undergoing TURP. METHODS: Sixty geriatric patients schedule for TURP surgery were enrolled in this study. All subjects were randomized divided into two groups, the ultrasound (group U) and the control (group C) groups, patient receive either a dose of 2 ml of 0.5% isobaric bupivacaine in group C, or a modified dose of 0.5% isobaric bupivacaine in group U. We measured the sagittal anteroposterior diameter (D) of the dural sac at the L3-4 level with ultrasound, and calculated the approximate DSCSA (A) according to the following formula: A = π(D/2)2, ( π = 3.14). The modified dosage of bupivacaine was adjusted according to the decreased ratio of the DSCSA. RESULTS: The cephalad spread of the sensory blockade level was significantly lower (P < 0.001) in group U (T10, range T7-T12) compared with group C (T3, range T2-T9). The dosage of bupivacaine was significantly decreased in group U compared with group C (P < 0.001). The regression times of the two segments were delay in group U compared with group C (P < 0.001). The maximal decrease in MAP was significantly higher in the group C than in group U after spinal injection (P < 0.001), without any modifications HR in either group. Eight patients in group C and two patients in group U required ephedrine (P = 0.038). CONCLUSIONS: The DSCSA is a highly effective parameter for spinal anesthesia in geriatric patients undergoing TURP, a modified dose of local anesthetic is a critical factor for controlling the sensory level. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800015566).on 8, April, 2018.

Comparison of Contrast-Enhanced Ultrasound versus Contrast-Enhanced Magnetic Resonance Imaging for the Diagnosis of Focal Liver Lesions Using the Liver Imaging Reporting and Data System.

The aim of this retrospective study was to evaluate the Liver Imaging Reporting and Data System (LI-RADS) categorization of focal liver lesions (FLLs) on contrast-enhanced ultrasound (CEUS) in comparison with contrast-enhanced magnetic resonance imaging (CE-MRI). A total of 63 patients with 84 FLLs were included in the final study population, after review of the electronic medical records and clinical data. Two trained radiologists evaluated all CEUS and CE-MRI images independently. They assigned a LI-RADS category to each FLL and assessed major features based on CEUS LI-RADS Version 2017 and computed tomography/MRI LI-RADS Version 2018. The generalized estimating equation method was used to compare the diagnostic performance of the LI-RADS algorithm between CEUS and CE-MRI. The sensitivity of LR-5/LR-TIV (tumor in vein) categories for diagnosing hepatocellular carcinoma (HCC) differed significantly between CEUS and CE-MRI (88.9% [40/45], 95% confidence interval [CI]: 76.5%-95.2%), versus 64.4% (29/45; 95% CI: 49.8%-76.8%), p = 0.006; 82.2% (37/45; 95% CI: 68.7%-90.7%), versus 62.2% (28/45; 95% CI: 47.6%-74.9%), p = 0.034. Inter-observer agreement was substantial for assigning LR-5 on both CEUS and CE-MRI. For both reviewers, there was a higher frequency of LR-5 (44.0% vs. 25.0%, p = 0.009; 42.9% vs. 26.2%, p = 0.023) in CEUS compared with CE-MRI. Arterial phase hyper-enhancement (APHE) was less frequently observed on CEUS than on CE-MRI (46.4% vs. 61.9%, p = 0.044). However, the washout appearance was observed more frequently on CEUS than on CE-MRI (50.0% vs. 28.6%, p = 0.004). Inter-observer agreement between the two reviewers on APHE and washout appearance was excellent for both CEUS and CE-MRI. These findings suggest that CEUS had a much higher sensitivity than CE-MRI in the diagnosis of HCC using LI-RADS, and although the frequencies of major features differed, inter-observer agreement between the two reviewers on major features of HCC was excellent for both CEUS and CE-MRI.

Susceptibility of epithelial tumour cell lines to hyperthermia.

BACKGROUND: Human skin or mucosa exposes cells to both an internal and exogeneous thermal environment and the cells survive within a certain range of temperature. Exogeneous hyperthermia has been applied for the treatment of various types of cancers, fungal disease, and warts. OBJECTIVES: To determine whether different cellular components in the skin adapt to hyperthermic conditions differentially and further elucidate the mechanisms involved. MATERIALS & METHODS: Cell lines derived from normal and tumour epithelial cells were treated with hyperthermic conditions and tested for viability (using an MTS assay), apoptosis (using a FITC-conjugated annexin V apoptosis detection kit), and changes in intracellular calcium (using a calcium-sensitive fluorescent single-wavelength dye, Fluo-4 AM). RESULTS: Thermo-resistance of different cell types was different when cells were subjected to heat at 45̊C for 30 minutes. Stronger effects of hyperthermia were noted on cell viability and apoptosis in epidermal cells relative to their malignant counterparts, except for cell lines harbouring human papillomavirus (HPV). Hyperthermia had a much greater effect on cell viability and apoptosis in a HPV-negative cell line compared to HPV-positive cell lines. We further found that hyperthermia treatment resulted in a strong calcium influx which led to apoptotic cells. However, no obvious increase in apoptosis was observed in cells treated with the CRAC channel selective inhibitor, BTP2, before application of hyperthermia in all cell types, except three cervical cell lines harbouring HPV. CONCLUSION: We propose that hyperthermia results in a CRAC-related strong calcium influx which induces apoptosis, with the exception of HPV-positive cells.

Neuroprotective Effects of a PSD-95 Inhibitor in Neonatal Hypoxic-Ischemic Brain Injury.

The postsynaptic density-95 inhibitor NA-1 uncouples NMDA glutamate receptors from downstream neurotoxic signaling pathways without affecting normal glutamate receptor function. NA-1 attenuates NMDA receptor-mediated neuronal cell death after stroke in multiple models and species. However, its efficacy in providing neuroprotection in models of neonatal hypoxic-ischemic brain injury has not yet been tested. In this study, a modified version of the Rice-Vannucci method for the induction of neonatal hypoxic-ischemic brain injury was performed on postnatal day 7 mouse pups. Animals received a single dose of NA-1 intraperitoneally either before or after right common carotid artery occlusion. All experiments were performed in a blinded manner. Infarct volumes were measured 1 and 7 days after the injury, while behavioral tests were conducted 1, 3, and 7 days after injury. Administration of NA-1 before right common carotid artery occlusion or immediately after ischemia significantly reduced infarct volume and improved neurobehavioral outcomes 1, 3, and 7 days post-injury. The neuroprotection and improvement in neurobehavioral outcomes conferred by NA-1 in this mouse neonatal hypoxic-ischemic injury model imply that NA-1 will be effective in reducing neonatal stroke damage and thus could potentially serve as a therapeutic drug for prevention or treatment of neonatal stroke.

Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.

Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury.

Podoplanin­positive cancer cells at the edge of esophageal squamous cell carcinomas are involved in invasion.

Podoplanin (PDPN) is a well established lymphatic endothelial marker and has frequently been observed in cancer cells at the edge of cancer masses. Previous studies investigating the association between PDPN expression and patient prognosis have had contradictory results. In the present study, it was hypothesized that the different locations of PDPN­positive cells may explain these varying results. The present study aimed to focus on PDPN expression at the edge of esophageal cancer cell nests. In order to analyze the clinical significance of this PDPN expression, immunohistochemistry was performed using esophageal cancer tissue microarrays. PDPN expression at the edge of the cancer cell nest was found to be significantly associated with invasion (P<0.05) and poor prognosis (P<0.001) in patients with cancer. To further investigate the role of PDPN expression in cancer cells, the PDPN gene was cloned and transfected into esophageal squamous cell carcinoma (ESCC) cell lines. PDPN expression was also knocked down using small interfering RNA. PDPN­positive cancer cells were found to exhibit invasion characteristics. Thus, PDPN expression at the edge of a cancer cell nest may indicate invasion and represent a poor prognostic factor for ESCCs.

G4LDB: a database for discovering and studying G-quadruplex ligands.

The G-quadruplex ligands database (G4LDB, http://www.g4ldb.org) provides a unique collection of reported G-quadruplex ligands to streamline ligand/drug discovery targeting G-quadruplexes. G-quadruplexes are guanine-rich nucleic acid sequences in human telomeres and gene promoter regions. There is a growing recognition for their profound roles in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Ligands that affect the structure and activity of G-quadruplexes can shed light on the search for G-quadruplex-targeting drugs. Therefore, we built the G4LDB to (i) compile a data set covering various physical properties and 3D structure of G-quadruplex ligands; (ii) provide Web-based tools for G-quadruplex ligand design; and (iii) to facilitate the discovery of novel therapeutic and diagnostic agents targeting G-quadruplexes. G4LDB currently contains >800 G-quadruplex ligands with ∼4000 activity records, which, to our knowledge, is the most extensive collection of its kind. It offers a user friendly interface that can meet a variety of data inquiries from researchers. For example, ligands can be searched for by name, molecular properties, structures, ligand activities and so on. Building on the reported data, the database also provides an online ligand design module that can predict ligand binding affinity in real time.

[Expression of fascin in human esophageal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To investigate the role of fascin, an actin bundling protein, in the development and progression of human esophageal squamous cell carcinoma (ESCC), and explore its association with the clinicopathologic characteristics and 5-year survival of the patients. METHODS: Using tissue array and immunohistochemistry, the expression of fascin was determined in 241 ESCC tissues and the corresponding normal esophageal mucosal tissues. RESULTS: ESCC tissues showed a significantly higher overexpression rate of fascin than the corresponding normal esophageal mucosal tissues (68.9% vs 15.5%, P<0.05). The overexpression of fascin was correlated to lymph node metastasis and TMN stage, but not to the patients' age, gender, tumor differentiation and general classification. Survival analysis showed that abnormal expression of fascin was associated with the 5-year survival rate of patients with ESCC. CONCLUSIONS: The abnormal expression of fascin may play an important role in the progression of ESCC, and detection of fascin expression may have important prognostic values.