Protect the recurrent laryngeal nerves in US-guided microwave ablation of thyroid nodules at Zuckerkandl tubercle: a pilot study.

BACKGROUND: To evaluate the safety and efficacy of US-guided microwave ablation in patients with thyroid nodules at Zuckerkandl tubercle. METHODS: 103 consecutive patients with thyroid nodules at Zuckerkandl tubercle (ZTTN) were enrolled in this study from November 2017 to August 2021. Prior to the surgery or US-guided microwave ablation (MWA), preoperative ultrasound visualization of the recurrent laryngeal nerve (RLN) and ZTTN was performed, the size and the position relationship between them were observed. Patients were followed up at 1, 3, 6, and 12 months after MWA and the volume reduction rates (VRR) of the thyroid nodules were analyzed. RESULTS: All patients successfully had the RLN and ZTTN detected using ultrasound before surgery or ablation with a detection rate of 100%. For the 103 patients, the majority of ZTTN grades were categorized as grade 2, with the distance from the farthest outside of ZTTN to the outer edge of thyroid ranging between 6.0 and 10.0 mm. The position relationship between ZTTN and RLN was predominantly type A in 98 cases, with type D observed in 5 cases. After MWA, the median nodule volume had significantly decreased from 4.61 (2.34, 8.70) ml to 0.42 (0.15, 1.41) ml and the VRR achieved 84.36 ± 13.87% at 12 months. No nodules regrew throughout the 12-month follow-up period. Of the 11 patients experienced hoarseness due to RLN entrapment before ablation, 7 recovered immediately after separation of the RLN and ZTTN during MWA, 2 recovered after one week, and the other 2 recovered after two months. CONCLUSIONS: The RLN is closely related to ZTTN and mainly located at the back of ZTTN. The RLN can be separated from ZTTN by hydrodissection during MWA. US-guided MWA is a safe and effective treatment for ZTTN.

Ultrasound-guided percutaneous thermal ablation of parotid tumors: experience from two-centers.

Objective: To evaluate the efficacy and feasibility of ultrasound-guided percutaneous thermal ablation (TA) for treating benign parotid tumors.Methods: Patients with benign parotid tumors who underwent ultrasound-guided microwave ablation (MWA) or radiofrequency ablation (RFA) between January 2020 and March 2023 were included in this retrospective study. Change in tumor size (maximum diameter, tumor volume(V), volume reduction rate (VRR)) and cosmetic score (CS) were evaluated during a one-year follow-up period. We also recorded the incidence of any complications associated with TA.Results: A total of 23 patients (13 males and 10 females; median age 65 years, range 5-91 years) were included. The mean VRR at 1, 3, 6, and 12 months after TA was 37.03%±10.23%, 56.52%±8.76%, 82.28%±7.89%, and 89.39%±6.45%, respectively. Mean CS also changed from 3.39 ± 0.66 to 1.75 ± 0.93 (p < 0.001) by the end of follow-up time. Subgroup analysis showed that tumors with smaller initial maximum diameter had a faster CS reduction rate than those with larger initial diameter. The incidence of facial nerve dysfunction was 8.70%.Conclusion: Ultrasound-guided percutaneous TA is an effective and safe treatment option for patients with benign parotid tumors.

Multi-Omics Analysis of the Prognostic and Immunological Role of Runt-Related Transcription Factor 3 in Pan-Cancer.

Runt-related transcription factor 3 (RUNX3) plays a pivotal role in tumor microenvironment and immune infiltration. However, the prognostic and immunological roles of RUNX3 in pancancer remain unclear. In the current study, we explored the expression profiles, prognostic landscape, and immune infiltration of RUNX3 in pancancer through a variety of online platforms, including HPA, ONCOMINE, UALCAN, GEPIA, PrognoScan, TCGA, TIMER, R2, and Reactome databases. In general, RUNX3 was widely expressed in tonsil, gallbladder, skin, spleen, lymph node, and bone marrow, and RUNX3 was frequently higher expression in tumor tissues compared to normal tissues. In prognostic analysis, the RUNX3 expression level was significantly correlated with the clinical outcomes of bladder cancer, blood cancer, brain cancer, breast cancer, colorectal cancer, lung cancer, and ovarian cancer. In mutation analysis, a total 72 mutation sites were located within amino acids 1 to 415 of RUNX3, including 65 missense sites and seven truncating sites, whereas the mutation frequency of skin cutaneous melanoma and uterine corpus endometrial carcinoma (UCEC) is relatively high (> 3%). In immune infiltration analysis, the RUNX3 expression level was significantly related to recognized markers and the immune infiltration levels of various types of immune cells in colon adenocarcinoma (COAD) and brain lower grade glioma (LGG). After that, 453 RUNX3 co-expressed genes were recognized in COAD, lymphoid neoplasm diffuse large B-cell lymphoma, LGG, and ovarian serous cystadenocarcinoma (OV). Pathway enrichment analysis revealed that RUNX3 co-expressed genes were remarkably enriched in immune system and tumor progression pathways. RUNX3 expression is associated with clinical prognosis, immune infiltration, and identified RUNX3 related pathways in a variety of tumors, which may serve as targets of promising prognostic markers and novel therapeutic targets for various human cancers.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Value of transrectal ultrasound-guided biopsy in endoscopy negative biopsy patients with rectal lesions.

OBJECTIVE: To evaluate the value of transrectal ultrasound (TRUS) guided biopsy in endoscopy negative biopsy patients with rectal lesions. METHODS: 150 endoscopy negative biopsy result rectal lesions adopted the transrectal ultrasound-guided biopsy. Based on whether the patients received contrast-enhanced ultrasound examination or not before the biopsies, all enrolled cases were divided into TRUS guided group and contrast-enhanced TRUS (CE-TRUS) guided group, and the safety and diagnostic performances were analyzed retrospectively. RESULTS: We obtained adequate specimens in the majority of cases (98.7%,148/150); There were no complications identified in our study. 126 patients received contrast-enhanced TRUS examination before biopsy to evaluate vascular perfusion and necrosis. The sensitivity, specificity, PPV, NPV, and overall accuracy of all biopsies were 89.1%, 100%,100%, 70.4%, and 91.3% respectively; The sensitivity, specificity, PPV, NPV, and accuracy for TRUS-guided biopsy and CE-TRUS guided biopsy were 73.7%, 100%,100%, 50%,79.2% and 92.1%,100%,100%,75%,93.6% separately; The increase in correct diagnoses was significant (p < 0.05) between TRUS guided biopsy and CE-TRUS guided biopsy. CONCLUSION: TRUS-guided biopsy is a reliable procedure that can be augmented by endoscopic biopsy techniques if the biopsy yields negative results. CE-TRUS might assist in the location of the biopsy and decrease sampling errors.

Focused ultrasound-mediated blood-brain barrier opening combined with magnetic targeting cytomembrane based biomimetic microbubbles for glioblastoma therapy.

Glioblastoma is the most common type of brain tumor. Due to the presence of the blood-brain barrier, the effects of chemotherapy have been unsatisfactory. The combination of focused ultrasound and microbubbles to reversibly open the blood-brain barrier is now considered a key factor in improving treatment outcomes of glioblastoma. In this study, we developed bionic drug delivery microbubbles, which in combination with focused ultrasound had an obvious inhibitory effect on glioblastoma. We extracted the brain microvascular cell membranes, combined them with lipid components, and loaded them with superparamagnetic iron oxide and doxorubicin to prepare biomimetic drug delivery microbubbles (FeDOX@cellMBs). We demonstrated that FeDOX@cellMBs retained the intrinsic properties of loading, such as magnetic properties and drug toxicity, both in vitro and in vivo. FeDOX@cellMBs exhibited good tumor targeting and uptake under the combined action of magnetic and focused ultrasound. Importantly, the FeDOX@cellMBs demonstrated excellent internal stability and effectively inhibited tumor growth in orthotopic glioblastoma mice. Finally, organ H&E staining confirmed that FeDOX@cellMBs were safe for use. In conclusion, FeDOX@cellMBs successfully penetrated the blood-brain barrier and effectively inhibited glioblastoma growth under the combined effects of focused ultrasound and magnetic stimulation. These results provide a new approach for the treatment of glioblastoma, with implications for future clinical translation.

Comparison of ultrasound-guided microwave ablation and ultrasound-guided vacuum-assisted excision for treating breast lesions of uncertain malignant potential (B3 lesions): A retrospective study.

AIMS: To compare the safety and therapeutic effect of ultrasound (US)-guided microwave ablation (MWA) and US-guided vacuum-assisted excision (VAE) for patients with B3 lesions of the breast. METHODS: Patients who underwent US-guided MWA or US-guided VAE at Sichuan Tumor Hospital from January 2016 to December 2021 were retrospectively analyzed. The technical success rate and residual rate of the two minimally invasive surgeries were recorded. During follow-up, differences in symptom relief, recurrence or progression, re-intervention, incidence of adverse events, or personal satisfaction were observed between the two groups. RESULTS: The follow-up time was comparable between the two groups. The technical success rate was similar between the two groups; no residue was found in the US-guided MWA group, and the residue rate in the US-guided VAE group was 3.4%. The symptoms of the two groups were improved after the operation. The incidence of postoperative adverse events in the US-guided MWA group was significantly lower than that in the US-guided VAE group. Additionally, the MWA group had a lower incidence of adverse events when the tumor diameter was >2.5 cm. Compared to the US-guided VAE group, the US-guided MWA group had a lower rate of tumor recurrence or progression, re-intervention rate, and higher personal satisfaction. CONCLUSIONS: The technical success rate of US-guided MWA for B3 lesions was comparable to that of US-guided VAE, but US-guided MWA had a lower incidence of adverse events and a higher degree of personal satisfaction compared with US-guided VAE.

Simultaneous sludge minimization and membrane fouling mitigation in membrane bioreactors by using a microaerobic - Settling pretreatment module.

Membrane fouling is the major obstacle for membrane bioreactors operated at a long sludge retention time to reduce sludge production. In this study, a sludge process reduction (SPR) module, consisting of a microaerobic tank and a settler, was inserted before an anoxic/oxic MBR (AO-MBR) to achieve dual objectives of fouling alleviation and sludge reduction. Three SPR-MBRs were operated to investigate influences of sludge recirculation ratios from the SPR settler to the microaerobic tank on process performance. Compared to AO-MBR, the SPR-MBRs reduced sludge production by 43.1-56.4% by maintaining sludge retention times above 175 d, and decreased foulant layer resistance and pore clogging resistance. Inserting SPR reduced the accumulation of dissolved organic matters and extracellular polymeric substances, enlarged sludge flocs, and decreased sludge viscoelasticity. However, increasing RSPR stimulated outward diffusion of extracellular polymeric substances and increased sludge viscosity. SPR-MBRs achieved effective sludge reduction by enriching hydrolytic (Trichococcus and Aeromonas) and fermentative genera (Lactococcus, Paludibacter, Macellibacteroides, and Acinetobacter) in the SPR, and alleviated membrane fouling by prohibiting the growth of extracellular polymeric substance-secreting bacteria and enriching filamentous bacteria to enlarge particle size. The results revealed that the SPR-MBR maximized sludge reduction with a very long sludge retention time, and alleviated membrane fouling synchronously.

The value of preoperative sentinel lymph node contrast-enhanced ultrasound for breast cancer: a large, multicenter trial.

OBJECTIVE: The study conducted a multicenter study in China to explore the learning curve of contrast enhanced ultrasound (CEUS) for sentinel lymph nodes (SLNs), the feasibility of using this technique for the localization of SLNs and lymphatic channels (LCs) and its diagnostic performance for lymph node metastasis. METHOD: Nine hundred two patients with early invasive breast cancer from six tertiary class hospitals in China were enrolled between December 2016 and December 2019. Each patient received general ultrasound scanning and SLN-CEUS before surgery. The locations and sizes of LCs and SLNs were marked on the body surface based on observations from SLN-CEUS. These body surface markers were then compared with intraoperative blue staining in terms of their locations. The first 40 patients from each center were included in determining the learning curve of SLN-CEUS across sites. The remaining patients were used to investigate the diagnostic efficacy of this technique in comparison with intraoperative blue staining and pathology respectively. RESULT: The ultrasound doctor can master SLN-CEUS after 25 cases, and the mean operating time is 22.5 min. The sensitivity, specificity, negative predictive value, and positive predictive value of SLN-CEUS in diagnosing lymph node metastases were 86.47, 89.81, 74.90, and 94.97% respectively. CONCLUSION: Ultrasound doctors can master SLN-CEUS with a suitable learning curve. SLN-CEUS is a feasible and useful approach to locate SLNs and LCs before surgery and it is helpful for diagnosing LN metastases.

Metabolic Adaptation of a Globally Important Diatom following 700 Generations of Selection under a Warmer Temperature.

Diatoms, accounting for 40% of the marine primary production and 20% of global carbon dioxide fixation, are threatened by the ongoing ocean warming (OW). However, whether and how these ecologically important phytoplankton adapt to OW remains poorly unknown. Here, we experimentally examined the metabolic adaptation of a globally important diatom species Skeletonema dohrnii (S. dohrnii) to OW at two elevated temperatures (24 and 28 °C compared with 20 °C) under short-term (∼300 generations) and long-term (∼700 generations) selection. Both warming levels significantly increased the cell growth rate but decreased the chlorophyll a content. The contents of particulate organic carbon (POC) and particulate organic nitrogen (PON) decreased significantly initially (i.e., until 300 generations) at two temperature treatments but completely recovered after 700 generations of selection, suggesting that S. dohrnii ultimately developed thermal adaptation. Proteomic analysis demonstrated that elevated temperatures upregulated energy metabolism via glycolysis, tricarboxylic acid cycle, and fatty acid oxidation as well as nitrogen acquisition and utilization, which in turn reduced substance storage because of trade-off in the 300th generation, thus decreasing POC and PON. Interestingly, populations at both elevated temperatures exhibited significant proteome plasticity in the 700th generation, as primarily demonstrated by the increased lipid catabolism and glucose accumulation, accounting for the recovery of POC and PON. Changes occurring in cells at the 300th and 700th generations demonstrate that S. dohrnii can adapt to the projected OW, and readjusting the energy metabolism is an important adaptive strategy.

2022 Expert consensus on the use of laser ablation for papillary thyroid microcarcinoma.

OBJECTIVE: With the aim of standardizing and improving the use of ultrasound-guided PLA on PTMC, a panel of experts from China and Italy, jointly issued this expert consensus on the clinical use of PLA for low-risk PTMC. METHODS: This expert consensus was developed by Chinese and Italian experts who have specific competence and expertise in this area. An evidence-based approach combining the knowledge and practical experience of the panelists was utilized. RESULTS: Twenty-six expert consensus recommendations were developed, spanning topics including the indications and contraindications of PLA for PTMC, physician training, preoperative preparation of patients, intraoperative technical procedures, possible complications, efficacy assessment, follow-up strategy, the approach to new PTMC and metastatic lymph nodes after treatment, thyroid-stimulating hormone inhibition therapy, and quality control of the entire procedure. CONCLUSION: We summarized practical recommendations about standardized and improved PLA treatment for PTMC.

Comparative study on efficacy and safety of ultrasound guided transoral and transcutaneous core needle biopsy in patients with oral masses.

BACKGROUND: Ultrasound (US) guided transoral biopsy is a novel and safe procedure for obtaining tissue in patients with oral masses. However, this procedure is less commonly used in comparison to US guided transcutaneous biopsy. The aim of this study is to compare the efficacy and safety of US-guided transoral and transcutaneous core needle biopsy (CNB) in patients with oral masses. METHODS: From November 2019 to March 2021, consecutive patients with oral masses were randomly assigned to undergo US-guided transoral CNB (transoral group) and US-guided transcutaneous CNB from a submental approach (transcutaneous group). During the operation, procedure time, intra­operative blood loss volume, diagnostic performance, rate of complications and pain level were recorded and compared. RESULTS: There were 112 patients (62 in the transoral group and 50 in the transcutaneous group) evaluated in this study. The postprocedural complication rate of the transcutaneous group was significantly higher than the transoral group (24% vs. 0%, P = 0.000). There was no significant difference in accuracy (95.2% vs. 88%, P = 0.30), biopsy time (76 ± 12 s vs. 80 ± 13 s, p = 0.09), blood losses (2.6 ± 0.5 mL vs. 2.7 ± 0.4 mL, p = 0.17) and visual analogue score (p = 0.327 and p = 0.444 before and after the sampling procedure) between the two groups. CONCLUSION: US-guided transoral CNB results in high rates of technical success and lower rates of postprocedural complications.

The Value of IOTA Simple Rules Combined With CEUS Scoring System in the Diagnosis of Benign and Malignant Ovarian Masses and Its Correlation With MVD and VEGF: A Preliminary Study.

OBJECTIVES: To investigate the diagnostic value of International Ovarian Tumor Analysis (IOTA) simple rules combined with contrast-enhanced ultrasound (CEUS) scoring system in the differential diagnosis of ovarian tumors, and the correlations of the scoring system with microvessel density (MVD) and vascular endothelial growth factor (VEGF). METHODS: One hundred eighty-nine patients with ovarian tumors were examined by routine ultrasound and CEUS. The enhanced characteristics of CEUS were observed, and the masses were classified by IOTA simple rules. To compare the diagnostic value of IOTA simple rules combined with CEUS scoring system and IOTA simple rules in the diagnosis of ovarian tumors. Immunohistochemistry was used to detect the expression of MVD and VEGF in postoperative tissue samples. The correlations between the new scoring system with MVD and VEGF were analyzed. RESULTS: The sensitivity (93.98%), specificity (94.34%), positive predictive value (92.86%), negative predictive value (95.24%), and accuracy (94.18%) of IOTA simple rules combined with CEUS scoring system in the diagnosis of ovarian tumors were higher than those of IOTA simple rules alone (all P < .05). The score system was significantly positively correlated with MVD and VEGF, and the r values were 0.77 and 0.63, respectively (P < .001). CONCLUSIONS: IOTA simple rules combined with CEUS scoring system was helpful to improve the accuracy of ultrasound diagnosis of ovarian tumors, which was significantly correlated with MVD and VEGF. It could provide important reference information for treatment scheme formulation and prognosis evaluation.

Rapid solid phase microextraction of DNA using mesoporous metal-organic framework coating for PCR-based identification of meat adulteration.

A rapid, convenient, low-cost, and selective DNA isolation method was developed for identifying meat adulteration. A mesoporous metal organic framework (Meso-UIO-66)-coated solid phase microextraction system was employed as an isolation device to simplify DNA isolation into three steps (lysis, washing, and elution). Meso-UIO-66 was utilized as the adsorbent because of its positively charged surface, high chemical stability, and mesoporous structure. Meso-UIO-66 was characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet‒visible spectroscopy, X-ray photoelectron spectroscopy, and nitrogen adsorption-desorption tests. Parameters that affected DNA isolation were optimized. This method can be used to isolate and purify DNA from meat in 60 s, and the DNA concentration and purity are comparable to those of samples isolated with a commercial kit. Multiple DNA detection was achieved by coupling this method with the multiplex polymerase chain reaction technique, and the detection limit was lower than 1% (w/w).

Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells.

Shikonin is the main component of root extracts from the Chinese herbal medicine Lithospermum erythrorhizon, which is commonly used for the treatment of various diseases including cancer. Previous research showed that shikonin suppressed pancreatic cancer growth; nevertheless, its molecular targets and mechanisms have not been elucidated. This study aimed to investigate the interaction and regulatory mechanisms of shikonin on its potential target p21-activated kinase 1 (PAK1). Through a labchip-based screening method, shikonin was identified as a potential bioactive PAK1 inhibitor. Molecular docking technology was used to detect the interaction sites of shikonin and PAK1 kinase. Western blot was performed to validate the mechanism. MTT and flow cytometry were practiced to investigate the effect of shikonin against pancreatic cancer cells. The results show that shikonin significantly inhibited the activity of PAK1 kinase with IC50 value of 7.252 ± 0.054 µM. Molecular docking studies showed that shikonin binds to the ATP-binding pocket of the PAK1 kinase domain. Moreover, shikonin inhibited PAK1 activation and its downstream signaling pathway proteins, while reducing proliferation and inducing apoptosis of pancreatic cancer cells. Further studies showed that the treatment of shikonin sensitized pancreatic cancer cells to chemotherapeutic drugs. These results suggest that shikonin, a potential natural inhibitor targeting PAK1 kinase, has promising potent applications in the treatment of pancreatic cancer and chemotherapy sensitization.

A preliminary study on ultrasound-guided percutaneous microwave ablation for palliative treatment of advanced head and neck malignancies.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound (US)-guided percutaneous microwave ablation (UgPMWA) for palliative treatment of advanced head and neck malignancies. MATERIALS AND METHODS: This study includes 18 consecutive patients with advanced head and neck malignancies (n = 24), who have undergone UgPMWA for palliative treatment at our institution from December 2016 to April 2020. The maximum diameter and volume of the tumor were assessed by US, CT or MRI before microwave ablation (MWA), 1, 3 and 6 months after MWA and every 6 months thereafter. The quality of life was clinically assessed by the University of Washington Head and Neck Quality of Life questionnaire (UW-QOl). RESULTS: The success rate of tumor-targeting microwave antenna placement was 100%. No nerve injury and serious complications or death occurred during the perioperative period. The follow-up duration varied from 1 month to 38 months (11.56 ± 10.23 months) among patients. By the last follow-up before submission, the value of maximum diameter (5.00 ± 2.90 vs 3.28 ± 2.11 cm. p < 0.05) and tumor volume decreased significantly（74.35 ± 46.88 vs 47.45 ± 24.08 cm3. p < 0.05）respectively after palliative treatment with UgPMWA. UW-QOl of the patients was improved (59.24 ± 11.51 vs 69.84 ± 8.12, p < 0.05). CONCLUSION: UgPMWA is safe and effective for the palliative treatment of head and neck malignancies. Ultrasonic guidance can indicate an accurate location of the microwave antenna. It can also monitor the ablation area in real-time during the operation to avoid damage to surrounding normal tissues.

The concordance in lesion detection and characteristics between the Anatomical Intelligence and conventional breast ultrasound Scan method.

BACKGROUND: The aim of this study was to investigate the concordance in lesion detection, between conventional Handhold Ultrasound (HHUS) and The Anatomical Intelligence for Breast ultrasound scan method. RESULT: The AI-breast showed the absolute agreement between the resident and an experienced breast radiologist. The ICC for the scan time, number, clockface location, distance to the nipple, largest diameter and mean diameter of the lesion obtained by a resident and an experienced breast radiologist were 0.7642, 0.7692, 0.8651, 0.8436, 0.7502, 0.8885, respectively. The ICC of the both practitioners of AI-breast were 0.7971, 0.7843, 0.9283, 0.8748, 0.7248, 0.8163, respectively. The k value of Anatomical Intelligence breast between experienced breast radiologist and resident in these image characteristics of boundary, morphology, aspect ratio, internal echo, and BI-RADS assessment were 0.7424, 0.7217, 0.6741, 0.6419, 0.6241, respectively. The k value of the two readers of AI-breast were 0.6531, 0.6762, 0.6439, 0.6137, 0.5981, respectively. CONCLUSION: The anatomical intelligent breast US scanning method has excellent reproducibility in recording the lesion location and the distance from the nipple, which may be utilized in the lesions surveillance in the future.

Long-Acting Human Growth Hormone Receptor Antagonists Produced in E. coli and Conjugated with Polyethylene Glycol.

Growth hormone (GH) is a peptide hormone that mediates actions through binding to a cell surface GH receptor (GHR). The GHR antagonist, B2036, combines an amino acid substitution at 120 that confers GHR antagonist activity, with eight additional amino acid substitutions. Conjugation to polyethylene glycol (PEG) increases the serum half-life of these proteins due to reduced renal clearance. Recombinant forms of GH and its antagonists are mainly produced in prokaryotic expression systems, such as E. coli. However, efficient production in E. coli is problematic, as these proteins form aggregates as inclusion bodies resulting in poor solubility. In the present study, we demonstrate that N-terminal fusion to a thioredoxin (Trx) fusion partner improves soluble expression of codon-optimized B2036 in E. coli when expressed at 18 °C. Expression, purification and PEGylation protocols were established for three GHR antagonists: B2036, B20, and G120Rv. Following purification, these antagonists inhibited the proliferation of Ba/F3-GHR cells in a concentration-dependent manner. PEGylation with amine-reactive 5 kDa methoxy PEG succinimidyl propionate yielded a heterogeneous mixture of conjugates containing four to seven PEG moieties. PEGylation significantly reduced in vitro bioactivity of the conjugates. However, substitution of lysine to arginine at amino acid residue 120 in B2036 improved the in vitro activity of the PEGylated protein when compared to unmodified PEGylated B2036. Pharmacokinetic analysis demonstrated that the circulating half-life of PEGylated B20 was 15.2 h in mice. Taken together, we describe an effective strategy to produce biologically active PEGylated human GHR antagonists.

Ameliorative effect of Albizia chinensis synthesized ZnO-NPs on Mycoplasma pneumoniae infected pneumonia mice model.

BACKGROUND: Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) among the children and adults that results upper and lower respiratory tract infections. OBJECTIVE: This study was aimed to inspect the ameliorative action of A. chinensis synthesized ZnONPs against M. pneumoniae infected pneumonia mice model. MATERIALS AND METHODS: ZnO NPs was synthesized from Albizia chinensis bark extract and characterized by UV-Vis spectroscopy, Fourier Transform Infrared (FTIR), Transmission Electron Microscopy (TEM), energy dispersive X-ray (EDX) and atomic force microscope (AFM) analyses. The antibacterial effectual of synthesized ZnONPs were examined against clinical pathogens. The pneumonia was induced to BALB/c mice via injecting the M. pneumoniae and treated with synthesized ZnONPs, followed by the total protein content, total cell counts and inflammatory mediators level was assessed in the BALF of experimental animals. The Histopathological investigation was done in the lung tissues of test animals. RESULTS: The outcomes of this work revealed that the formulated ZnONPs was quasi-spherical, radial and cylindrical; the size was identified as 116.5 ± 27.45 nm in diameter. The in vitro antimicrobial potential of formulated ZnO-NPs displayed noticeable inhibitory capacity against the tested fungal and bacterial strains. The administration of synthesized ZnO-NPs in MP infected mice model has significantly reduced the levels of total protein, inflammatory cells, inflammatory cytokines such as IL-1, IL-6, IL-8, tumour necrosis factor-alpha (TNF-a) and transforming growth factor (TGF). Besides, the histopathological examination of MP infected mice lung tissue showed the cellular arrangements were effectively retained after administration of synthesized ZnO-NPs. CONCLUSION: In conclusion, synthesized ZnO-NPs alleviate pneumonia progression via reducing the level of inflammatory cytokines and inflammatory cells in MP infected mice model.

Contrast-enhanced ultrasound-guided celiac plexus neurolysis in patients with upper abdominal cancer pain: initial experience.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of contrast-enhanced ultrasound (CEUS)-guided celiac plexus neurolysis (CPN) in patients with upper abdominal cancer pain. METHODS: Thirty-five patients with upper abdominal cancers tortured by intractable upper abdominal pain underwent CEUS-guided CPN with ethanol. The pain alleviation and opioid intake were observed and evaluated during a 3-month follow-up after CPN. The dispersion of alcohol around the aorta was evaluated on 3D-CEUS. Complications were assessed during CPN and at follow-up. RESULTS: All of the 35 patients' CPN was successfully achieved. Pain relief was observed in 28 (80%), 20 (57.1%), 27 (77.1%), 20 (57.1%), and 10 (29.4%) patients immediately, 1 day, 1 month, 2 months, and 3 months after CPN, respectively. The agent dispersion around the aorta on CEUS images of 28 patients who showed pain relief was at least 90° of the circumference around the aorta. The median duration of pain alleviation was 2.7 months (95% confidence interval [CI], 2.5-2.9). Less than half of the patients had minor complications including irritant pain at the puncture site (8 of 35; 22.9%), diarrhea (4 of 35; 11.4%), nausea and vomiting (3 of 35; 8.6%), and post-procedural hypotension (1 of 35; 2.9%). CONCLUSIONS: CEUS-guided CPN is a safe and effective method to alleviate refractory upper abdominal pain in patients with upper abdominal cancers. CEUS image allows the visualization of puncture path and observation of drug dispersion. The pain relief is relevant to the dispersion of neurolytic agent around the aorta. KEY POINTS: • CEUS-guided celiac plexus neurolysis (CPN) is feasible and easy. • It allows direct visualization of the diffusion of the neurolytic agent in the retroperitoneal anatomic space. • CEUS-guided CPN improves safety of CPN by clearly delineating the needle path.