The role of EUS-guided iodine-125 seed implantation in patients with unresectable ampullary cancer after relief of obstructive jaundice.

Purpose: Few studies have focused on the management of inoperable ampullary carcinoma (AC), and patients with jaundice suffer from biliary stents replacement frequently. Iodine-125 (125I) brachytherapy has been used in the treatment of malignant tumors owing to its curative effect, minimal surgical trauma, and tolerable complications. The aim of the study was to investigate the role of 125I seed implantation in patients with unresectable ampullary carcinoma after relief of obstructive jaundice. Material and methods: A total of 44 patients with obstructive jaundice resulting from unresectable ampullary carcinoma from January 1, 2010 to October 31, 2020 were enrolled in the study. Eleven patients underwent implantation of 125I seeds under endoscopic ultrasound (EUS) after receiving biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) (treatment group), and 33 patients received a stent alone via ERCP (control group). Cox regression model was applied in this single-center retrospective comparison study. Results: The median maximum intervention interval for biliary obstruction was 381 days (interquartile range [IQR]: 204-419 days) in the treatment group and 175 days (IQR: 126-274 days) in the control group (p < 0.05). Stent occlusion rates at 90 and 180 days in the control group were 12.9% and 51.6%, respectively. No stent occlusion occurred in the treatment group. Patients in the treatment group obtained longer survival time (median, 26 vs. 13 months; p < 0.01) and prolonged duodenal obstruction (median, 20.5 vs. 11 months; p < 0.05). No brachytherapy-related grade 3 or 4 adverse events were observed. Conclusions: Longer intervention interval for biliary obstruction and survival as well as better stent patency and prolonged time to duodenal obstruction could be achieved by implanting 125I seeds combined with biliary stent in patients with unresectable ampullary cancer.

Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis.

Purpose: To explore the biliary and duodenal microbiota features associated with the formation and recurrence of choledocholithiasis (CDL). Methods: We prospectively recruited patients with primary (P-CDL, n = 29) and recurrent CDL (R-CDL, n = 27) for endoscopic retrograde cholangiopancreatography (ERCP). Duodenal mucosa (DM), bile and bile duct stones (BDS) samples were collected in P- and R-CDL patients. DM samples were also collected in 8 healthy controls (HC). The microbiota profile analysis was performed with 16S rRNA gene sequencing. Results: Short-course antibiotic application before ERCP showed no significant effects in alpha and beta diversities of the biliary and duodenal microbiota in CDL. Alpha diversity showed no difference between DM and bile samples in CDL. The duodenal microbial richness and diversity was lower in both P- and R-CDL than HC. The biliary microbiota composition showed a high similarity between P- and R-CDL. Fusobacterium and Enterococcus were higher abundant in DM, bile, and BDS samples of R-CDL than P-CDL, as well as Escherichia and Klebsiella in bile samples of R-CDL. The enriched duodenal and biliary bacteria in CDL were closely associated with cholecystectomy, inflammation and liver dysfunction. The bile-associated microbiota of R-CDL expressed enhanced capacity of D-glucuronide and D-glucuronate degradation, implicating an elevated level of ß-glucuronidase probably produced by enriched Escherichia and Klebsiella in bile. Conclusions: The duodenal microbiota was in an imbalance in CDL. The duodenal microbiota was probably the main source of the biliary microbiota and was closely related to CDL formation and recurrence. Enterococcus, Fusobacterium, Escherichia and Klebsiella might contribute to CDL recurrence. Clinical trials: The study was registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html, ChiCTR2000033940). Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00267-2.

Aneurysmal Subarachnoid Hemorrhage and Sex Differences: Analysis of Epidemiology, Outcomes, and Risk Factors.

BACKGROUND: The differences in outcomes after aneurysmal subarachnoid hemorrhage (aSAH) between the sexes have not been concretely determined. This study aimed to evaluate the differences in epidemiology, outcomes, and risk factors between male and female patients with aSAH. METHODS: We performed a multicenter, retrospective study of patients with aSAH from 2017 to 2020. We investigated the epidemiological differences between the two sexes. Propensity score matching (PSM) was used to compare short-term outcomes between the sexes. Binary logarithmic regression was performed to investigate the odds ratio (OR) for dependent survival in patients of different sexes. RESULTS: A total of 5,407 consecutive patients with aSAH were included in this study, and the female-to-male ratio was 1.8:1. The peak incidence of aSAH occurred in the 6th and 7th decades in males and females, respectively. There were more female patients with internal carotid artery or posterior communicating artery aneurysms (53.2%), and there were more male patients with anterior cerebral artery or anterior communicating artery aneurysms (43.2%). The incidence of multiple aneurysms was greater in female patients (21.5% vs. 14.2%, P < 0.001). There was no significant difference in outcomes before and after PSM at discharge. The dependent survival risk was related only to the clinical condition on admission in women. In addition, age > 50 years (OR 1.88, 95% confidence interval 1.17-3.02; P = 0.01) and hypertension (OR 1.81, 95% confidence interval 1.25-2.61; P = 0.002) were also risk factors for male patients. CONCLUSIONS: There were more female patients with aneurysms than male patients in this study. Most aneurysm locations were different between the two groups. There was no significant difference in discharge outcomes before and after PSM. The risk factors for dependent survival were different between female and male patients.

Microfluidic platforms in diagnostic of ovarian cancer.

The most important reason for death from ovarian cancer is the late diagnosis of this disease. The standard treatment of ovarian cancer includes surgery and chemotherapy based on platinum, which is associated with side effects for the body. Due to the nonspecific nature of clinical symptoms, developing a platform for early detection of this disease is needed. In recent decades, the advancements of microfluidic devices and systems have provided several advantages for diagnosing ovarian cancer. Designing and manufacturing new platforms using specialized technologies can be a big step toward improving the prevention, diagnosis, and treatment of this group of diseases. Organ-on-a-chip microfluidic devices are increasingly used as a promising platform in cancer research, with a focus on specific biological aspects of the disease. This review focusing on ovarian cancer and microfluidic application technologies in its diagnosis. Additionally, it discusses microfluidic platforms and their potential future perspectives in advancing ovarian cancer diagnosis.

The association of carbohydrate antigen 19-9 response with radiologic response and survival in intrahepatic cholangiocarcinoma: A prospective cohort study.

BACKGROUND: The role of carbohydrate antigen 19-9 (CA 19-9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of the CA 19-9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA. METHODS: A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19-9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19-9 response and the radiologic response was performed. The associations between CA 19-9 response and imaging response, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Two hundred sixty-seven patients (63.3%) had a CA 19-9 response. A CA 19-9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19-9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio [HR], 4.8 months; 95% confidence interval [CI], 3.8-6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2-6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19-9 nonresponder status, and radiologic nonresponder status in multivariable analysis. CONCLUSIONS: CA 19-9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19-9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies. PLAIN LANGUAGE SUMMARY: A decline in carbohydrate antigen 19-9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells.

The inflammation of the pancreatic islets triggers ß cell dysfunction and type 2 diabetes mellitus (T2DM) onset. While dietary lycopene consumption contributes to protection against T2DM in animal studies, the potential mechanism of this compound in the regulation of islet function in T2DM remains largely unclear. In this study, by using anti-diabetic metformin as a positive control, we demonstrated that lycopene treatment suppressed islet inflammation and apoptosis in both high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice and in Min6 cells exposed to high glucose/palmitic acid (HG/PA)-RAW264.7 conditioned medium. Lycopene intervention resulted in M1/M2 macrophage polarization homeostasis, which is associated with increased insulin secretion, decreased fasting blood glucose levels, and improved lipid profiles in diabetic mice. Furthermore, the protective actions of lycopene were associated with the down-regulation of the TLR4/MyD88/NF-κB signaling pathway, which is positively related to inflammation in both diabetic mice and Min6 cells. Collectively, our findings indicated that lycopene ameliorates islet function and apoptosis and attenuates hyperglycemia and dyslipidemia by the regulation of the TLR4/MyD88/NF-κB signaling pathway. This study highlights dietary lycopene consumption as a novel strategy for the management of patients with diabetes.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine.

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.

ß-Cryptoxanthin Attenuates Cigarette-Smoke-Induced Lung Lesions in the Absence of Carotenoid Cleavage Enzymes (BCO1/BCO2) in Mice.

High dietary intake of ß-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) and ß-carotene-9',10'-oxygenase (BCO2) to produce retinol and apo-10'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-ß-apo-10'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.

Bioengineered materials with selective antimicrobial toxicity in biomedicine.

Fungi and bacteria afflict humans with innumerous pathogen-related infections and ailments. Most of the commonly employed microbicidal agents target commensal and pathogenic microorganisms without discrimination. To distinguish and fight the pathogenic species out of the microflora, novel antimicrobials have been developed that selectively target specific bacteria and fungi. The cell wall features and antimicrobial mechanisms that these microorganisms involved in are highlighted in the present review. This is followed by reviewing the design of antimicrobials that selectively combat a specific community of microbes including Gram-positive and Gram-negative bacterial strains as well as fungi. Finally, recent advances in the antimicrobial immunomodulation strategy that enables treating microorganism infections with high specificity are reviewed. These basic tenets will enable the avid reader to design novel approaches and compounds for antibacterial and antifungal applications.

Portal vein embolization for closure of marked arterioportal shunt of hepatocellular carcinoma to enable radioembolization: A case report.

BACKGROUND: Marked arterioportal shunt (APS) can be a contraindication for transarterial radioembolization (TARE) because of the risk of radiation-induced liver toxicity or pneumonitis. To date, the best method to close marked APS to reduce intrahepatic shunt (IHS) and hepatopulmonary shunt (HPS) before TARE has not been elucidated. CASE SUMMARY: This case report describes a novel strategy of embolization of the portal venous outlet to reduce IHS and HPS caused by marked APS before TARE in a patient with advanced hepatocellular carcinoma (HCC). The patient had a significant intratumoral shunt from the tumor artery to the portal vein and had already been suspected based on pre-interventional magnetic resonance angiography, and digital subtraction angiography (DSA) confirmed the shunt. Selective right portal vein embolization (PVE) was performed to close the APS outlet and DSA confirmed complete closure. Technetium-99m macroaggregated albumin was administered and single photon emission computed tomography revealed a low HPS with 8.4%. Successful TARE was subsequently performed. No major procedure-related complication occurred. CONCLUSION: Closure of APS with PVE during mapping angiography of advanced-stage HCC to enable reduction of HPS and subsequent TARE is feasible.

Comparison of the Therapeutic Effects of Iodine-125 Seed Implantation and Conventional Radiochemotherapy for Advanced Esophageal Cancer.

BACKGROUND: The purpose of this study was to explore the feasibility, safety and efficacy of iodine-125 seed implantation in the treatment of dysphagia of advanced esophageal cancer. METHODS: We retrospectively analyzed patients with advanced esophageal cancer who underwent EUS-guided iodine-125 seed implantation or conventional chemoradiotherapy in our hospital. The propensity score match was used to reduce the baseline differences. RESULTS: A total of 127 patients were enrolled, 17 patients received EUS-guided iodine 125 seed implantation (Group A), 31 patients received radiotherapy (Group B), 38 patients received chemotherapy (Group C) and 41 patients received chemotherapy combined with radiotherapy (Group D). At half month postoperatively, the dysphagia remission rate in Group A (100%) was better than that in Groups B (39.3%), C (20%), D (15.8%), respectively, in the original cohort (P < 0.01); At 1 month postoperatively, the dysphagia remission rate in Group A (86.7%) was better than that in Group B (57.1%) (P > 0.05), Group C (25.7%) (P < 0.05) and Group D (34.2%) (P < 0.05), respectively, in the original cohort. There was no statistically significant difference in median overall survival (OS) between Group A (16 months) and Group B (37 months) (P = 0.149), and between Group A (16months) and Group C (16 months) (P = 0.918) in the original cohort. The mean OS of Group D (54 months) was better than that of Group A (20 months) in the original cohort (P = 0.031). The incidences of grade ≥2 myelosuppression in Groups B, C, and D were 12.9%, 28.9%, and 43.9%, respectively; the incidence of grade ≥2 gastrointestinal adverse events in Groups B, C, and D were 12.9%, 15.8%, 12.2%, respectively. No serious adverse events were found in Group A. The radiation dose around the patient was reduced to a safe range after the distance from the implantation site was more than 1 m (4.2 ± 2.6 µSv/h) or with lead clothing (0.1 ± 0.07 µSv/h). CONCLUSIONS: Compared with conventional radiotherapy or chemotherapy alone, iodine-125 seed implantation might improve dysphagia more quickly and safely, further clinical data is needed to verify whether it could effectively prolong the OS of patients.

BgNet: Classification of benign and malignant tumors with MRI multi-plane attention learning.

Objectives: To propose a deep learning-based classification framework, which can carry out patient-level benign and malignant tumors classification according to the patient's multi-plane images and clinical information. Methods: A total of 430 cases of spinal tumor, including axial and sagittal plane images by MRI, of which 297 cases for training (14072 images), and 133 cases for testing (6161 images) were included. Based on the bipartite graph and attention learning, this study proposed a multi-plane attention learning framework, BgNet, for benign and malignant tumor diagnosis. In a bipartite graph structure, the tumor area in each plane is used as the vertex of the graph, and the matching between different planes is used as the edge of the graph. The tumor areas from different plane images are spliced at the input layer. And based on the convolutional neural network ResNet and visual attention learning model Swin-Transformer, this study proposed a feature fusion model named ResNetST for combining both global and local information to extract the correlation features of multiple planes. The proposed BgNet consists of five modules including a multi-plane fusion module based on the bipartite graph, input layer fusion module, feature layer fusion module, decision layer fusion module, and output module. These modules are respectively used for multi-level fusion of patient multi-plane image data to realize the comprehensive diagnosis of benign and malignant tumors at the patient level. Results: The accuracy (ACC: 79.7%) of the proposed BgNet with multi-plane was higher than that with a single plane, and higher than or equal to the four doctors' ACC (D1: 70.7%, p=0.219; D2: 54.1%, p<0.005; D3: 79.7%, p=0.006; D4: 72.9%, p=0.178). Moreover, the diagnostic accuracy and speed of doctors can be further improved with the aid of BgNet, the ACC of D1, D2, D3, and D4 improved by 4.5%, 21.8%, 0.8%, and 3.8%, respectively. Conclusions: The proposed deep learning framework BgNet can classify benign and malignant tumors effectively, and can help doctors improve their diagnostic efficiency and accuracy. The code is available at https://github.com/research-med/BgNet.

Phytochemical and pharmacological studies on Solanum lyratum: a review.

Solanum lyratum is one of the temperate plants, broadly distributed in Korea, China, Japan, India, and South-East Asia and well-documented in those oriental ethnic medicine systems for curing cancers, jaundice, edema, gonorrhea, cholecystitis, phlogosis, rheumatoid arthritis, etc. This review systematically summarized the research progress on S. lyratum respecting the botany, traditional uses, phytochemistry, pharmacology, and toxicology to increase people's in-depth understanding of this plant, by data retrieval in a series of online or off-line electronic databases as far as we can reach. Steroidal saponins and alkaloids, terpenoids, nitrogenous compounds, and flavonoid compounds are the main chemical constituents in S. lyratum. Among them, steroidal alkaloids and saponins are the major active ingredients ever found in S. lyratum, exerting activities of anti-cancer, anti-inflammation, anti-microbial, anti-allergy, and anti-oxidation in vivo or in vitro. As a result, S. lyratum has been frequently prescribed for the abovementioned therapeutic purposes, and there are substantial traditional and modern shreds of evidence of its use.

Analysis of risk factors for post-endoscopic papillectomy bleeding.

BACKGROUND: Endoscopic papillectomy (EP) is an effective treatment for ampullary lesions but technically challenging because of anatomical specificities concerning the high rate of adverse events. Bleeding is one of the most feared complications and can be potentially life-threatening. AIM: To study the risk factors for bleeding after EP are presented with the goal of establishing preventive measures. METHODS: A total of 173 consecutive patients with ampullary lesions undergone EP from January 2006 to October 2020 were enrolled in this study. They were divided into a bleeding group and a non-bleeding group depending on whether postoperative bleeding occurred. Related factors were analyzed by univariate and multivariate logistics regression. RESULTS: Postoperative bleeding was experienced in 33 patients (19.07%). Multivariate analysis also identified intraoperative bleeding (OR: 4.38, 95% CI: 1.87-11.15, p = .001) and endoscopic closure (OR: 0.25, 95% CI: 0.10-0.58, p = .001) as independent factors significantly associated with bleeding after EP. Lesion size (≥3 cm) was shown as an independent factor significantly associated with intraoperative bleeding (OR: 4.25, 95% CI: 1.21-16.44, p = .028). CONCLUSIONS: This retrospective evaluation found that endoscopic closure was associated with reduced risk and intraoperative bleeding with increased risk of bleeding after EP. Lesion size may indirectly influence the risk of postoperative bleeding by increasing the risk of intraoperative bleeding.