Ultrasound-Guided Sialendoscopy Surgery for Parotid Sialolithiasis Using Yttrium Aluminum Garnet (YAG)-Holmium Laser: A Prospective Case Series.

BACKGROUND: Parotid sialolithiasis is a common condition in middle-aged individuals, with most cases occurring in the submandibular and sublingual glands, followed by the parotid glands and minor salivary glands. The treatment of salivary gland stones, particularly those of the parotid glands, remains challenging. Endoscopic surgery using a yttrium aluminum garnet (YAG)-holmium laser for parotid sialolithiasis is a minimally invasive approach that provides effective treatment for patients. This study aimed to evaluate the outcomes of the endoscopic laser treatment of parotid sialolithiasis a YAG-holmium laser. MATERIALS AND METHODS: A prospective case series study was conducted on 21 patients diagnosed with salivary gland stones in the parotid gland based on clinical features and imaging findings (including ultrasound and computed tomography scans), from March 2022 to March 2024. These patients underwent sialendoscopy surgery using a YAG-holmium laser and were evaluated for surgical results at 2, 4, and 12 weeks. RESULTS: Cases with completely reduced symptoms accounted for 90.5%, whereas cases with partially reduced symptoms accounted for 9.5%. The ultrasound image of the salivary gland after surgery was significantly improved compared to that before surgery. After three months of surgery, most patients (90.5%) were satisfied. The postoperative complication rate was 14.3%, which included scarring at the opening of the salivary gland and in the salivary duct. CONCLUSION: Sialendoscopic surgery using a YAG-holmium laser for parotid sialolithiasis is a minimally invasive surgical intervention that leaves no scarring, reduces the risk of complications as seen in open surgery, and shortens the postoperative care time for patients.

Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella.

Synergistic combinations of immunotherapeutic agents can improve the performance of anti-cancer therapies but may lead to immune-mediated adverse effects. These side-effects can be overcome by using a tumor-specific delivery system. Here, we report a method of targeted immunotherapy using an attenuated Salmonella typhimurium (SAM-FC) engineered to release dual payloads: cytolysin A (ClyA), a cytolytic anti-cancer agent, and Vibrio vulnificus flagellin B (FlaB), a potent inducer of anti-tumor innate immunity. Localized secretion of ClyA from SAM-FC induces immunogenic cancer cell death and promotes release of tumor-specific antigens and damage-associated molecular patterns, which establish long-term antitumor memory. Localized secretion of FlaB promotes phenotypic and functional remodeling of intratumoral macrophages that markedly inhibits tumor metastasis in mice bearing tumors of mouse and human origin. Both primary and metastatic tumors from bacteria-treated female mice are characterized by massive infiltration of anti-tumorigenic innate immune cells and activated tumor-specific effector/memory T cells; however, the percentage of immunosuppressive cells is low. Here, we show that SAM-FC induces functional reprogramming of the tumor immune microenvironment by activating both the innate and adaptive arms of the immune system and can be used for targeted delivery of multiple immunotherapeutic payloads for the establishment of potent and long-lasting antitumor immunity.

Primary Nasopharyngeal Papillary Adenocarcinoma: Report of 2 Cases and Review of the Literature.

The primary nasopharyngeal papillary adenocarcinoma (NPPA) is extremely rare which accounts for less than 0.48% of all malignant neoplasms in the nasopharynx. The clinical features, diagnosis, and treatment of NPPA have not been well described. We present 2 patients with NPPA that were treated with total endoscopic resection and radiotherapy at Vietnam National Cancer Hospital. Through these cases and reviewing of the literature, we provide deeper understanding of NPPA to highlight clinical pathological characteristics and the optimal treatment strategy for patients with pathologically confirmed NPPA. Our 2 cases were successfully treated and remained disease-free 4 years after treatment. The NPPA was usually an indolent tumor with polypoid appearance and slow growth rate and has a good prognosis. Surgical excision, including endonasal endoscopic excision with or without adjuvant radiotherapy, was most effective with a localized and operable tumor.

Development and Characterization of Quercetin-Loaded Polymeric Liposomes with Gelatin-Poly(ethylene glycol)-Folic Acid Coating to Increase Their Long-Circulating and Anticancer Activity.

Liposomes as drug-delivery systems have been researched and applied in multiple scientific reports and introduced as patented products with interesting therapeutic properties. Despite various advantages, this drug carrier faces major difficulties in its innate stability, cancer cell specificity, and control over the release of hydrophobic drugs, particularly quercetin, a naturally derived drug that carries many desirable characteristics for anticancer treatment. To improve the effectiveness of liposomes to deliver quercetin by tackling and mitigating the mentioned hurdles, we developed a strategy to establish the ability to passively target cancerous cells, as well as to increase the bioavailability of loaded drugs by incorporating poly(ethylene glycol), gelatin, and folic acid moieties to modify the liposomal system's surface. This research developed a chemically synthesized gelatin, poly(ethylene glycol), and folic acid as a single polymer to coat drug-loaded liposome systems. Liposomes were coated with gelatin-poly(ethylene glycol)-folic acid by electrostatic interaction, characterized by their size, morphology, ζ potential, drug loading efficiency, infrared structures, differential scanning calorimetry spectra, and drug-releasing profiles, and then evaluated for their cytotoxicity to MCF-7 breast cancer cells, as well as cellular uptake, analyzed by confocal imaging to further elaborate on the in vitro behavior of the coated liposome. The results indicated an unusual change in size with increased coating materials, followed by increased colloidal stability, ζ potential, and improved cytotoxicity to cancer cells, as shown by the cellular viability test with MCF-7. Cellular uptake also confirmed these results, providing data for the effects of biopolymer coating, while confirming that folic acid can increase the uptake of liposome by cancer cells. In consideration of such results, the modified gelatin-poly(ethylene glycol)-folic acid-coated liposome can be a potential system in delivering the assigned anticancer compound. This modified biopolymer showed excellent properties as a coating material and should be considered for further practical applications in the future.

De Novo Discovery of Pseudo-Natural Prenylated Macrocyclic Peptide Ligands.

Prenylation of peptides is widely observed in the secondary metabolites of diverse organisms, granting peptides unique chemical properties distinct from proteinogenic amino acids. Discovery of prenylated peptide agents has largely relied on isolation or genome mining of naturally occurring molecules. To devise a platform technology for de novo discovery of artificial prenylated peptides targeting a protein of choice, here we have integrated the thioether-macrocyclic peptide (teMP) library construction/selection technology, so-called RaPID (Random nonstandard Peptides Integrated Discovery) system, with a Trp-C3-prenyltransferase KgpF involved in the biosynthesis of a prenylated natural product. This unique enzyme exhibited remarkably broad substrate tolerance, capable of modifying various Trp-containing teMPs to install a prenylated residue with tricyclic constrained structure. We constructed a vast library of prenylated teMPs and subjected it to in vitro selection against a phosphoglycerate mutase. This selection platform has led to the identification of a pseudo-natural prenylated teMP inhibiting the target enzyme with an IC50 of 30 nM. Importantly, the prenylation was essential for the inhibitory activity, enhanced serum stability, and cellular uptake of the peptide, highlighting the benefits of peptide prenylation. This work showcases the de novo discovery platform for pseudo-natural prenylated peptides, which is readily applicable to other drug targets.

Pembrolizumab-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis in a Vietnamese patient with nonsmall-cell lung cancer.

Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.

Selective Dorsal Rhizotomy for Spastic Cerebral Palsy: Report of 18 Cases Performed in the North of Vietnam.

OBJECTIVE: The purpose of this report is to describe a case series of children undergoing selective dorsal rhizotomy (SDR) for the treatment of spastic cerebral palsy in Vietnam. Also described is an international cooperation model to facilitate the development of a new, multidisciplinary team for the evaluation and treatment of these children. METHODS: Details of international collaboration are described, including in-person travel and virtual interactions. All cases of children younger than 18 years undergoing SDR for treatment of spastic cerebral palsy at a single center in Hanoi, Vietnam are described, including preoperative evaluation of spasticity and gait as well as results at 6 and 12 months. Results are summarized using descriptive statistics. RESULTS: Since the beginning of cooperation in training and transferring SDR techniques by experts from the United States, in the period from June 2016 to December 2022, 18 SDR surgeries were performed in Hanoi. Patients' ages ranged from 2 to 14 years; 13 were male and 5 were female. Overall, approximately 60% of nerve rootlets were cut. Modified Ashworth Scale scores at 6 and 12 months after surgery in the hip, knee, and ankle joints showed improvement from preoperative values. There were 2 recorded complications: intracranial hypotension causing subdural hemorrhage and a case of skin infection at the incision site. CONCLUSIONS: The ongoing international cooperation between Vietnamese and American physicians has helped improve the surgical treatment of spasticity in children with cerebral palsy in Hanoi, providing children with a surgical treatment option with successful outcomes.

Biosynthesis of Macrocyclic Peptides with C-Terminal ß-Amino-α-keto Acid Groups by Three Different Metalloenzymes.

Advances in genome sequencing and bioinformatics methods have identified a myriad of biosynthetic gene clusters (BGCs) encoding uncharacterized molecules. By mining genomes for BGCs containing a prevalent peptide-binding domain used for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), we uncovered a new compound class involving modifications installed by a cytochrome P450, a multinuclear iron-dependent non-heme oxidative enzyme (MNIO, formerly DUF692), a cobalamin- and radical S-adenosyl-l-methionine-dependent enzyme (B12-rSAM), and a methyltransferase. All enzymes were functionally expressed in Burkholderia sp. FERM BP-3421. Structural characterization demonstrated that the P450 enzyme catalyzed the formation of a biaryl C-C cross-link between two Tyr residues with the B12-rSAM generating ß-methyltyrosine. The MNIO transformed a C-terminal Asp residue into aminopyruvic acid, while the methyltransferase acted on the ß-carbon of this α-keto acid. Exciton-coupled circular dichroism spectroscopy and microcrystal electron diffraction (MicroED) were used to elucidate the stereochemical configuration of the atropisomer formed upon biaryl cross-linking. To the best of our knowledge, the MNIO featured in this pathway is the first to modify a residue other than Cys. This study underscores the utility of genome mining to isolate new macrocyclic RiPPs biosynthesized via previously undiscovered enzyme chemistry.

Kaempferide triggers apoptosis and paraptosis in pancreatic tumor cells by modulating the ROS production, SHP-1 expression, and the STAT3 pathway.

Pancreatic cancer is one of the deadliest diseases with a poor prognosis and a five-survival rate. The STAT3 pathway is hyperactivated which contributes to the sustained proliferative signals in pancreatic cancer cells. We have isolated kaempferide (KF), an O-methylated flavonol, from the green propolis of Mimosa tenuiflora and examined its effect on two forms of cell death namely, apoptosis and paraptosis. KF significantly increased the cleavage of caspase-3 and PARP. It also downmodulated the expression of Alix (an intracellular inhibitor of paraptosis) and increased the expression of CHOP and ATF4 (transcription factors that promote paraptosis) indicating that KF promotes apoptosis as well as paraptosis. KF also increased intracellular reactive oxygen species (ROS) suggesting the perturbance of the redox state. N-acetylcysteine reverted the apoptosis- and paraptosis-inducing effects of KF. Some ROS inducers are known to suppress the STAT3 pathway and investigation revealed that KF downmodulates STAT3 and its upstream kinases (JAK1, JAK2, and Src). Additionally, KF also elevated the expression of SHP-1, a tyrosine phosphatase which is involved in the negative modulation of the STAT3 pathway. Knockdown of SHP-1 prevented KF-driven STAT3 inhibition. Altogether, KF has been identified as a promoter of apoptosis and paraptosis in pancreatic cancer cells through the elevation of ROS generation and SHP-1 expression.

Tumor Pre-Targeting System Using Streptavidin-Expressing Bacteria.

PURPOSE: A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe. PROCEDURES: We constructed a plasmid expressing mSA fused to maltose-binding protein and optimized the ribosome binding site sequence to increase solubility and expression levels. E. coli MG1655 was transformed with the recombinant plasmid, expression of which is driven by the pBAD promotor. Expression of mSA was induced by L-arabinose 4 days after injection of bacteria into mice bearing CT26 mouse colon carcinoma cells. Selective accumulation of mSA in tumor tissues was visualized by optical imaging after administration of a biotinylated fluorescent dye. Counting of viable bacterial cells was also performed. RESULTS: Compared with a conventional system, the novel expression system resulted in significantly higher expression of mSA and sustained binding to biotin. Imaging signals in tumor tissues were significantly stronger in the mSA-expressing group than in non-expressing group (P = 0.0005). Furthermore, the fluorescent signal in tumor tissues became detectable again after multiple inductions with L-arabinose. The bacterial counts in tumor tissues showed no significant differences between conditions with and without L-arabinose (P = 0.45). Western blot analysis of tumor tissues confirmed expression and binding of mSA to biotin. CONCLUSIONS: We successfully engineered tumor-targeting bacteria carrying a recombinant plasmid expressing mSA, which was targeted to, and expressed in, tumor tissues. These data demonstrate the potential of this novel tumor pre-targeting system when combined with biotinylated imaging probes or therapeutic agents.

Correction to "Mannosylated STING Agonist Drugamers for Dendritic Cell-Mediated Cancer Immunotherapy".

[This corrects the article DOI: 10.1021/acscentsci.3c01310.].

Molybdenum oxide/nickel molybdenum oxide heterostructures hybridized active platinum co-catalyst toward superb-efficiency water splitting catalysis.

A new catalyst has been developed that utilizes molybdenum oxide (MoO3)/nickel molybdenum oxide (NiMoO4) heterostructured nanorods coupled with Pt ultrafine nanoparticles for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) toward industrial-grade water splitting. This catalyst has been synthesized using a versatile approach and has shown to perform better than noble-metals catalysts, such as Pt/C and RuO2, at industrial-grade current level (≥1000 mA·cm-2). When used simultaneously as a cathode and anode, the proposed material yields 10 mA·cm-2 at a remarkably small cell voltage of 1.55 V and has shown extraordinary durability for over 50 h. Density functional theory (DFT) calculations have proved that the combination of MoO3 and NiMoO4 creates a metallic heterostructure with outstanding charge transfer ability. The DFT calculations have also shown that the excellent chemical coupling effect between the MoO3/NiMoO4 and Pt synergistically optimize the charge transfer capability and Gibbs free energies of intermediate species, leading to remarkably speeding up the reaction kinetics of water electrolysis.

Mannosylated STING Agonist Drugamers for Dendritic Cell-Mediated Cancer Immunotherapy.

The Stimulator of Interferon Genes (STING) pathway is a promising target for cancer immunotherapy. Despite recent advances, therapies targeting the STING pathway are often limited by routes of administration, suboptimal STING activation, or off-target toxicity. Here, we report a dendritic cell (DC)-targeted polymeric prodrug platform (polySTING) that is designed to optimize intracellular delivery of a diamidobenzimidazole (diABZI) small-molecule STING agonist while minimizing off-target toxicity after parenteral administration. PolySTING incorporates mannose targeting ligands as a comonomer, which facilitates its uptake in CD206+/mannose receptor+ professional antigen-presenting cells (APCs) in the tumor microenvironment (TME). The STING agonist is conjugated through a cathepsin B-cleavable valine-alanine (VA) linker for selective intracellular drug release after receptor-mediated endocytosis. When administered intravenously in tumor-bearing mice, polySTING selectively targeted CD206+/mannose receptor+ APCs in the TME, resulting in increased cross-presenting CD8+ DCs, infiltrating CD8+ T cells in the TME as well as maturation across multiple DC subtypes in the tumor-draining lymph node (TDLN). Systemic administration of polySTING slowed tumor growth in a B16-F10 murine melanoma model as well as a 4T1 murine breast cancer model with an acceptable safety profile. Thus, we demonstrate that polySTING delivers STING agonists to professional APCs after systemic administration, generating efficacious DC-driven antitumor immunity with minimal side effects. This new polymeric prodrug platform may offer new opportunities for combining efficient targeted STING agonist delivery with other selective tumor therapeutic strategies.

Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry.

Hepatitis C virus (HCV) infection is tightly connected to the lipid metabolism with lipid droplets (LDs) serving as assembly sites for progeny virions. A previous LD proteome analysis identified annexin A3 (ANXA3) as an important HCV host factor that is enriched at LDs in infected cells and required for HCV morphogenesis. To further characterize ANXA3 function in HCV, we performed proximity labeling using ANXA3-BioID2 as bait in HCV-infected cells. Two of the top proteins identified proximal to ANXA3 during HCV infection were the La-related protein 1 (LARP1) and the ADP ribosylation factor-like protein 8B (ARL8B), both of which have been previously described to act in HCV particle production. In follow-up experiments, ARL8B functioned as a pro-viral HCV host factor without localizing to LDs and thus likely independent of ANXA3. In contrast, LARP1 interacts with HCV core protein in an RNA-dependent manner and is translocated to LDs by core protein. Knockdown of LARP1 decreased HCV spreading without altering HCV RNA replication or viral titers. Unexpectedly, entry of HCV particles and E1/E2-pseudotyped lentiviral particles was reduced by LARP1 depletion, whereas particle production was not altered. Using a recombinant vesicular stomatitis virus (VSV)ΔG entry assay, we showed that LARP1 depletion also decreased entry of VSV with VSV, MERS, and CHIKV glycoproteins. Therefore, our data expand the role of LARP1 as an HCV host factor that is most prominently involved in the early steps of infection, likely contributing to endocytosis of viral particles through the pleiotropic effect LARP1 has on the cellular translatome.

Morphological Characteristics of the Vietnamese Adult Human Acetabulum Using Multiplanar Reconstruction Computed Tomography in Total Hip Replacement Surgery.

Background: The anatomical parameters of the acetabulum vary among races and geographical regions. Multislice Computed Tomography (CT) has proven to be a practical approach to assess morphological parameters of the acetabulum. The purpose of this study was to explore morphological characteristics of the acetabulum measured by CT scans in Vietnamese adults. Methods: Thirty-five consecutive patients aged 18 years and older received indications and eligibility for total hip replacement surgery. Sixty-three acetabulum were examined with multislice computed tomographic system (CT) with multiplanar reconstruction (MPR). Measured morphometric parameters of acetabulum included acetabular inclination angle (AIA), acetabular anteversion angle (AAA), acetabular angle of sharp (AAS), sagittal acetabular angle (SAA), acetabular horizontal offset (AHO), transverse acetabular ligament anteversion (TALA), transverse acetabular ligament inclination (TALI), acetabular depth (ADe), acetabular depth ratio (ADr) and acetabular diameter (ADi). Results: The mean values of acetabular diameter, femoral head diameter, AIA, AAA, AAS, SAA, TALA, TALI, AHO, ADe, ADr were 50.22±3.56 mm, 43.54±3.68 mm, 40.27±5.09 mm, 13.30±5.54 mm, 39.46±5.41 mm, 26.38±9.01 mm, 9.49±3.92 mm, 47.70±6.73 mm, 3.06±0.37 mm, 18.62±2.95 mm and 309.60±41.87 mm. Conclusion: Our initial data has showed morphological characteristics of the acetabulum in Vietnamese adults, different from the populations from other parts of world. Also, significant correlation between the orientation of the acetabulum and the transverse acetabular ligament was documented.

Lymph node harvesting after laparoscopic complete mesocolic excision colectomy in colon cancer with practical application of glacial acid, absolute ethanol, water, and formaldehyde solution: A prospective cohort study.

Objectives: Quality of surgery has recently become an essential topic in the prognosis of colon cancer. Complete mesocolic excision for colon cancer has recently gained popularity with high-quality surgery. Patient specimens after complete mesocolic excision with central vessel ligation procedures have an integrity of the mesocolon and the yield of three fields of lymph node harvest. We apply the glacial acid, absolute ethanol, water, and formaldehyde solution to each specimen based on the Japanese classification of lymph node groups and station numbers. We aim to identify the distribution and status of lymph node metastasis according to each tumor site and some pathological characteristics related to this disease. Methods: A prospective cohort study was performed on 45 laparoscopic complete mesocolic excision surgery patients. Results: 2791 lymph nodes were harvested after complete mesocolic excision surgery. The average number was 62.0 ± 22.3 nodes. The mean tumor size (in the largest dimension) was 4.2 ± 1.8 cm. The average length of the resected bowel segments was 29.1 ± 7.7 cm. There are 63 (2.3%) node metastases in 2791 lymph nodes, in which 17/45 (37.8%) patients had pN(+). The minimum positive node size was 1 mm. The positive pericolic lymph nodes (station 1) accounted for the highest rate, with 53 nodes (1.9%). The number of lymph nodes in young age ⩽60 is more significant than in older. The results were similar, with a more significant node retrieval in the group with a tumor size >4.5 cm and specimen length >25 cm. The number of lymph nodes in lower tumor invasive (pT1,3) was smaller than pT4. Our research shows that the cecum, ascending, and descending colon had greater nodes than others, with a mean number of 78.6, 74.2, and 71.3, respectively. Conclusions: The metastasis and harvested lymph nodes accounted for the highest rate of colon cancer in station 1 and the lowest rate in station 3. The number of retrieved lymph nodes was significantly associated with tumor location, size, specimen length, and patient age.

Sulfonyl thiourea derivatives from 2-aminodiarylpyrimidines: In vitro and in silico evaluation as potential carbonic anhydrase I, II, IX, and XII inhibitors.

A series of synthesized sulfonyl thiourea derivatives (7a-o) of substituted 2-amino-4,6-diarylpyrimidines (4a-o) exhibited the remarkable inhibitory activity against some the human carbonic anhydrases (hCAs), including hCA I, II, IX, and XII isoforms. The inhibitory efficacy of synthesized sulfonyl thiourea derivatives were experimentally validated by in vitro enzymatic assays. 7a (KI = 46.14 nM), 7j (KI = 48.92 nM), and 7m (KI = 62.59 nM) (for isoform hCA I); 7f (KI = 42.72 nM), 7i (KI = 40.98 nM), and 7j (KI = 33.40 nM) (for isoform hCA II); 7j (KI = 228.5 nM), 7m (KI = 195.4 nM), and 7n (KI = 210.1 nM) (for isoform hCA IX); 7l (KI = 116.9 nM), 7m (KI = 118.8 nM), and 7n (KI = 147.2 nM) (for isoform hCA XII) in comparison with KI values of 452.1, 327.3, 437.2, and 338.9 nM, respectively, of the standard drug AAZ. These compounds also had significantly more potent inhibitory action against cytosolic isoform hCA I and tumor-associated isoforms hCA IX and hCA XII. Furthermore, the potential inhibitory compounds were subjected to in silico screening for molecular docking and molecular dynamics simulations. The results of in vitro and in silico studies revealed that compounds 7a, 7j, and 7m were the most promising derivatives in this series due to their significant effects on studied hCA I, II, IX, and XII isoforms, respectively. The results showed that the sulfonyl thiourea moiety was accommodated deeply in the active site and interacted with the zinc ion in the receptors.

Diagnostic algorithm for glioma grading using dynamic susceptibility contrast­enhanced magnetic resonance perfusion and proton magnetic resonance spectroscopy.

The present retrospective study aimed to investigate the diagnostic capacity of and design a diagnostic algorithm for dynamic susceptibility contrast-enhanced MRI (DSCE-MRI) and proton magnetic resonance spectroscopy (1H-MRS) in grading low-grade glioma (LGG) and high-grade glioma (HGG). This retrospective study enrolled 57 patients, of which 14 had LGG and 43 had HGG, five had World Health Organization grade 1, nine had grade 2, 20 had grade 3 and 23 had grade 4 glioma. All subjects underwent a standard 3T MRI brain tumor protocol with conventional MRI (cMRI) and advanced techniques, including DSCE-MRI and 1H-MRS. The associations of grade categorization with parameters in tumor and peritumor regions in the DSCE-MRI were examined, including tumor relative cerebral blood volume (TrCBV) and peripheral relative (Pr)CBV, as well as Tr and Pr cerebral blood flow (CBF) and 1H-MRS, including the creatine (Cr) and N-acetyl aspartate (NAA) ratios of choline (Cho), i.e. the TCho/NAA, PCho/NAA, TCho/Cr and PCho/Cr metabolite ratios. The data were compared using the Mann-Whitney U-test, independent samples t-test, Chi-square test, Fisher's exact test and receiver operating characteristic curve analyses. Decision tree analysis established an algorithm based on cutoffs for specified significant parameters. The PrCBF had the highest performance in the preoperative prediction of histological glioma grading, followed by the TrCBV, PrCBF, TrCBV, PCho/NAA, PCho/Cr, TCho/NAA and TCho/Cr. An algorithm based on TrCBV, PrCBF and TCho/Cr had a diagnostic accuracy of 100% for LGG and 90.7% for HGG and a misclassification risk of 7%. The cutoffs (sensitivity and specificity) were 2.48 (86 and 100%) for TrCBV, 1.26 (83.7 and 100%) for PrCBF and 3.18 (69.8 and 78.6%) for TCho/Cr. In conclusion, the diagnostic algorithm using TrCBV, PrCBF and TCho/Cr values, which were obtained from DSCE-MRI and 1H-MRS, increased diagnostic accuracy to 100% for LGGs and 90.7% for HGGs compared to previous studies using conventional MRI. This non-invasive advanced MRI diagnostic algorithm is recommended for clinical application for constructing preoperative strategies and prognosis of patients with glioma.

Apparent diffusion coefficient histogram in the differentiation of benign and malignant testicular tumors.

Purpose: This retrospective study assessed the value of histogram parameters of the apparent diffusion coefficient (ADC) map (HA) in differentiating between benign and malignant testicular tumors. We compared the diagnostic performance of two different volume-of-interest (VOI) placement methods: VOI 1, the entire tumor; VOI 2, the tumor excluding its cystic, calcified, hemorrhagic, and necrotic portions. Materials and methods: We retrospectively evaluated 45 patients with testicular tumors examined with scrotal contrast-enhanced magnetic resonance imaging. These patients underwent surgery with the pathological result of seven benign and 39 malignant tumors. We calculated the HA parameters, including mean, median, maximum, minimum, kurtosis, skewness, entropy, standard deviation (SD), mean of positive pixels, and uniformity of positive pixels by the two different VOI segmentation methods. We compared these parameters using the chi-square test, Mann-Whitney U test, and area under the receiver operating characteristic curve (AUC) to determine their optimal cut-off, sensitivity (Se), and specificity (Sp). Result: This study included 45 patients with 46 testicular lesions (seven benign and 39 malignant tumors), one of which had bilateral testicular seminoma. With the VOI 1 method, benign lesions had significantly lower maximum ADC (p = 0.002), ADC skewness (p = 0.017), and ADC variance (p = 0.000) than malignant lesions. In contrast, their minimum ADC was significantly higher ADC (p = 0.000). With the VOI 2 method, the benign lesions had significantly higher ADC SD (p = 0.048) and maximum ADC (p = 0.015) than malignant lesions. In contrast, their minimum ADC was significantly lower (p = 0.000). With the VOI 1 method, maximum ADC, ADC variance, and ADC skewness performed well in differentiating benign and malignant testicular lesions with cut-offs (Se, Sp, AUC) of 1846.000 (74.4%, 100%, 0.883), 39198.387 (79.5%, 85.7%, 0.868), and 0.893 (48.7%, 100%, 0.758). Conclusion: The HA parameters showed value in differentiating benign and malignant testicular neoplasms. The entire tumor VOI placement method was preferable to the VOI placement method excluding cystic, calcified, hemorrhagic, and necrotic portions in measuring HA parameters. Using this VOI segmentation, maximum ADC performed best in discriminating benign and malignant testicular lesions, followed by ADC variance and skewness.

Reprogramming a Doxycycline-Inducible Gene Switch System for Bacteria-Mediated Cancer Therapy.

PURPOSE: Attenuated Salmonella typhimurium is a potential biotherapeutic antitumor agent because it can colonize tumors and inhibit their growth. The present study aimed to develop a doxycycline (Doxy)-inducible gene switch system in attenuated S. typhimurium and assess its therapeutic efficacy in various tumor-bearing mice models. PROCEDURES: A Doxy-inducible gene switch system comprising two plasmids was engineered to trigger the expression of cargo genes (Rluc8 and clyA). Attenuated S. typhimurium carrying Rluc8 were injected intravenously into BALB/c mice bearing CT26 tumors, and bioluminescence images were captured at specified intervals post-administration of doxycycline. The tumor-suppressive effects of bacteria carrying clyA were evaluated in BALB/c mice bearing CT26 tumors and in C57BL/6 mice bearing MC38 tumors. RESULTS: Expression of the fimE gene, induced only in the presence of Doxy, triggered a unidirectional switch of the POXB20 promoter to induce expression of the cargo genes. The switch event was maintained over a long period of bacterial culture. After intravenous injection of transformed Salmonella into mice bearing CT26 tumors, the bacteria transformed with the Doxy-inducible gene switch system for Rluc8 targeted only tumor tissues and expressed the payloads 2 days after Doxy treatment. Notably, bacteria carrying the Doxy-inducible gene switch system for clyA effectively suppressed tumor growth and prolonged survival, even after just one Doxy induction. CONCLUSIONS: These results suggest that attenuated S. typhimurium carrying this novel gene switch system elicited significant therapeutic effects through a single induction triggering and were a potential biotherapeutic agent for tumor therapy.