Long-term outcomes of radiofrequency ablation for intrathoracic goiter up to 5 years: evaluated by computed tomography/magnetic resonance imaging and ultrasound.

OBJECTIVES: This study evaluated the long-term efficacy and safety of radiofrequency ablation (RFA) for intrathoracic goiter (ITG) over a follow-up period exceeding six months. METHODS: From 2017 to 2022, 22 patients (6 males, 16 females) with 24 ITGs treated with RFA at a single medical center were evaluated. All patients underwent ultrasonography (US), computed tomography (CT), or magnetic resonance imaging (MRI) before RFA. Follow-up CT/MRI was performed six months after the initial RFA and then every 6-12 months. The primary outcomes measured were the degree of extension, goiter volume, volume reduction rate (VRR), tracheal deviation, and tracheal lumen. Additionally, we assessed the outcomes of single-session RFA (n = 16) vs. multiple sessions (n = 8) on goiters and explored the correlation between ITG volume measurements obtained using ultrasonography and CT/MRI. RESULTS: The median follow-up period was 12 months (interquartile range: 6-36.8 months). At the last follow-up, the nodule volume measured by CT/MRI had significantly decreased (76.2 vs. 24.6 mL; p < 0.05), with a VRR of 64.6%. Patients who underwent multiple RFA sessions showed a significantly higher VRR than the single-session patients (63.8 vs. 80.1%, p < 0.05). The intraclass correlation between goiter volumes measured using US and CT/MRI was moderate. CONCLUSION: This study affirms the long-term efficacy and safety of RFA for ITG, providing an alternative treatment for nonsurgical candidates. Multiple RFA sessions may be beneficial for achieving better volume reduction. Sole reliance on ultrasonography is inadequate; therefore, integrating CT/MRI is essential for accurate pre-RFA and follow-up assessments.

Intrathoracic goiters significantly impact both cosmetic appearance and induce numerous compressive symptoms.Radiofrequency ablation brought notable volume reduction and persistent, effective alleviation of compressive symptoms.Radiofrequency ablation presents a promising therapeutic modality with long-term benefits for patients with intrathoracic goiter.

IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.

The mechanism by which interferon regulatory factor 8 (IRF8) mutation contributes to lymphomagenesis is unknown. We modeled IRF8 variants in B cell lymphomas and found that they affected the expression of regulators of antigen presentation. Expression of IRF8 mutants in murine B cell lymphomas suppressed CD4, but not CD8, activation elicited by antigen presentation and downmodulated CD74 and human leukocyte antigen (HLA) DM, intracellular regulators of antigen peptide processing/loading in the major histocompatibility complex (MHC) II. Concordantly, mutant IRF8 bound less efficiently to the promoters of these genes. Mice harboring IRF8 mutant lymphomas displayed higher tumor burden and remodeling of the tumor microenvironment, typified by depletion of CD4, CD8, and natural killer cells, increase in regulatory T cells and T follicular helper cells. Deconvolution of bulk RNA sequencing data from IRF8-mutant human diffuse large B cell lymphoma (DLBCL) recapitulated part of the immune remodeling detected in mice. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.

First report of Lasiodipilodia theobromae Causing leaf spot of Agave sisalana in GuangXi, China.

Agave sisalana, as an excellent fiber producing plant, is mainly planted in Guangxi Province, China. In November 2023, a foliar disease occured on A. sisalana at Liangjiang Town (108.3593 W, 23.4723 N), Wuming District, Nanning in GuangXi, China. Approximately 50 to 60% of the plants (n=200) had obvious leaf spots on more than 70% of the leaves. On the leaves of sisal, circular or irregularly shaped yellow brown spots can be seen, sunken, with no halo on the edges. As time goes on, the lesion gradually expands to the entire blade of the sword (Figure 1A, 1B). To identify the disease etiology, ten agave leaves were collected from GuangXi. Symptomatic midribs were cut into 3×3 mm pieces, surface sterilized with 75 % ethanol for 20 s, rinsed with sterilized distilled water three times, air dried on sterile filter paper, plated on photo dextrose agar (PDA) medium, and incubated at 28 ℃ in the dark. Five isolates (JM01, JM02, JM03, JM05, JM06) with similar morphology were obtained. Colonies on PDA medium were white to grayish-white with atrial mycelia growing initially upward and then forming clusters (Figure 1E). After five days, mycelia turned grayish black. Immature conidia were initially hyaline, aseptate, and ellipsoid. Mature conidia were dark brown, one septate, longitudinal striate, and 22.1 to 26.3×10.2 to 14.9 µm (Figure 1F). Morphologically , the isolates were identified as Lasiodiplodia theobromae (Alves et al. 2008). For molecular identification, genome DNA of five representative isolate was extracted using the Fungi Genomic DNA Purification kit. The internal transcribed spacer (ITS) region of rDNA and translation elongation factor 1-alpha (TEF-1α) and ß-tublin (TUB) gene were amplified with primer pairs ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), and Bt2a/Bt2b (Glass and Donaldson 1995), respectively, and sequenced. The ITS (PP209594), TEF-1α (PP234629), and TUB (PP234628) sequences of representative isolate JM01 were deposited in GeneBank. BLAST searches showed >99% nucleotide identity to sequences of L. theobromae (ITS, 99.26% to NR111174; TEF-1α, 99.69% to MM840490; TUB, 98.92% to MN172230). Phylogenetic analysis using maximum likelihood based on the combined ITS, TEF-1α, and TUB sequences of the isolates and reference sequences of Lasiodiplodias spp. from GenBank indicated the isolates obtained in this study formed a clade strongly supported based on bootstrap values to the ex-type isolate CBS164.96 sequences of L.theobromae (Figure 2). To test pathogenicity, JM01 was tested by inoculation leaves of one year old agave plants, the epidermis at the inoculation site, 10, 15 and 20 cm below to the crown, was wiped with a 75% alcohol cotton ball, washed three times with sterile water, and punctured (5 mm diameter) with a sterile inoculation needle. A 5 mm block of each isolate cultured on PDA for 3 days was attached to the inoculation site. Controls were inoculated with sterile PDA. The inoculation area was covered with plastic wrap. All plants were kept in a controlled greenhouse at 27℃, 80% relative humidity, and natural daylight, and watered weekly. Each treatment was repeated three times. Remove the block one day later. Three days after inoculation, all inoculated had typical symptoms,but control were healthy (Figure 1C, 1D). Fungal isolates were only recovered from symptomatic stems and were morphologically identical to L. theobromae, completing Koch's postulates. L. Theobromae has been reported as the cause of leaf rot on A. angustifolia in Mexico (Reyes-García et al. 2023). To our knowledge, this is the first report of L. theobromae causing leaf spot on A. sisalana in GuangXi, China. L. theobromae is primarily a plant pathogen that causes rotting and dieback in fruits and plants in tropical and subtropical regions (Puttanna 1967). This study is useful to focus on management strategies for leaf rot disease by L. theobromae of A. sisalana.

Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial.

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer; however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. Senaparib is a PARP inhibitor that demonstrated antitumor activity in patients with solid tumors, including ovarian cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally once daily for up to 2 years. The primary endpoint was progression-free survival assessed by blinded independent central review. At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32-0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively. Senaparib significantly improved progression-free survival versus placebo in patients with advanced ovarian cancer after response to first-line platinum-based chemotherapy, irrespective of BRCA1 and BRCA2 mutation status and with consistent benefits observed between homologous recombination subgroups, and was well tolerated. These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .

Identifying vagal bronchopulmonary afferents mediating cough response to inhaled sulfur dioxide in mice.

Sulfur dioxide (SO2), a common environmental and industrial air pollutant, possesses a potent effect in eliciting cough reflex, but the primary type of airway sensory receptors involved in its tussive action has not been clearly identified. This study was carried out to determine the relative roles of three major types of vagal bronchopulmonary afferents [slowly adapting receptors (SARs), rapidly adapting receptors (RARs), and C-fibers] in regulating the cough response to inhaled SO2. Our results showed that inhalation of SO2 (300 or 600 ppm for 8 min) evoked an abrupt and intense stimulatory effect on bronchopulmonary C-fibers, which continued for the entire duration of inhalation challenge and returned toward the baseline in 1-2 min after resuming room air-breathing in anesthetized and mechanically ventilated mice. In stark contrast, the same SO2 inhalation challenge generated a distinct and consistent inhibitory effect on both SARs and phasic RARs; their phasic discharges synchronized with respiratory cycles during the baseline (breathing room air) began to decline progressively within 1-3 min after the onset of SO2 inhalation, ceased completely before termination of the 8-min inhalation challenge, and then slowly returned toward the baseline after >40 min. In a parallel study in awake mice, inhalation of SO2 at the same concentration and duration as that in the nerve recording experiments evoked cough responses in a pattern and time course similar to that observed in the C-fiber responses. Based on these results, we concluded that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough response to inhaled SO2.NEW & NOTEWORTHY This study demonstrated that inhalation of a high concentration of sulfur dioxide, an irritant gas and common air pollutant, completely and reversibly inhibited the neural activities of both slowly adapting receptor and rapidly adapting receptor, two major types of mechanoreceptors in the lungs with their activities conducted by myelinated fibers. Furthermore, the results of this study suggested that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough reflex responses to inhaled sulfur dioxide.

Evaluation of retinal and choroidal thickness changes in overweight and obese adults without ocular symptoms by swept-source optical coherence tomography.

AIM: To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography (SS-OCT). METHODS: According to the body mass index (BMI) results, the adults enrolled in the cross-sectional study were divided into the normal group (18.50≤BMI<25.00 kg/m2), the overweight group (25.00≤BMI<30.00 kg/m2), and the obesity group (BMI≥30.00 kg/m2). The one-way ANOVA and the Chi-square test were used for comparisons. Pearson's correlation analysis was used to evaluate the relationships between the measured variables. RESULTS: This research covered the left eyes of 3 groups of 434 age- and sex-matched subjects each: normal, overweight, and obesity. The mean BMI was 22.20±1.67, 26.82±1.38, and 32.21±2.35 kg/m2 in normal, overweight and obesity groups, respectively. The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group (P<0.05 for all), while the retinal thickness of the three groups did not differ significantly. Pearson's correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness, but no significant correlation was observed between BMI and retinal thickness. CONCLUSION: Choroidal thickness is decreased in people with overweight or obesity. Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.

Rice receptor kinase FLR7 regulates rhizosphere oxygen levels and enriches the dominant Anaeromyxobacter that improves submergence tolerance in rice.

Oxygen is one of the determinants of root microbiome formation. However, whether plants regulate rhizosphere oxygen levels to affect microbiota composition and the underlying molecular mechanisms remain elusive. The receptor-like kinase (RLK) family member FERONIA modulates the growth-defense tradeoff in Arabidopsis. Here, we established that rice FERONIA-like RLK 7 (FLR7) controls rhizosphere oxygen levels by methylene blue staining, oxygen flux, and potential measurements. The formation of oxygen-transporting aerenchyma in roots is negatively regulated by FLR7. We further characterized the root microbiota of 11 FLR mutants including flr7 and wild-type Nipponbare (Nip) grown in the field by 16S ribosomal RNA gene profiling and demonstrated that the 11 FLRs are involved in regulating rice root microbiome formation. The most abundant anaerobic-dependent genus Anaeromyxobacter in the Nip root microbiota was less abundant in the root microbiota of all these mutants, and this contributed the most to the community differences between most mutants and Nip. Metagenomic sequencing revealed that flr7 increases aerobic respiration and decreases anaerobic respiration in the root microbiome. Finally, we showed that a representative Anaeromyxobacter strain improved submergence tolerance in rice via FLR7. Collectively, our findings indicate that FLR7 mediates changes in rhizosphere oxygen levels and enriches the beneficial dominant genus Anaeromyxobacter and may provide insights for developing plant flood prevention strategies via the use of environment-specific functional soil microorganisms.

Fabrication of a ZIF-on-lamella-zeolite architecture as a highly efficient catalyst for aldol condensation.

Designing composite catalysts that harness the strengths of individual components while mitigating their limitations is a fascinating yet challenging task in catalyst engineering. In this study, we aimed to enhance the catalytic performance by anchoring ZIF-67 nanoparticles of precise sizes onto lamella Si-MWW zeolite surfaces through a stepwise regrowth process. Co ions were initially grafted onto the zeolite surface using ultrasonication, followed by a seed-assisted secondary growth method. Si-MWW proved to be the ideal zeolite support due to its thin layered structure, large external surface area and substantial lateral dimensions. The abundant Si-OH groups on its surface played a crucial role in securely binding Co ions, limiting size growth and preventing undesirable ZIF-67 aggregation. The resulting ZIF-67/MWW composite with finely dispersed nano-scale ZIF-67 particles exhibited a remarkable catalytic performance and stability in the aldol condensation reactions involving acetone and various aldehydes. This approach holds promise for designing MOF/zeolite composite catalysts.

Mild and Efficient Preparation of N-Heterocyclic Organic Molecules by Catalyst-free and Solvent-free Methods.

AIMS: The small organic molecular compounds with biological activity containing C-C and C-N or C-O bonding were efficiently prepared without catalyst and solvent in the hydrothermal synthesis reactor. OBJECTIVES: Our goal was to explore new applications for the more environmentally friendly and efficient synthesis of bis(indolyl)methyl, xanthene, quinazolinone, and N-heterocyclic derivatives in hydrothermal synthesis reactors under solvent-free and catalyst-free conditions. METHODS: A greener and more efficient method was successfully developed for the synthesis of bis(indolyl)methyl, heteroanthracene, quinazolinone, and N-heterocyclic derivatives using a hydrothermal synthesis reactor in a solvent- and catalyst-free manner. RESULTS: In a hydrothermal synthesis reactor, bis(indoyl)methyl, xanthene, quinazolinone, and N-heterocyclic derivatives were synthesized without catalysts and solvents. CONCLUSION: Overall, it is proved once again that the catalyst-free and solvent-free synthesis method has universal value and is a more ideal and environmentally friendly new method, especially the hydrothermal reactor for synthesis.

Natural product-derived ferroptosis mediators.

It has been 11 years since ferroptosis, a new mode of programmed cell death, was first proposed. Natural products are an important source of drug discovery. In the past five years, natural product-derived ferroptosis regulators have been discovered in an endless stream. Herein, 178 natural products discovered so far to trigger or resist ferroptosis are classified into 6 structural classes based on skeleton type, and the mechanisms of action that have been reported are elaborated upon. If pharmacodynamic data are sufficient, the structure and bioactivity relationship is also presented. This review will provide medicinal chemists with some effective ferroptosis regulators, which will promote the research of natural product-based treatment of ferroptosis-related diseases in the future.

The novel HLA-C*01:255 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*01:255 differs from HLA-C*01:02:01:01 by one nucleotide in exon 2.

Rare 7,9'-dinorlignans with neuroprotective activity from the roots of Lindera aggregata (Sims) Kosterm.

Linderagatins C-F (1-4), the first examples of naturally occurring diaryltetrahydrofuran-type 7,9'-dinorlignans, were characterized from the roots of Lindera aggregata (Sims) Kosterm. The structures of these dinorlignans were elucidated by extensive spectroscopic analysis. The absolute configurations were determined based on calculated and experimental ECD data. A biosynthetic pathway for these dinorlignans was hypothetically proposed. Compounds 2 and 3 showed significant neuroprotective effects on erastin-induced ferroptosis in HT-22 cells with EC50 values of 23.4 and 21.8 µM, respectively.

Acid protonation promoted different crystal phase structure silicon carbide-based carbon nitride composites to enhance the photocatalytic degradation of dye wastewater.

Acid-protonated crystalline silicon carbide-supported carbon nitride photocatalytic composites were successfully prepared by the impregnation-heat treatment method (P-g-C3N4/ß-SiC and P-g-C3N4/α-SiC). The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), UV-vis diffuse reflectance spectra (UV-vis-DRS) photoluminescence (PL), etc. The results of SEM showed that the P-g-C3N4/ß-SiC and P-g-C3N4/α-SiC materials were transformed from large-area lamellar structures to uniform and dispersed lamellar particles. The UV-vis-DRS and PL showed that the recombination probability of photogenerated electron-hole pairs of P-g-C3N4/ß-SiC and P-g-C3N4/α-SiC samples decreased and the band gap increased. The results of photocatalytic degradation of alizarin red S (ARS), acid fuchsin (AF), and basic fuchsin (BF) showed that the samples P-g-C3N4/ß-SiC and P-g-C3N4/α-SiC had excellent photocatalytic degradation performance. It is worth noting that the degradation performance of the sample P-g-C3N4/ß-SiC on the three dyes is better than that of P-g-C3N4/α-SiC. The electron spin resonance spectra (ESR) results showed that the ˙O2- and ˙OH produced by the two catalysts during the dye degradation process played a leading role in the degradation reaction. Fortunately, the catalyst maintains an excellent cycle life and can be reused more than seven times while degrading all three dyes.

Factors Influencing a Favorable Outcome for RFA of Huge Benign Thyroid Nodules: Preliminary Results and Short-Term Evaluation.

Objective: This study aimed to investigate potentially favorable factors influencing the therapeutic success of radiofrequency ablation (RFA) of huge benign thyroid nodules (BTNs) (volume >100 ml) and to evaluate the feasibility of RFA as an alternative treatment modality for patients unable or unwilling to undergo surgery. Methods: This retrospective study evaluated a total of 868 patients, of which 22 patients had huge BTNs who underwent ultrasound-guided moving shot RFA treatment between May 2017 and January 2022. The huge BTNs were categorized into two groups according to a post-RFA treatment volume reduction ratio (VRR) of >80% and <80% at 6 months. Factors influencing these huge BTNs were reviewed, analyzed, and correlated with treatment effectiveness between the two groups. Results: The factors influencing an effective VRR included huge BTNs located on the left side (OR 7.875, p = 0.03), predominant solid/spongiform nodules (OR 7.875, p = 0.03), and higher initial ablation rate (IAR) (p = 0.028). Multivariable logistic regression revealed predominant solid/spongiform nodule and the higher IAR were associated with the advanced VRR. Conclusion: RFA was effective at decreasing the volume of huge BTNs with an acceptable complication rate. The BTN characteristics correlated with a better VRR at the 6-month short-term follow-up were predominant solid/spongiform BTNs and those with the first time ablation treatment initial ablation rate. Nevertheless, regarding the higher regrowth rate of these groups of patients who may need to be treated more times, RFA can only be a feasible alternative treatment modality for patients unable or unwilling to undergo operation.

Three-dimensional computed tomography reconstruction diagnosed digestive tract perforation and acute peritonitis caused by Monopterus albus: A case report.

BACKGROUND: Few reports have described living foreign bodies in the human body. The current manuscript demonstrates that computed tomography (CT) is an effective tool for accurate preoperative evaluation of living foreign bodies in clinic. The three-dimensional (3D) reconstruction technology could clearly display anatomical structures, lesions and adjacent organs, improving diagnostic accuracy and guiding the surgical decision-making process. CASE SUMMARY: Herein we describe a 68-year-old man diagnosed with digestive tract perforation and acute peritonitis caused by a foreign body of Monopterus albus. The patient presented to the emergency department with complaints of dull abdominal pain, profuse sweating and a pale complexion during work. A Monopterus albus had entered the patient's body through the anus two hours ago. During hospitalization, the 3D reconstruction technology revealed a perforation of the middle rectum complicated with acute peritonitis and showed a clear and complete Monopterus albus bone morphology in the abdominal and pelvic cavities, with the Monopterus albus biting the mesentery. Laparoscopic examination detected a large (diameter of about 1.5 cm) perforation in the mid-rectum. It could be seen that a Monopterus albus had completely entered the abdominal cavity and had tightly bitten the mesentery of the small intestine. During the operation, the dead Monopterus albus was taken out. CONCLUSION: The current manuscript demonstrates that CT is an effective tool for accurate preoperative evaluation of living foreign bodies in clinic.

IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHC CII complexes.

In diffuse large B-cell lymphoma (DLBCL), the transcription factor IRF8 is the target of a series of potentially oncogenic events, including, chromosomal translocation, focal amplification, and super-enhancer perturbations. IRF8 is also frequently mutant in DLBCL, but how these variants contribute to lymphomagenesis is unknown. We modeled IRF8 mutations in DLBCL and found that they did not meaningfully impact cell fitness. Instead, IRF8 mutants, mapping either to the DNA-binding domain (DBD) or c-terminal tail, displayed diminished transcription activity towards CIITA, a direct IRF8 target. In primary DLBCL, IRF8 mutations were mutually exclusive with mutations in genes involved in antigen presentation. Concordantly, expression of IRF8 mutants in murine B cell lymphomas uniformly suppressed CD4, but not CD8, activation elicited by antigen presentation. Unexpectedly, IRF8 mutation did not modify MHC CII expression on the cell surface, rather it downmodulated CD74 and HLA- DM, intracellular regulators of antigen peptide processing/loading in the MHC CII complex. These changes were functionally relevant as, in comparison to IRF8 WT, mice harboring IRF8 mutant lymphomas displayed a significantly higher tumor burden, in association with a substantial remodeling of the tumor microenvironment (TME), typified by depletion of CD4, CD8, Th1 and NK cells, and increase in T-regs and Tfh cells. Importantly, the clinical and immune phenotypes of IRF8-mutant lymphomas were rescued in vivo by ectopic expression of CD74. Deconvolution of bulk RNAseq data from primary human DLBCL recapitulated part of the immune remodeling detected in mice and pointed to depletion of dendritic cells as another feature of IRF8 mutant TME. We concluded that IRF8 mutations contribute to DLBCL biology by facilitating immune escape.

Nasopharyngeal carcinoma patient-derived xenograft mouse models reveal potential drugs targeting cell cycle, mTOR, and autophagy pathways.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening. METHODS: Based on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis. RESULTS: Everolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90). CONCLUSIONS: High mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs.

A prognostic model using FIGO 2018 staging and MRI-derived tumor volume to predict long-term outcomes in patients with uterine cervical squamous cell carcinoma who received definitive radiotherapy.

BACKGROUND: Uterine cervical carcinoma is a severe health threat worldwide, especially in China. The International Federation of Gynecology and Obstetrics (FIGO) has revised the staging system, emphasizing the strength of magnetic resonance imaging (MRI). We aimed to investigate long-term prognostic factors for FIGO 2018 stage II-IIIC2r uterine cervical squamous cell carcinoma following definitive radiotherapy and establish a prognostic model using MRI-derived tumor volume. METHODS: Patients were restaged according to the FIGO 2018 staging system and randomly grouped into training and validation cohorts (7:3 ratio). Optimal cutoff values of squamous cell carcinoma antigen (SCC-Ag) and tumor volume derived from MRI were generated for the training cohort. A nomogram was constructed based on overall survival (OS) predictors, which were selected using univariate and multivariate analyses. The performance of the nomogram was validated and compared with the FIGO 2018 staging system. Risk stratification cutoff points were generated, and survival curves of low-risk and high-risk groups were compared. RESULTS: We enrolled 396 patients (training set, 277; validation set, 119). The SCC-Ag and MRI-derived tumor volume cutoff values were 11.5 ng/mL and 28.85 cm3, respectively. A nomogram was established based on significant prognostic factors, including SCC-Ag, poor differentiation, tumor volume, chemotherapy, and FIGO 2018 stage. Decision curve analysis indicated that the net benefits of our model were higher. The high-risk group had significantly shorter OS than the low-risk group in both the training (p < 0.0001) and validation sets (p = 0.00055). CONCLUSIONS: Our nomogram predicted long-term outcomes of patients with FIGO 2018 stage II-IIIC2r uterine cervical squamous cell carcinoma. This tool can assist gynecologic oncologists and patients in treatment planning and prognosis.

Seed-Assisted Interzeolite Conversion Strategy for Fabricating Lewis Acid Sn-CHA Zeolites.

Small-pore Lewis acid zeolites have been showing increasing potential in shape-selective reactions regarding small-molecule conversion. In this study, Sn-CHA with tunable framework Sn contents was facilely prepared via a fluoride-free, seed-assisted interzeolite conversion (IZC) pathway. Commercially available dealuminated USY functioned as the parent sample, and seeding played a vital role in accelerating the transformation process, promoting the target zeolite yield, and guiding the attached-growth pathway. Notably, a proto-zeolite phase with a semi-constructed pore structure was captured during the IZC process, which represents a crucial intermediate stage for developing the complete CHA structure and ensuring a well-defined Sn status. The detailed synthesis mechanism was explored in multiscale by a series of techniques. The obtained Sn-CHA and proto-Sn-CHA exhibited excellent catalytic performance in converting 1,3-dihydroxyacetone to methyl lactate. Proto-Sn-CHA was proven to be a highly effective glucose isomerization catalyst owing to its larger pore size and Lewis acidic nature.

Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial.

Importance: The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease. Objective: To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted). Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months. Interventions: Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/µL [to convert to ×109/µL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. Main Outcomes and Measurements: The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population. Results: A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events. Conclusion and Relevance: This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting. Trial Registration: ClinicalTrials.gov Identifier: NCT03709316.