A self-powered theranostic DNA nanodevice for amplification of both intracellular microRNA imaging and photodynamic therapy.

While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen (1O2) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O21 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors.

National investigation of bisphenols in the surface soil in China.

The long-term production and extensive use have resulted in the widespread presence of bisphenols (BPs) in the environment. In order to clarify the pollution characteristics and potential sources of BPs, the national scale surface soil samples were collected in China in 2019. The results demonstrated that 32 target BPs existed widely in soil with the highest concentration for bisphenol A (BPA), and at least 2 BPs were detected in each sample. The total concentration of Σ32BPs (from 0.387 to 713 ng/g) exhibited a stepwise decrease from southeastern coast to inland regions, and due to the presence of more pollution sources concentrations of Σ32BPs in urban areas were slightly higher than rural areas. The different industrial structures (such as plastics, epoxy resins, and thermal paper) may be the important factors for the different pollution levels between southeastern coast and other regions. In addition, the high organic matter content in soil and low temperature may be the reasons for high concentrations of Σ32BPs in Northeast China. The results of source identification using the Positive Matrix Factorization model indicated that BPs in soil were originated from three sources: old sources represented by BPA, relatively new sources characterized by bisphenol S, and sources from specific industries using bisphenol F. The estimated daily intake indicated that BPA exposure through soil accounted for only a small proportion of the total exposure compared to other exposure routes, and the risk by BPA in soil can be negligible to human health. In summary, the study provided basic pollution information of BPs in Chinese surface soil for future related studies.

Education attainment and nutritional status in the prevention of cognitive impairment in the hospitalized Chinese elderly.

BACKGROUND: Effect of education attainment and nutritional status on the development of cognitive impairment in Chinese elderly has not been reported. OBJECTIVE: To investigate the role of education and nutrition in preventing cognitive impairment in the hospitalized Chinese elderly. METHODS: Cognitive function was examined using the scoring system of Mini-Mental State Examination (MMSE) domains performed under instruction of Physicians of Geriatrics. Generalized linear mixed-effect regression was used for analyzing the association of demographic factors (age and gender), socioeconomic factors (education attainment and monthly income), as well as health-related factors (nutritional status, comorbidity, anxiety, and depression) and MMSE scores. RESULTS: Total 246 hospitalized Chinese elders were enrolled into this study. Of them, 96 participants were 60-70 years old, 65 participants were 71-80 years old, and 85 of them were 81 years or older. Of the examined factors, we found that age, education attainment, and nutritional status were significantly associated with the outcome of MMSE scores, while monthly income and health condition (comorbidity, anxiety, and depression) were not significantly associated with MMSE score. Furthermore, education attainment was significantly associated with majority of the MMSE domains, including orientation, registration, attention and calculation, recall, and most of language sub-domains. CONCLUSION: Education attainment and nutritional status were significantly associated with MMSE scores in the hospitalized Chinese elderly. Higher education and better nutritional status are protective factors for the development of cognitive impairment in the hospitalized elderly Chinese population.

Development of a rapid method for the simultaneous determination of aminophylline, doxofylline, bromhexine, and ambroxol by HPLC.

Introduction: Antitussive and expectorant drugs such as aminophylline (APL), doxofylline (DXL), bromhexine hydrochloride (BXH), and ambroxol hydrochloride (AXH), either individually or in combination, are widely used in the prevention and treatment of respiratory diseases. The study aimed to establish a high-performance liquid chromatography (HPLC) method for the simultaneous determination of these four drugs and to investigate their stability in 0.9% sodium chloride injection or 5% glucose injection over 48 hours. Methods: An InertSustain C18 column (150 mm × 4.6 mm, 5 µm) was used. The mobile phase consisted of acetonitrile and 50 mmol·L-1 potassium dihydrogen phosphate solution (pH 4.0) with gradient elution. The flow rate was 0.8 mL·min-1, and the column temperature was maintained at 30°C. The stability of APL, DXL, BXH, and AXH in 0.9% sodium chloride and 5% glucose injections over 48 h was determined using HPLC. Results: APL, DXL, BXH, and AXH showed good linearity within the ranges of 0.01 to 0.20, 0.003-0.06, 0.015-0.30, and 0.016-0.16 mg·mL-1, respectively (r > 0.999). The intraday and interday relative standard deviations were <2%, with recovery rates between 98.4% and 102.2%. The four drugs remained colorless and clear in infusion mixtures. The pH value fluctuated within ±0.3 over 48 hours, and the relative percentage content of the drugs ranged from 95.0% to 105.0%. Conclusion: The established HPLC method is simple, reliable, and stable, allowing for the simultaneous determination of the four antitussive and expectorant drugs. APL, DXL, BXH, and AXH were stable within 48 hours when mixed with 0.9% sodium chloride and 5% glucose injections.

Combination of pretarsal and preseptal botulinum toxin injections in the treatment of blepharospasm: A prospective nonrandomized clinical trial.

PURPOSE: To compare the efficacy of two botulinum toxin (BoNT) injection methods, pretarsal (PT) combined with preseptal (PS) injection (PT-PS) and conventional PT injection, in the treatment of benign essential blepharospasm (BEB). DESIGN: Prospective nonrandomized clinical trial. METHODS: From January 2023 to April 2024, 95 BoNT injections into orbicularis oculi were performed in 45 BEB patients, including 52 PT-PS injections s and 43 PT injections. Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI) were used to assess motor symptoms. The efficacy of two injection methods for BEB was compared in terms of latency to response (LTR), latency to the peak response (LPR), duration of peak response (DPR), duration of response (DOR), satisfaction degree, and possible complications. RESULTS: Both injection methods significantly improved JRS and BSDI scores in patients with BEB. However, PT-PS injections showed a shorter LTR [(4.00(3.00,6.00) vs 5.00(4.00,7.00) days, p=0.024] and LPR [23.50(16.00,26.00) vs 26.00(20.00,30.00) days, p=0.040], a longer DPR [88.00(80.50,104.75) vs 75.00(65.00,92.00) days, p=0.003] and DOR [135.00(118.50,153.75) vs 121.00(107.00,135.00) days, p=0.003] than PT injections. Patients with PT-PS injections were more satisfied than those with PT injections [9.50(8.50,10.00) vs 8.00(7.50,9.00), p<0.001], and around 2/3 of patients were more willing to receive the combined injection method later. Among patients receiving PT-PS injections, only one case experienced ptosis, and there were no significant differences in other complications such as lacrimation, dry eyes, and blurred vision between the two injection methods. CONCLUSIONS: PT-PS injections of BoNT showed more advantages in the treatment of BEB than PT injections in terms of both their efficacy and patients' satisfactions.

The clinical spectrum and pathogenesis associated with KMT2B variants in Chinese pediatric patients.

OBJECTIVE: To evaluate the clinical spectrum and pathogenesis associated with KMT2B variants in Chinese children with dystonia or developmental delay. METHODS: We reported twenty-seven (fourteen males and thirteen females) pediatric patients with KMT2B variants identified via next-generation sequencing from a single Chinese center. Moreover, transcriptomics and proteomics assays were performed on fibroblasts from patients with different genotypes to investigate the pathogenic mechanisms involved. RESULTS: Twenty-six patients had dystonia including generalized dystonia (n = 19), multifocal dystonia (n = 6), and segmental dystonia (n = 1), and one patient had nondystonic severe-developmental delay (DD). All the twenty-six patients had complex dystonia compounded with other manifestations of movement disorders (tremor (n = 6), myoclonus (n = 5), status dystonicus (n = 2), and tic (n = 1)) or dysmorphic features and developmental delay. The onset of dystonia was between 1 month and 13 years 8 months (median 4 years 4 months). Dystonia was aggravated by fever (n = 11), and diurnal and climate fluctuations (n = 4). Eleven patients underwent deep brain stimulation and experienced significant improvements in motor function and disability. We identified twenty-six intragenic heterozygous KMT2B pathogenic variants and one Chr:19q13.12 contiguous gene deletion. Sixteen variants were novel. Differentially expressed genes induced by KMT2B variants were significantly enriched for mitochondria-related biological processes in patient fibroblasts. As a result, mitochondrial morphology of mitochondria was altered, and aerobic respiration was impaired. CONCLUSION: Our study reports the pediatric cases of KMT2B-related disorder from a single center in China. Additionally, our study highlights the role of KMT2B variants in mitochondrial dysfunction.

Machine Learning-Based Detection of Bladder Cancer by Urine cfDNA Fragmentation Hotspots that Capture Cancer-Associated Molecular Features.

BACKGROUND: cfDNA fragmentomics-based liquid biopsy is a potential option for noninvasive bladder cancer (BLCA) detection that remains an unmet clinical need. METHODS: We assessed the diagnostic performance of cfDNA hotspot-driven machine-learning models in a cohort of 55 BLCA patients, 51 subjects with benign conditions, and 11 healthy volunteers. We further performed functional bioinformatics analysis for biological understanding and interpretation of the tool's diagnostic capability. RESULTS: Urinary cfDNA hotspots-based machine-learning model enabled effective BLCA detection, achieving high performance (area under curve 0.96) and an 87% sensitivity at 100% specificity. It outperformed models using other cfDNA-derived features. In stage-stratified analysis, the sensitivity at 100% specificity of the urine hotspots-based model was 71% and 92% for early (low-grade Ta and T1) and advanced (high-grade T1 and muscle-invasive) disease, respectively. Biologically, cfDNA hotspots effectively retrieved regulatory elements and were correlated with the cell of origin. Urine cfDNA hotspots specifically captured BLCA-related molecular features, including key functional pathways, chromosome loci associated with BLCA risk as identified in genome-wide association studies, or presenting frequent somatic alterations in BLCA tumors, and the transcription factor regulatory landscape. CONCLUSIONS: Our findings support the applicability of urine cfDNA fragmentation hotspots for noninvasive BLCA diagnosis, as well as for future translational study regarding its molecular pathology and heterogeneity.

Endonuclease G is dispensable for sperm mitochondrial DNA elimination during spermatogenesis in mice.

Maternal inheritance of mitochondrial DNA (mtDNA) is a widespread phenomenon in eukaryotes. Our earlier research indicated that sperm mtDNA is removed prior to fertilization in mice, and Endonuclease G (ENDOG) orchestrates the degradation of sperm mitochondria in Caenorhabditis elegans. However, the mechanisms underlying sperm mtDNA disposal in mammals remain poorly understood. To investigate the potential role of ENDOG in sperm mtDNA elimination, we created Endog knockout (Endog-/-) mice. Our findings revealed that Endog-/- mice maintained normal spermatogenesis and fertility. Most strikingly, we detected no substantial discrepancy in sperm mtDNA copy number between Endog-/- and control mice. Furthermore, we noted that sperm mtDNA copy numbers were unchanged in both less motile and motile sperm isolated by Percoll gradient centrifugation from Endog-/- and control mice. Taken together, our results indicate that ENDOG is not essential for spermatogenesis or the elimination of sperm mtDNA in mice.

Pathogen detection by targeted next-generation sequencing test in adult hematological malignancies patients with suspected infections.

Background: Infections in patients with hematological malignancies (HM) are a significant cause of morbidity and mortality. Timely and effective empirical anti-infective treatment can reduce the infection-related mortality rate. Targeted next-generation sequencing (tNGS) offers a rapid diagnostic approach for identifying diverse pathogens in these patients. However, relevant research is still limited to adult patients with HM. Methods: We conducted a retrospective analysis of adult HM patients admitted to our hospital from March 2023 to September 2023, focusing on their clinical characteristics and the results of both tNGS and conventional microbiological tests (CMTs). We evaluated the performance of tNGS and CMTs in pathogenic diagnosis and described the distribution characteristics of pathogens in adult HM patients with infections. Results: The study included 209 samples collected from 137 patients. Results showed that the overall pathogen detection rate differed significantly between tNGS and CMTs (60.3% vs. 24.4%, p < 0.001). The sensitivity (69.7% vs. 35.9%), negative predictive value (NPV) (48.2% vs. 42.4%), and accuracy (66.5% vs. 56.5%) of pathogen detection were notably superior with tNGS compared to CMTs. Among the 142 samples with clinically diagnosed infections, tNGS combined with CMTs identified a definite or probable microbial etiology in 114 samples (80.3%). Of the 36 samples with concordant positive results from both tNGS and CMTs, 72.2% (26/36) exhibited full or partial agreement. Our study further showed the highest detection rate for viral infections (57.0%), predominantly for Epstein-Barr virus (DNA-V, 18.3%). Followed by bacterial infections (46.5%), the detection rate of Gram-negative bacteria (G+, 35.9%) was higher than that of Gram-positive bacteria (G-, 21.8%) in this study. Klebsiella pneumoniae (G-, 12.7%) had the highest detection rate among these emerging bacteria, followed by Pseudomonas aeruginosa (G-, 10.6%) and Enterococcus faecium (G+, 7.7%). Bacterial-viral coinfections were the most common type of mixed infection (35.5%). Conclusion: In conclusion, tNGS outperforms CMTs in both sensitivity and pathogen spectrum. Therefore, it can serve as an adjunct to CMTs to facilitate the precise adjustment of anti-infective regimens for adult HM patients. Our findings establish a basis for formulating empirical anti-infective therapy strategies tailored to the pathogen distribution in this patient population.

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma - An Observational Study from Taiwan.

Background: Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear. Methods: In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns. Results: One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses. Conclusion: Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.

AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation.

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Anti-NMDAR encephalitis with delayed ovarian teratoma in a young woman: a case report with 5 years of follow-up.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder with a variety of clinical manifestations. It has been established that anti-NMDAR encephalitis may be related to ovarian teratoma in female patients. However, a considerable number of patients have no obvious evidence of ovarian teratoma during the onset of the disease. CASE: A 25-year-old previously-healthy female experienced a series of acute symptoms within two days, including confusion, disorientation, short-term memory loss, auditory hallucinations, abnormal behavior, refractory status epilepticus, etc. Her brain MRI and abdominal imaging showed no definite abnormality while her electroencephalogram exhibited the presence of low to moderate amplitude sharp, spike, and multi-spike waves. Serum and cerebrospinal fluid tests yielded positive results for anti-NMDAR antibodies. However, an ultrasound scan failed to identify an ovarian teratoma. Consequently, the diagnosis of anti-NMDAR encephalitis without teratoma was made after 4 days onset. After the plasma exchange and immunoglobulin therapy, her neurological symptoms improved and obtained a clinical cure. In the next eight months of follow-up, the patient accidentally touched a lump in the lower abdomen without any symptoms, and abdominal ultrasound and CT scan revealed a left ovarian tumor. Then she underwent left ovarian teratoma resection surgery and histopathology showed a mature cystic teratoma with neural components. The patient continued to receive five years of follow-up, and her condition remained stable without any recurrence, except that there had been a low titer of anti-NMDAR antibody in her serum. CONCLUSION: Our case demonstrated the importance of long-term follow-up for female patients with anti-NMDAR encephalitis, since anti-NMDAR encephalitis-associated ovarian teratomas may develop in a delayed manner, even without any symptoms.

A new perspective on the therapeutic potential of tumor metastasis: targeting the metabolic interactions between TAMs and tumor cells.

Tumor-associated macrophages (TAMs) undergo metabolic reprogramming, encompassing glucose, amino acid, fatty acid metabolism, tricarboxylic acid (TCA) cycle, purine metabolism, and autophagy, within the tumor microenvironment (TME). The metabolic interdependencies between TAMs and tumor cells critically influence macrophage recruitment, differentiation, M2 polarization, and secretion of epithelial-mesenchymal transition (EMT)-related factors, thereby activating intratumoral EMT pathways and enhancing tumor cell invasion and metastasis. Tumor cell metabolic alterations, including hypoxia, metabolite secretion, aerobic metabolism, and autophagy, affect the TME's metabolic landscape, driving macrophage recruitment, differentiation, M2 polarization, and metabolic reprogramming, ultimately facilitating EMT, invasion, and metastasis. Additionally, macrophages can induce tumor cell EMT by reprogramming their aerobic glycolysis. Recent experimental and clinical studies have focused on the metabolic interactions between macrophages and tumor cells to control metastasis and inhibit tumor progression. This review highlights the regulatory role of TAM-tumor cell metabolic codependencies in EMT, offering valuable insights for TAM-targeted therapies in highly metastatic tumors. Modulating the metabolic interplay between tumors and TAMs represents a promising therapeutic strategy for treating patients with metastatic cancers.

Machine learning-based radiomics in neurodegenerative and cerebrovascular disease.

Cognitive impairments, which can be caused by neurodegenerative and cerebrovascular disease, represent a growing global health crisis with far-reaching implications for individuals, families, healthcare systems, and economies worldwide. Notably, neurodegenerative-induced cognitive impairment often presents a different pattern and severity compared to cerebrovascular-induced cognitive impairment. With the development of computational technology, machine learning techniques have developed rapidly, which offers a powerful tool in radiomic analysis, allowing a more comprehensive model that can handle high-dimensional, multivariate data compared to the traditional approach. Such models allow the prediction of the disease development, as well as accurately classify disease from overlapping symptoms, therefore facilitating clinical decision making. This review will focus on the application of machine learning-based radiomics on cognitive impairment caused by neurogenerative and cerebrovascular disease. Within the neurodegenerative category, this review primarily focuses on Alzheimer's disease, while also covering other conditions such as Parkinson's disease, Lewy body dementia, and Huntington's disease. In the cerebrovascular category, we concentrate on poststroke cognitive impairment, including ischemic and hemorrhagic stroke, with additional attention given to small vessel disease and moyamoya disease. We also review the specific challenges and limitations when applying machine learning radiomics, and provide our suggestion to overcome those limitations towards the end, and discuss what could be done for future clinical use.

Retrograde transurethral injection of indocyanine green better assists complete transperitoneal nephroureterectomy in a single-position.

Background: Complete transperitoneal nephroureterectomy (CTNU) in a single-position is an advanced surgical technique for the treatment of upper urinary tract urothelial carcinoma (UTUC), performed entirely through a transperitoneal approach without the need for patient repositioning. Indocyanine green (ICG) has been extensively studied in urologic surgery, with applications ranging from sentinel lymph node mapping to tumor localization. This study aimed to evaluate the performance of retrograde ureteral fluorescence imaging in CTNU. Methods: This retrospective cohort enrolled 81 patients diagnosed with UTUC and underwent single-position CTNU. Cohorts were divided into two groups according to whether the ICG was applied. Perioperative data and oncology outcomes were recorded and analyzed. Results: In total, 81 eligible participants were finally included, with 40 in the ICG group and 41 in the non-ICG group. The ICG group presented significantly shorter ureter identification time (8.5±3.3 vs. 17.3±4.2 min, P<0.001) and duration of surgery (132±40 vs. 162±49 min, P=0.003), as well as lower estimated blood loss (EBL) (108±94 vs. 183±126 mL, P=0.003) compared to the non-ICG group. The rates of intravesical and extravesical carcinoma recurrence were comparable between the two groups. At a median follow-up of 16.7 months, there were no significant differences in terms of the recurrence-free survival (RFS) and overall survival (OS) between groups. Conclusions: ICG guided ureteral fluorescence imaging in single-position CTNU showed significant advantages in precisely and effectively locating the ureter, with improved surgical outcomes. Meanwhile, the enhanced visualization of the ureteral intramural segment and bladder cuff facilitated the complete removal of the specimen en bloc and the watertight closure of the bladder.

Elaeagnus angustifolia L. fruit alleviates diarrhea via regulating intestinal microbiota and short chain fatty acids.

Fruits of Elaeagnus angustifolia L. have been used as Uyghur medicine due to the properties of treating spleen and stomach weakness, indigestion, enteritis, diarrhea, lung heat, and cough. However, the anti-diarrhea mechanism was still not clear. This study explored the mechanism of E. angustifolia fruit alleviated diarrhea from the perspective of gut microbiota. Diarrhea model was established with Folium sennae in mice. Then, the levels of diarrhea rate and diarrhea index of mice were evaluated. Hematoxylin eosin (HE) staining was employed to detect pathological sections of colon tissue. 16S rRNA sequencing analysis was researched to confirm the gut microbiota in mice. Diversity and differential analysis were adopted to analyze the intestinal microflora. Furthermore, Gas chromatography-quadrupole time-of-flight tandem mass spectrometry (GC-Q-TOF-MS) was used to detect the concentrations of short chain fatty acids (SCFAs) in intestine. The high-dose group (3.2 g/kg) of E. angustifolia fruit could significantly reduce the diarrhea rate and diarrhea index of mice caused by Folium sennae (p < 0.01). We also found that E. angustifolia fruit enhanced the diversity of gut microbiota while ameliorating diarrhea. Alpha diversity revealed that the microbial composition of E. angustifolia fruit group tended to be more similar to that of the CON group (no significant difference at p < 0.05). E. angustifolia fruit also induced structural changes of gut microbiota in mice. In addition, the concentrations of SCFAs increased after administration of E. angustifolia fruit. This study demonstrated that E. angustifolia fruit could ameliorate diarrhea by regulating the composition and abundance of intestinal microbiota, together with the levels of SCFAs.

Outcomes of Post-Immunotherapy Durable Responders of Advanced Hepatocellular Carcinoma- with Emphasis on Locoregional Therapy for Oligoprogression.

Introduction: The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized. Methods: Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤3 and >3 lesions, respectively. Results: A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis (n = 69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second- or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1-58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p = 0.009; multivariate analysis: HR 0.363, p = 0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p < 0.001). In contrast, the median OS of patients with polyprogression who received LRT was not different from those without LRT (27.7 vs. 25.5 months, p = 0.794). Conclusion: Approximately 60% of the post-immunotherapy durable responders of HCC subsequently develop progression. Proactive LRT may further rescue patients who develop subsequent oligoprogression. Prospective studies are mandatory to clarify the proper management of durable responders with subsequent progression.

Management Consensus Guidelines for Hepatocellular Carcinoma: 2023 Update on Surveillance, Diagnosis, Systemic Treatment, and Posttreatment Monitoring by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan established HCC management consensus guidelines in 2016 and updated them in 2023. Current recommendations focus on addressing critical issues in HCC management, including surveillance, diagnosis, systemic treatment, and posttreatment monitoring. For surveillance and diagnosis, we updated the guidelines to include the role of protein induced by vitamin K absence or antagonist II (PIVKA-II) and gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting HCCs. For systemic treatment, the updated guidelines summarize the multiple choices available for targeted therapy, immune checkpoint inhibitors, and a combination of both, especially for those carcinomas refractory to or unsuitable for transarterial chemoembolization. We have added a new section, posttreatment monitoring, that describes the important roles of PIVKA-II and EOB-MRI after HCC therapy, including surgery, locoregional therapy, and systemic treatment. Through this update of the management consensus guidelines, patients with HCC may benefit from optimal diagnosis, therapeutic modalities, and posttreatment monitoring.

Visualizing Ultrafast Photogenerated Electron and Hole Separation in Facet-Engineered Bismuth Vanadate Crystals.

Photogenerated charge separation is pivotal for effecting efficient photocatalytic reactions. Understanding this process with spatiotemporal resolution is vital for devising highly efficient photocatalysts. Here, we employed pump-probe transient reflection microscopy to directly observe the temporal and spatial evolution of photogenerated electrons and holes on the surface of facet-engineered bismuth vanadate (BiVO4) crystals. The findings suggest that the anisotropic built-in field of BiVO4 crystals propels the separation of photogenerated electrons and holes toward different facets through a two-step process across varying time scales. Photogenerated electrons and holes undergo ultrafast separation within ∼6 ps, with electrons transforming into localized small polarons toward the {010} facets of truncated BiVO4 octahedral crystals. However, the photogenerated holes prolong their separation up to ∼2000 ps in a drift-diffusion manner before ultimately accumulating on the {120} facets. This work provides a comprehensive visualization of spatiotemporal charge separation at the nano/microscale on semiconductor photocatalysts, which is beneficial for understanding the photocatalysis mechanism.