Dual-Drug Nanomedicine Assembly with Synergistic Anti-Aneurysmal Effects via Inflammation Suppression and Extracellular Matrix Stabilization.

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.

Asperuloside inhibits the activation of pancreatic cancer-associated fibroblasts via activating transcription factor 6.

BACKGROUND: Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress. METHOD: CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C-C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP. CONCLUSION: ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment.

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

Research Status and Development Trend of Coal Spontaneous Combustion Fire and Prevention Technology in China: A Review.

Coal seam spontaneous combustion fire is not only one of the main forms of the five major mine disasters, but also the main cause of secondary disasters such as mine gas and coal dust explosions. In recent years, with the advancement of mechanization, automation, and intelligent mine construction, spontaneous coal fires in mines have presented a series of new characteristics, and the prevention and control of spontaneous coal fires are also facing new challenges. On the basis of literature research, this paper summarizes and discusses the basic theory of coal spontaneous combustion, monitoring and early warning methods, and prevention and control technology, summarizes the development process of coal spontaneous combustion theory, reviews the research progress of coal spontaneous combustion monitoring and early warning methods and prevention and control technologies, and discusses the future development direction. In terms of the basic theory of spontaneous combustion of coal, from the initial hypothesis of spontaneous combustion of multielement coal to the unified understanding of coal-oxygen composite theory, a complete set of theoretical systems have been established, and a lot of macro and micro studies have been carried out and analyzed from multiple perspectives. In terms of coal spontaneous combustion monitoring and early warning, from the initial single indicator gas early warning to the construction of gas index system, the hierarchical early warning system is studied, and gradually tends to be perfect. With the development of automation and intelligence technology, the monitoring of coal spontaneous combustion disasters has also formed a new monitoring technology with beam tube monitoring as the traditional method, distributed optical fiber, wireless AD hoc network temperature measurement, and a coal spontaneous combustion multiparameter wireless monitoring system. In terms of fire prevention and control, the traditional "prevention" and "treatment" have changed to the "prevention-control-extinction" technical system based on hierarchical early warning, and the focus has gradually shifted to "prevention", and a large number of antifire materials have been developed, including blocking materials and fire-fighting materials. However, the precise inhibition and control of coal spontaneous combustion disasters, the evolution model of coal spontaneous combustion under the conditions of multifactor coupling in the field, the reliability and stability of intelligent monitoring system, the noncontact detection method of fire source, and the collaborative adaptation of multiple prevention and control techniques are not yet clear. In the future development, the mechanism of spontaneous coal combustion and its evolution process and other basic theories should be deeply studied. On the basis of the mechanism optimization early warning method of spontaneous coal combustion process, flame retardant and fire prevention materials should be targeted and developed. On the basis of the spatiotemporal evolution of spontaneous coal combustion, monitoring and monitoring system equipment with high speed, high precision, and high stability should be developed, which should accelerate the realization of accurate dynamic sensing and intelligent early warning of coal spontaneous combustion, and form an active hierarchical collaborative prevention and control system based on the trinity of "prevention-control-extinction" of coal spontaneous combustion. The conclusions and prospects of this paper can be used for reference in the future research direction, and have a certain role in promoting the exchange of research results of coal science and technology workers.

Study on the Inhibition Characteristics of Coal Spontaneous Combustion by Silica Gel Foam.

The spontaneous combustion of residual coal in abandoned mining areas severely affects the safe and efficient extraction of coal, employee occupational health, and regional environmental ecology. A technical measure for preventing and controlling the spontaneous combustion of residual coal involves injecting antispontaneous combustion materials into abandoned areas. In this study, the composition, preparation, and mechanism of action of silica gel foam, a material used to suppress spontaneous combustion during coal mining, were investigated to improve the performance of materials designed to prevent spontaneous combustion in abandoned areas. The inhibitory efficiency improved, and the mechanical strength and stability of the foam liquid film increased upon adding modified antioxidants and nanosilica particles to the gel foam. Macro performance tests, microstructural characterization, and chemical inhibition mechanism analyses verified the efficacy of silica gel foam for suppressing spontaneous combustion. The air leakage resistance of the silica gel foam effectively increased the air leakage resistance of the coal samples at different pressures. New radicals formed during the spontaneous combustion of coal comprising different inhibitors, as indicated by the g-factor results of electron paramagnetic resonance (EPR) spectroscopy analysis; the formation of radicals initially decreased and then increased when the inhibitor material changed. The concentration of free radicals decreased markedly during the spontaneous combustion process of both raw and inhibited coal samples at low oxidation temperatures (∼60-100 °C), indicating a marked inhibitory effect.

Long-term follow-up of non-myasthenic patients with early-stage thymoma who underwent extended thymectomy or limited resection.

BACKGROUD: The standard resection for early-stage thymoma is total thymectomy and complete tumour excision with or without myasthenia gravis but the optimal surgery mode for patients with early-stage non-myasthenic thymoma is debatable. This study analysed the oncological outcomes for non-myasthenic patients with early-stage thymoma treated by thymectomy or limited resection in the long term. METHODS: Patients who had resections of thymic neoplasms at Taipei Veteran General Hospital, Taiwan between December 1997 and March 2013 were recruited, exclusive of those combined clinical evidence of myasthenia gravis were reviewed. A total of 113 patients were retrospectively reviewed with pathologic early stage (Masaoka stage I and II) thymoma who underwent limited resection or extended thymectomy to compare their long-term oncologic and surgical outcomes. RESULTS: The median observation time was 134.1 months [interquartile range (IQR) 90.7-176.1 months]. In our cohort, 52 patients underwent extended thymectomy and 61 patients underwent limited resection. Shorter duration of surgery (p < 0.001) and length of stay (p = 0.006) were demonstrated in limited resection group. Six patients experienced thymoma recurrence, two of which had combined myasthenia gravis development after recurrence. There was no significant difference (p = 0.851) in freedom-from-recurrence, with similar 10-year freedom-from-recurrence rates between the limited resection group (96.2 %) and the thymectomy group (93.2 %). Tumour-related survival was also not significantly different between groups (p = 0.726).result CONCLUSION: Patients with early-stage non-myasthenic thymoma who underwent limited resection without complete excision of the thymus achieved similar oncologic outcomes during the long-term follow-up and better peri-operative results compared to those who underwent thymectomy.

Role of SIRTl/Nrf2/HO-l pathway in attenuation of learning and memory impairment by sevoflurane postcondition in a mouse model of hemorrhagic shock and resuscitation / 中国药理学通报

Aim To explore the role of SIRT1/Nrf2 / HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion. Methods C57BL/6J mice were randomly divided into five groups: sham operation group, hemorrhagic shock reperfusion group, sevoflurane postconditioning group, sevoflurane postcondition-ing + SIRT1 inhibitor group and sevoflurane postconditioning + Nrf2 inhibitor group. Mice were subjected to Morris water maze test after cerebral ischemia reperfusion. The ATP, superoxide dismutase (SOD), ROS and MDA contents in tissue of mice were detected. SIRT1, Nrf2 and HO-1 proteins in tissue were detected by Western blot. Results After hemorrhagic shock, the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced , MDA and ROS concentration increased, and the SIRT, Nrf2 and HO-1 concentration was reduced. Sevoflurane improved the cognitive dysfunction and oxi-dative damage in postoperative mice, and the neuro-protective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors. Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/H0-1 pathway.

The intramolecular SN2 reaction tautomeric ent-Kauranoids isolated from the aerial parts of Isodon amethystoides.

As our ongoing searching for the bioactive natural terpenoids, nine ent-kauranoids (1-9), including three previously undescribed ones (1, 2, and 9), were isolated from the aerial parts of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic data analysis, including NMR, MS, and ECD. Compounds 1 and 2 were a pair of tautomeric compounds, which was confirmed by the HPLC analysis and low temperature NMR testing. The underlying mechanism of the tautomer was proposed as an intramolecular SN2 reaction, which was explained by quantum chemical calculation. The HOMO-LUMO gap and the free energy revealed the spontaneous of the tautomeric of the 1 and 2. Additionally, the similar phenomena were also found in the two groups of known compounds 3 and 4 and 6 and 7, respectively. Apart from the tautomer, compounds 3 and 4 can be hydrolyzed into 5 through ester hydrolysis in CDCl3, while compounds 6, 7 can be hydrolyzed into 8 through ester hydrolysis. These phenomena were also confirmed through HPLC analysis and low temperature nuclear magnetic resonance tests and the mechanism was studied using quantum chemical calculation.

Nirmatrelvir/ritonavir use in patients with COVID-19 on hemodialysis: a case series.

Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to 4 patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.

The magnetic resonance characteristics of sinonasal rhabdomyosarcoma in adults: analysis of 27 cases and comparison with pathological subtypes.

BACKGROUND: Sinonasal rhabdomyosarcoma (RMS) in adults is extremely rare, and early diagnosis and treatment are crucial to improve the patient's prognosis. The purpose of this study was to evaluate the magnetic resonance imaging (MRI) findings of sinonasal RMS in adults and analyze the correlations between the imaging features and pathological subtypes. METHODS: We reviewed 27 patients with pathologically proven RMS of the nasal cavity and paranasal sinuses, including embryonal RMS (ERMS) in 14 patients, alveolar RMS (ARMS) in seven patients, and mixed-type RMS in six patients. Conventional MRI was performed in all 27 patients, and high-resolution diffusion-weighted imaging was conducted in 25 patients. The tumor location, size, morphological features, signal intensity, texture, contrast enhancement characteristics, lymph node metastases, apparent diffusion coefficients (ADCs), and involvement of local soft tissues were independently assessed by two authors. RESULTS: On MR imaging, sinonasal RMS appeared isointense on T1-weighted imaging in 21 cases (77.8%) and heterogeneously hyperintense on T2-weighted imaging in 18 patients (66.7%). After enhancement, the tumors were heterogeneously enhanced in 24 cases (88.9%). Botryoid enhancement with multiple small rings resembling bunches of grapes was found in 15 cases (55.6%). Mucosal invasion of the maxillary sinus was identified in 51.9% patients. Skull and orbit involvement were found in 55.6% and 81.5% patients, respectively. Lymph node metastasis was seen in 18 cases (66.7%). There were significant differences in botryoid enhancement (P = 0.044) and skull involvement (P = 0.044) among different histological subtypes. The mean ADC value of RMS was 0.73 ± 0.082 × 10-3 mm2/s, and there was no significant difference among different histological subtypes. CONCLUSIONS: Some characteristic MRI findings such as botryoid enhancement in the ethmoid sinus, involvement of the orbit and skull, and a lower ADC value can provide important clues for preoperative diagnosis of sinonasal RMS in adults. Further, botryoid enhancement was more common in ERMS, while skull involvement was more common in ARMS.

Relationships Between Gaming Disorder, Risk Factors, and Protective Factors Among a Sample of Chinese University Students Utilizing a Network Perspective.

Research has demonstrated that some risk and protective factors of gaming disorder (GD) have been identified. However, the interaction of GD with risk and protective factors has rarely been examined from a network analysis perspective. Therefore, the present study examined the relationships between GD, risk factors (i.e., social anxiety and fear of missing out), and protective factors (i.e., resilience, authenticity, and family closeness) utilizing a network analysis approach among a sample of Chinese university students. A cross-sectional study with 1364 participants was performed using the Gaming Disorder Test, the short version of Social Interaction Anxiety Scale (SIAS), the Chinese Trait-State Fear of Missing Out Scale (T-SFoMOSC), the Brief Resilience Scale (BRS), the Authenticity Scale, and a single item assessing family closeness. Social anxiety, FoMO, and two factors of authenticity (i.e., self-alienation and accepting external influence) had positive relationship with GD, while resilience, authentic living, and family closeness had negative relationship with GD. Social anxiety was identified as the core node in the domain-level network. The item "continuation or escalation of gaming" (gd3) and the item "gaming problems" (gd4) constituted the highest edge weight in the facet-level network. The network comparison demonstrated there were no significant differences in relation to network structures and global strengths between gender. The findings suggest bivariate relationships among GD, risk factors (i.e., social anxiety and fear of missing out), and protective factors (i.e., resilience, authenticity, and family closeness). Interventions for GD must be considered through preventing risk factors and increasing protective factors including improving the gaming motivation and maladaptive cognition to decrease negative emotion (e.g., social anxiety and FoMO), enhancing resilience, authentic living and parent-child relationship, as well as decreasing self-alienation and accepting external influence. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-023-01049-3.

Bioinformatics analysis of potential key ferroptosis-related genes involved in tubulointerstitial injury in patients with diabetic nephropathy.

Diabetic nephropathy (DN) is the primary complication of diabetes mellitus. Ferroptosis is a form of cell death that plays an important role in DN tubulointerstitial injury, but the specific molecular mechanism remains unclear. Here, we downloaded the DN tubulointerstitial datasets GSE104954 and GSE30529 from the Gene Expression Omnibus database. We examined the differentially expressed genes (DEGs) between DN patients and healthy controls, and 36 ferroptosis-related DEGs were selected. Pathway-enrichment analyses showed that many of these genes are involved in metabolic pathways, phosphoinositide 3-kinase/Akt signaling, and hypoxia-inducible factor-1 signaling. Ten of the 36 ferroptosis-related DEGs (CD44, PTEN, CDKN1A, DPP4, DUSP1, CYBB, DDIT3, ALOX5, VEGFA, and NCF2) were identified as key genes. Expression patterns for six of these (CD44, PTEN, DDIT3, ALOX5, VEGFA, and NCF2) were validated in the GSE30529 dataset. Nephroseq data indicated that the mRNA expression levels of CD44, PTEN, ALOX5, and NCF2 were negatively correlated with the glomerular filtration rate (GFR), while VEGFA and DDIT3 mRNA expression levels were positively correlated with GFR. Immune infiltration analysis demonstrated altered immunity in DN patients. Real-time quantitative PCR (qPCR) analysis showed that ALOX5, PTEN, and NCF2 mRNA levels were significantly upregulated in high-glucose-treated human proximal tubular (HK-2) cells, while DDIT3 and VEGFA mRNA levels were significantly downregulated. Immunohistochemistry analysis of human renal biopsies showed positive staining for ALOX5 and NCF2 protein in DN samples but not the controls. These key genes may be involved in the molecular mechanisms underlying ferroptosis in patients with DN, potentially through specific metabolic pathways and immune/inflammatory mechanisms.

Lipoprotein-Associated Phospholipase A2 Correlates with Reduced Left Ventricle Ejection Fraction in Hemodialysis Patients.

OBJECTIVE: Reduced left ventricular ejection fraction (LVEF) is common in hemodialysis (HD) patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered an important determinant of cardiovascular events. The aim of the study was to evaluate the relationship between Lp-PLA2 and LVEF in HD patients. METHODS: Fifty-seven HD patients with coronary heart disease were enrolled. Predialysis and postdialysis venous whole blood samples were collected. The patients were divided into preserved and reduced LVEF groups. The relationship between Lp-PLA2 and LVEF was assessed. RESULTS: A significant difference in C-reactive protein (CRP) and Lp-PLA2 was observed, with higher levels noted in patients with reduced LVEF (P ≤ .001). Both Lp-PLA2 and CRP were negatively correlated with LVEF in the HD patients. Only Lp-PLA2 remained associated with LVEF in multiple regression analysis. CONCLUSION: Lipoprotein-associated phospholipase A2 levels are associated with LVEF and could potentially be used to evaluate chronic heart failure with reduced LVEF in HD patients for risk stratification management.

The Value of Peripheral Blood Cell Ratios in Primary Membranous Nephropathy: A Single Center Retrospective Study.

Background: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Forty percent of the patients continue to progress and eventually develop into chronic renal failure. Although phospholipase A2 receptor (PLA2R) is the major antigen of PMN, the clinical features do not often parallel with the antibody titers. Therefore, it is significant to find relative credible markers to predict the treatment response. Methods: One hundred and eighteen PMN patients were recruited. The response to treatment was defined as ALB≥30g/L at 6 months and complete remission (CR) or not at the end of the follow-up. Renal outcome endpoint was defined as 50% or more Cr increase at the end. Results: The patients with poor treatment effects had numerically higher platelet-lymphocytes ratio (PLR). For patients with CR or not, the difference was near to statistic significant (P=0.095). When analyzing CR or not, the fitting of the binary logistic regression model including both PLA2R Ab titer and PLR (Hosmer-Lemeshow test: χ 2=8.328, P = 0.402; OR (PLA2R Ab titer) = 1.002 (95% CI 1.000-1.004, P = 0.042); OR (PLR) = 1.006 (95% CI 0.999-1.013, P = 0.098)) was markedly better than that with only PLA2R Ab titer (Hosmer-Lemeshow test: χ 2=13.885, P = 0.016). The patients with renal function deterioration showed significantly higher monocyte-lymphocyte ratio (MLR) (0.26 (0.22-0.31) vs 0.18 (0.13-0.22), P = 0.012). Conclusion: PMN patients with poor treatment response tended to have higher PLR at the time of renal biopsy, and a higher MLR was associated with poor renal outcomes. Our findings suggested that PLR and MLR might be used to predict treatment efficacy and prognosis for PMN patients, respectively.

A Benzothiadiazole-Based Self-Assembled Cage for Cadmium Detection.

A turn-on fluorescent probe, cage 1, was efficiently self-assembled by condensing 4,4'-(benzothiadiazole-4,7-diyl)dibenzaldehyde and TREN in chloroform. The formation of cage 1 was characterized and confirmed by NMR spectroscopy, mass spectrometry, and theoretical calculations. The yield of cage 1 could be controlled by tuning the reaction conditions, such as the precursor concentration. Interestingly, the addition of 10 equiv of Cd2+ relative to cage 1 could increase the fluorescence almost seven-fold. 1H NMR and fluorescence experiments indicating fluorescence enhancement may be caused by the decomposition of cage 1. Such a high selectivity toward Cd2+ implies that the cage could potentially be employed in cadmium detection.

Bacteria and filamentous fungi running a relay race in Daqu fermentation enable macromolecular degradation and flavor substance formation.

As the saccharifying and fermentative agent, medium-temperature Daqu (MT-Daqu) plays an irreplaceable role in the production of strong-flavor Baijiu. Numerous studies have focused on the microbial community structure and potential functional microorganisms, however, little is known about the succession of active microbial community and the formation mechanism of community function during MT-Daqu fermentation. In this study, we presented an integrated analysis of metagenomics, metatranscriptomics, and metabonomics covering the whole fermentation process of MT-Daqu to reveal the active microorganisms and their participations in metabolic networks. The results showed that dynamic of metabolites were time-specific, and the metabolites and co-expressed active unigenes were further classified into four clusters according to their accumulation patterns, with members within each cluster displaying a uniform and clear pattern of abundance across fermentation. Based on KEGG enrichment analysis in co-expression clusters and succession of active microbial community, we revealed that Limosilactobacillus, Staphylococcus, Pichia, Rhizopus, and Lichtheimia were metabolically active members at the early stage, and their metabolic activities were conducive to releasing abundant energy to drive multiple basal metabolisms such as carbohydrates and amino acids. Thereafter, during the high temperature period and at the end of fermentation, multiple heat-resistant filamentous fungi were transcriptionally active populations, and they acted as both the saccharifying agents and flavor compound producers, especially aromatic compounds, suggesting their crucial contribution to enzymatic activity and aroma of mature MT-Daqu. Our findings revealed the succession and metabolic functions of the active microbial community, providing a deeper understanding of their contribution to MT-Daqu ecosystem.

Middle Ear Teratoma: Clinical and Imaging Features.

BACKGROUND: Teratoma is a true neoplasm composed of a number of different types of tissue derived from the three germinal layers but rarely occurs in the middle ear (ME). The features of middle ear teratomas (MET) have not been well described. OBJECTIVE: The objective of this study is to explore the clinical and imaging features of MET, and report 2 rare cases of MET with ear malformation that have never been reported. MATERIALS AND METHODS: The clinical, CT and MRI data of 8 patients with a pathological diagnosis of MET were collected and retrospectively mined, and 14 patients with MET reported in previous literature were also reviewed. RESULTS: ① Female, left ear predominance in MET, and the most common symptoms were otorrhea and hearing loss. ② On CT and MRI, the MET presented as an irregular soft tissue mass that was heterogeneous, with fatty tissue and involved multiple sites, and the ET and tympanum were correspondingly expanded and locally destroyed. ③ Mictotia with MET in two patients was presented, which was the first report. CONCLUSION: MET has female sex and left ear predominance. CT and MRI can be used to diagnose MET and display its extent and its relationship to the carotid canal in detail. Complete surgical excision is the definitive treatment.

Modified En Bloc Esophagectomy for Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

BACKGROUND: The optimal type of esophagectomy and extent of lymphadenectomy for patients after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma remain controversial. We hypothesized that a more radical resection is associated with better survival. METHODS: Data of patients who received nCRT followed by resection for esophageal squamous cell carcinoma between 2012 and 2021 were analyzed. Modified en bloc esophagectomy (mEBE) involves total mediastinal lymphadenectomy and resection of all periesophageal node-bearing tissues. Perioperative outcomes and survival rates of mEBE were compared with those of conventional esophagectomy (CE). RESULTS: A total of 238 patients were included. Compared with CE, mEBE was associated with a longer operative time, higher total number of resected lymph nodes, fewer complications, and less anastomotic leakage; length of stay was similar between the 2 groups. There was no difference in overall survival rates between patients with ypT0 N0 stage in the mEBE and CE groups; however, in patients with non-ypT0 N0 stage in the mEBE and CE groups, the 3-year overall survival rates were 58.5% and 28.5%, respectively (P < .001). On disease-free survival analysis, no difference was observed in patients with ypT0 N0 stage, whereas patients with non-ypT0 N0 stage after nCRT had significantly better disease-free survival after mEBE compared with CE (49.7% vs 27.2%; P = .017). CONCLUSIONS: Survival after mEBE was significantly better than that after CE. The mEBE did not increase postoperative hospital stay and complication rates.

Old age and EGFR mutation status in inoperable early-stage non-small cell lung cancer patients receiving stereotactic ablative radiotherapy: A single institute experience of 71 patients in Taiwan.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is now the standard of care for patients with inoperable early-stage lung cancer. Many of these patients are elderly. EGFR (epidermal growth factor receptor) mutation is also common in the Asian population. METHODS: To evaluate the effects of old age and EGFR mutation on treatment outcomes and toxicity, we reviewed the medical records of 71 consecutive patients with inoperable early-stage non-small cell lung cancer (NSCLC) who received SABR at Taipei Veterans General Hospital between 2015 and 2021. RESULTS: The study revealed that median age, follow-up, Charlson comorbidity index, and ECOG score were 80 years, 2.48 years, 3, and 1, respectively. Of these patients, 37 (52.1%) were 80 years or older, and 50 (70.4%) and 21 (29.6%) had T1 and T2 diseases, respectively. EGFR mutation status was available for 33 (46.5%) patients, of whom 16 (51.5%) had a mutation. The overall survival rates at 1, 3, and 5 years were 97.2, 74.9, and 58.3%, respectively. The local control rate at 1, 3, and 5 years was 97.1, 92.5, and 92.5%, respectively. Using Cox proportional hazards regression we found that male sex was a risk factor for overall survival (p = 0.036, 95% CI: 1.118-26.188). Two patients had grade 2 pneumonitis, but no other grade 2 or higher toxicity was observed. We did not find any significant differences in treatment outcomes or toxicity between patients aged 80 or older and those with EGFR mutations in this cohort. CONCLUSION: These findings indicate that age and EGFR mutation status do not significantly affect the effectiveness or toxicity of SABR for patients with inoperable early-stage NSCLC.