Pneumococcal vaccination and primary care presentations for acute respiratory tract infection and antibiotic prescribing in older adults.

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.

Risk factors for and outcomes of heatstroke-related intracerebral hemorrhage.

Some patients with heatstroke also experience intracerebral hemorrhage (ICH). However, clinical case reports of heatstroke-induced ICH are rare. The risk factors for cerebral hemorrhage after heatstroke remain unknown. The present study evaluated the clinical characteristics and risk factors of patients with heatstroke-related ICH. In this retrospective observational study, we collected data on all ICHs after heatstroke occurred between 2012 and 2022. The characteristics of patients with heatstroke-induced ICH were described. The risk factors for cerebral hemorrhage after heatstroke were examined using logistic regression analysis. In total, 177 patients were included in this study, and 11 patients with ICH secondary to heatstroke were identified. Variables with P values of <.05 in univariate models, comparing the cerebral hemorrhage and control groups, included heatstroke cause, temperature, heart rate, respiratory rate, vasopressor use, mechanical ventilation use, Acute Physiology and Chronic Health Evaluation II, total bilirubin, creatinine, platelet count, prothrombin time, procalcitonin, creatine kinase, disseminated intravascular coagulation (DIC) occurrence, and DIC score. Multivariate logistic regression showed that heatstroke patients with higher DIC scores (odds ratio, 18.402, 95% confidence interval, 1.384-244.763, P = .027) and higher creatine kinase levels (odds ratio, 1.021, 95% confidence interval, 1.002-1.041, P = .033) were at a higher risk of developing ICH. The death rate was higher in the cerebral hemorrhage group than in the control group (P = .042). Heatstroke-related cerebral hemorrhage may be associated with elevated creatinine levels and DIC severity (International Society on Thrombosis and Hemostasis score) after heatstroke, and heatstroke with cerebral hemorrhage may accelerate death.

Molecular network mechanism in cerebral ischemia-reperfusion rats treated with human urine stem cells.

Objective: To explore the effect of human urine-derived stem cells (husc) in improving the neurological function of rats with cerebral ischemia-reperfusion (CIR), and report new molecular network by bioinformatics, combined with experiment validation. Methods: After CIR model was established, and husc were transplanted into the lateral ventricle of rats，neurological severe score (NSS) andgene network analysis were performed. Firstly, we input the keywords "Cerebral reperfusion" and "human urine stem cells" into Genecard database and merged data with findings from PubMed so as to get their targets genes, and downloaded them to make Venny intersection plot. Then, Gene ontology (GO) analysis, kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein-protein interaction (PPI) were performed to construct molecular network of core genes. Lastly, the expressional level of core genes was validated via quantitative real-time polymerase chain reaction (qRT-PCR), and localized by immunofluorescence. Results: Compared with the Sham group, the neurological function of CIR rats was significantly improved after the injection of husc into the lateral ventricle; at 14 days, P = 0.028, which was statistically significant. There were 258 overlapping genes between CIR and husc, and integrated with 252 genes screened from PubMed and CNKI. GO enrichment analysis were mainly involved neutrophil degranulation, neutrophil activation in immune response and platelet positive regulation of degranulation, Hemostasis, blood coagulation, coagulation, etc. KEGG pathway analysis was mainly involved in complement and coagulation cascades, ECM-receptor. Hub genes screened by Cytoscape consist ofCD44, ACTB, FN1, ITGB1, PLG, CASP3, ALB, HSP90AA1, EGF, GAPDH. Lastly, qRT-PCR results showed statistic significance (P < 0.05) in ALB, CD44 and EGF before and after treatment, and EGF immunostaining was localized in neuron of cortex. Conclusion: husc transplantation showed a positive effect in improving neural function of CIR rats, and underlying mechanism is involved in CD44, ALB, and EGF network.

Electrochemical Synthesis of C(sp3)-Rich Amines by Aminative Carbofunctionalization of Carbonyl Compounds.

Alkylamines form the backbone of countless nitrogen-containing small molecules possessing desirable biological properties. Despite advances in amine synthesis through transition metal catalysis and photoredox chemistry, multicomponent reactions that leverage inexpensive materials to transform abundant chemical feedstocks into three-dimensional α-substituted alkylamines bearing complex substitution patterns remain scarce. Here, we report the design of a catalyst-free electroreductive manifold that merges amines, carbonyl compounds and carbon-based radical acceptors under ambient conditions without rigorous exclusion of air and moisture. Key to this aminative carbofunctionalization process is the chemoselective generation of nucleophilic α-amino radical intermediates that readily couple with electrophilic partners, providing straightforward access to architecturally intricate alkylamines and drug-like scaffolds which are inaccessible by conventional means.

In Situ Atomic Reconstruction Engineering Modulating Graphene-Like MXene-Based Multifunctional Electromagnetic Devices Covering Multi-Spectrum.

With the diversified development of big data, detection and precision guidance technologies, electromagnetic (EM) functional materials and devices serving multiple spectrums have become a hot topic. Exploring the multispectral response of materials is a challenging and meaningful scientific question. In this study, MXene/TiO2 hybrids with tunable conduction loss and polarization relaxation are fabricated by in situ atomic reconstruction engineering. More importantly, MXene/TiO2 hybrids exhibit adjustable spectral responses in the GHz, infrared and visible spectrums, and several EM devices are constructed based on this. An antenna array provides excellent EM energy harvesting in multiple microwave bands, with |S11| up to - 63.2 dB, and can be tuned by the degree of bending. An ultra-wideband bandpass filter realizes a passband of about 5.4 GHz and effectively suppresses the transmission of EM signals in the stopband. An infrared stealth device has an emissivity of less than 0.2 in the infrared spectrum at wavelengths of 6-14 µm. This work can provide new inspiration for the design and development of multifunctional, multi-spectrum EM devices.

Hepatic portal venous gas initially manifesting as severe shock: a case series.

Hepatic portal venous gas is often referred to as the "sign of death" because it signifies a very poor prognosis if appropriate treatments are not promptly administered. The etiologies of hepatic portal venous gas are diverse and include severe complex abdominal infections, mesenteric ischemia, diving, and complications of endoscopic surgery, and the clinical manifestations are inconsistent among individual patients. Thus, whether emergency surgery should be performed remains controversial. In this report, we present three cases of hepatic portal venous gas. The patients initially exhibited symptoms consistent with severe shock of unknown etiology and were treated in the intensive care unit upon admission. We rapidly identified the cause of each individual patient's condition and selected problem-directed intervention measures based on active organ support, antishock support, and anti-infection treatments. Two patients recovered and were discharged without sequelae, whereas one patient died of refractory infection and multiple organ failure. We hope that this report will serve as a valuable reference for decision-making when critical care physicians encounter similar patients.

Independent effect of the triglyceride-glucose index on all-cause mortality in critically ill patients with chronic obstructive pulmonary disease and asthma: A retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index serves as a reliable proxy for insulin resistance (IR). IR has been linked to heightened incidence, prevalence, or severity of chronic obstructive pulmonary disease (COPD) and asthma. Prior research indicates that critically ill patients are prone to developing IR. Nevertheless, few studies have delved into the correlation between IR and all-cause mortality in critically ill patients with COPD and asthma. Therefore, the aim of this study is to explore the association between the TyG index and all-cause mortality in patients with COPD and asthma, with the goal of assessing the impact of IR on the prognosis of this patient population. METHODS: This is a retrospective study, and all data are from the Medical Information Mart for Intensive Care IV (MIMIC-IV) critical care database. This study included 684 ICU patients with COPD and asthma and divided them into quartiles based on TyG index levels. The primary outcomes of this study were all-cause mortality during follow-up, encompassing mortality at 30 days, 90 days, and 180 days. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality in critically ill patients with COPD and asthma. Restricted cubic spline analysis was used to assess potential nonlinear association between the TyG index and the primary outcome. RESULTS: A total of 684 patients (53.9% female) were included. The 90-days all-cause mortality rate and 180-days all-cause mortality were 11.7% and 12.3%, respectively. Kaplan-Meier analysis revealed a significant association between the TyG index and both 90-days all-cause mortality (log-rank p = .039) and 180-days all-cause mortality (log-rank p = .017). Cox proportional hazards analysis revealed a significant association between the TyG index and 90-days all-cause mortality in both the unadjusted model (HR, 1.30 [95% CI 1.08-1.57] p = .005) and the model adjusted for age, gender, and diabetes (HR, 1.38 [95% CI 1.15-1.67] p < .001). Similarly, the TyG index was associated with 180-days all-cause mortality in the unadjusted model (HR, 1.30 [95% CI 1.09-1.56] p = .004) and the model adjusted for age, sex, and diabetes (HR, 1.38 [95% CI 1.15-1.66] p < .001). The restricted cubic splines (RCS) regression model indicated a significant nonlinear association between the TyG index and both 90-days and 180-days all-cause mortality. Specifically, TyG index >4.8 was associated with an increased risk of mortality at both 90 days and 180 days. CONCLUSIONS: In summary, our results extend the utility of the TyG index to critically ill patients with COPD and asthma. Our study shows that the TyG index is a potential predictor of all-cause mortality in critically ill patients with COPD and asthma. In addition, in patients with a TyG index exceeding 4.8, there was a heightened risk of mortality. Measuring the TyG index may help with risk stratification and prognosis prediction in critically ill patients with COPD and asthma. Further prospective studies are needed to confirm our findings.

Recruitment of HAB1 and SnRK2.2 by C2-domain protein CAR1 in plasma membrane ABA signaling.

Plasma membrane (PM)-associated abscisic acid (ABA) signal transduction is an important component of ABA signaling. The C2-domain ABA-related (CAR) proteins have been reported to play a crucial role in recruiting ABA receptor PYR1/PYL/RCAR (PYLs) to the PM. However, the molecular details of the involvement of CAR proteins in membrane-delimited ABA signal transduction remain unclear. For instance, where this response process takes place and whether any additional members besides PYL are taking part in this signaling process. Here, the GUS-tagged materials for all Arabidopsis CAR members were used to comprehensively visualize the extensive expression patterns of the CAR family genes. Based on the representativeness of CAR1 in response to ABA, we determined to use it as a target to study the function of CAR proteins in PM-associated ABA signaling. Single-particle tracking showed that ABA affected the spatiotemporal dynamics of CAR1. The presence of ABA prolonged the dwell time of CAR1 on the membrane and showed faster lateral mobility. Surprisingly, we verified that CAR1 could directly recruit hypersensitive to ABA1 (HAB1) and SNF1-related protein kinase 2.2 (SnRK2.2) to the PM at both the bulk and single-molecule levels. Furthermore, PM localization of CAR1 was demonstrated to be related to membrane microdomains. Collectively, our study revealed that CARs recruited the three main components of ABA signaling to the PM to respond positively to ABA. This study deepens our understanding of ABA signal transduction.

Decompression sickness followed by diabetic ketoacidosis and sepsis shock: an unusual case report.

Decompression sickness (DCS) is caused by abrupt changes in extracorporeal pressure with varying severity. Symptoms range from mild musculoskeletal pain to severe organ dysfunction and death, especially among patients with chronic underlying disease. Here, we report an unusual case of a 49-year-old man who experienced DCS after a dive to a depth of 38 meters. The patient's symptoms progressed, starting with mild physical discomfort that progressed to disturbance of consciousness on the second morning. During hospitalization, we identified that in addition to DCS, he had also developed diabetic ketoacidosis, septic shock, and rhabdomyolysis. After carefully balancing the benefits and risks, we decided to provide supportive treatment to sustain vital signs, including ventilation support, sugar-reducing therapy, fluid replacement, and anti-infection medications. We then administered delayed hyperbaric oxygen (HBO2) when his condition was stable. Ultimately, the patient recovered without any sequelae. This is the first case report of a diver suffering from DCS followed by diabetic ketoacidosis and septic shock. We have learned that when DCS and other critical illnesses are highly suspected, it is essential to assess the condition comprehensively and focus on the principal contradiction.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Treatment outcomes amongst older people with HIV infection receiving antiretroviral therapy.

OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.

Association rule mining with a special rule coding and dynamic genetic algorithm for air quality impact factors in Beijing, China.

Understanding air quality requires a comprehensive understanding of its various factors. Most of the association rule techniques focuses on high frequency terms, ignoring the potential importance of low- frequency terms and causing unnecessary storage space waste. Therefore, a dynamic genetic association rule mining algorithm is proposed in this paper, which combines the improved dynamic genetic algorithm with the association rule mining algorithm to realize the importance mining of low- frequency terms. Firstly, in the chromosome coding phase of genetic algorithm, an innovative multi-information coding strategy is proposed, which selectively stores similar values of different levels in one storage unit. It avoids storing all the values at once and facilitates efficient mining of valid rules later. Secondly, by weighting the evaluation indicators such as support, confidence and promotion in association rule mining, a new evaluation index is formed, avoiding the need to set a minimum threshold for high-interest rules. Finally, in order to improve the mining performance of the rules, the dynamic crossover rate and mutation rate are set to improve the search efficiency of the algorithm. In the experimental stage, this paper adopts the 2016 annual air quality data set of Beijing to verify the effectiveness of the unit point multi-information coding strategy in reducing the rule storage air, the effectiveness of mining the rules formed by the low frequency item set, and the effectiveness of combining the rule mining algorithm with the swarm intelligence optimization algorithm in terms of search time and convergence. In the experimental stage, this paper adopts the 2016 annual air quality data set of Beijing to verify the effectiveness of the above three aspects. The unit point multi-information coding strategy reduced the rule space storage consumption by 50%, the new evaluation index can mine more interesting rules whose interest level can be up to 90%, while mining the rules formed by the lower frequency terms, and in terms of search time, we reduced it about 20% compared with some meta-heuristic algorithms, while improving convergence.

Characteristics analysis of Internet pharmacy consultation services for children in southwest China during the post-epidemic era: A cross-sectional study.

AIM: This study aims to examine the features of online pediatric pharmacy consultations in Southwest China, an area with limited medical resources during the post-epidemic era and to explore the factors affecting the dialogue volume in online consultations. METHODS: A cross-sectional study was conducted in southwest China from April 2022 to March 2023. The study encompassed a cohort of 2,526 children, ranging from 0 to 18 years old. The collected data encompassed patient gender, age, weight, department, drugs involved in consultation services, types of questions consulted, consultation start time, and the dialogue volume in online consultations. Descriptive statistics and an ordered multicategorical logistic regression analysis were performed. SPSS 26.0 software was used for data analysis. RESULTS: Among the total Internet pharmacy consultation services offered, the infant group constituted the largest portion (n = 1021). Children with internal medicine concerns have greater online consultation needs (n = 455). The peak usage of Internet pharmacy consultation occurred in the fall at 11:00 a.m. (n = 73). Factors influencing the dialogue volume in online consultations include the non-availability of Chinese medications [P = 0.033, OR = 0.81, 95 % CI (0.67-0.98)], consultation initiation during the spring [P = 0.002, OR = 1.52, 95 % CI(1.17-1.97)] or afternoon [P = 0.012, OR = 1.36, 95 % CI (1.07-1.72)] and weight＜15 kg group [P = 0.038, OR = 2.19, 95 % CI (1.04-4.58)]. CONCLUSION: Our findings provide important information for peers to carry out their work. In the post-epidemic era, emphasis should be placed on addressing concerns related to children's internal medicine and otolaryngology. Optimizing healthcare resource allocation should take into account the time-seasonal variability of children's consultation behaviors. Furthermore, it is recommended to focus on weight＜15 kg children in inquiries, absorb sufficient knowledge about Chinese medicines, and schedule more pharmacists to participate in consultation services during the spring or in every afternoon. These findings help the authorities of online platforms and the National Health Commission to rationalize the allocation of healthcare resources, optimize the quality of service delivery, and develop new policies.

Robust treatment planning for small animal radio-neuromodulation using focused kV x-ray beams.

BACKGROUND: In preclinical radio-neuromodulation research, small animal experiments are pivotal for unraveling radiobiological mechanism, investigating prescription and planning techniques, and assessing treatment effects and toxicities. However, the target size inside a rat brain is typically in the order of sub-millimeters. The small target inside the visual cortex neural region in rat brain with a diameter of around 1 mm was focused in this work to observe the physiological change of this region. Delivering uniform doses to the small target while sparing health tissues is challenging. Focused kV x-ray technique based on modern x-ray polycapillary focusing lens is a promising modality for small animal radio-neuromodulation. PURPOSE: The current manual planning method could lead to sub-optimal plans, and the positioning uncertainties due to mechanical accuracy limitations, animal immobilization, and robotic arm motion are not considered. This work aims to design a robust inverse planning method to optimize the intensities of focused kV x-ray beams located in beam trajectories to irradiate small mm-sized targets in rat brains for radio-neuromodulation. METHODS: Focused kV x-ray beams were generated through polycapillary x-ray focusing lenses on achieving small (≤0.3 mm) focus perpendicular to the beam. The beam trajectories were manually designed in 3D space in scanning-while-rotating mode. Geant4 Monte Carlo (MC) simulation generated a dose calculation matrix for each focused kV x-ray beam located in beam trajectories. In the proposed robust inverse planning method, an objective function combining a voxel-wise stochastic programming approach and L1 norm regularization was established to overcome the positioning uncertainties and obtain a high-quality plan. The fast iterative shrinkage thresholding algorithm (FISTA) was utilized to solve the objective function and obtain the optimal intensities. Four cases were employed to validate the feasibility and effectiveness of the proposed method. The manual and non-robust inverse planning methods were also implemented for comparison. RESULTS: The proposed robust inverse planning method achieved superior dose homogeneity and higher robustness against positioning uncertainties. On average, the clinical target volume (CTV) homogeneity index (HI) of robust inverse plan improved to 13.3 from 22.9 in non-robust inverse plan and 53.8 in manual plan if positioning uncertainties were also present. The average bandwidth at D90 was reduced by 6.5 Gy in the robust inverse plan, compared to 9.6 Gy in non-robust inverse plan and 12.5 Gy in manual plan. The average bandwidth at D80 was reduced by 3.4 Gy in robust inverse plan, compared to 5.5 Gy in non-robust inverse plan and 8.5 Gy in manual plan. Moreover, the dose delivery time of manual plan was reduced by an average reduction of 54.7% with robust inverse plan and 29.0% with non-robust inverse plan. CONCLUSION: Compared to manual and non-robust inverse planning methods, the robust inverse planning method improved the dose homogeneity and delivery efficiency and was resistant to the uncertainties, which are crucial for radio-neuromodulation utilizing focused kV x-rays.

The histologic features, molecular features, detection and management of serrated polyps: a review.

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.

Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis.

BACKGROUND: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.

Single-cell transcriptome analysis upon ECM-remodeling meningioma cells.

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.

Five New Species of Gymnopilus from Xizang Autonomous Region of China and Surrounding Areas.

The species of Gymnopilus (Hymenogastraceae, Agricales) are commonly recognized as wood-decaying fungi. Certain members of this genus have been identified as psilocybin-producing mushrooms. Gymnopilus exhibits a diverse range and has a global distribution. In this study, a total of seventy-eight specimens were gathered from ten provinces in China. A comprehensive molecular phylogenetic analysis was conducted, employing gene sequences including ITS, nrLSU, nrSSU, rpb1, rpb2, and tef1-α. Additionally, morphological examinations were also carried out. The phylogenetic topology of Gymnopilus from this study generally agreed with previous studies and facilitated the identification of all those specimens. As a result, eleven species, including five newly discovered ones named Gy. gyirongensis, Gy. variisporus, Gy. tomentosiceps, Gy. tenuibasidialis, and Gy. aurantipileatus, were recognized. Significantly, four of the five newly identified species are native to the Xizang Autonomous Region, emphasizing their specialization in this distinctive habitat. This research contributes to our comprehension of Gymnopilus diversity and lays the groundwork for the conservation and sustainable utilization of Gymnopilus resources.

Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer.

Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.

Research on the Interaction Mechanism and Structural Changes in Human Serum Albumin with Hispidin Using Spectroscopy and Molecular Docking.

The interaction between human serum albumin (HSA) and hispidin, a polyketide abundantly present in both edible and therapeutic mushrooms, was explored through multispectral methods, hydrophobic probe assays, location competition trials, and molecular docking simulations. The results of fluorescence quenching analysis showed that hispidin quenched the fluorescence of HSA by binding to it via a static mechanism. The binding of hispidin and HSA was validated further by synchronous fluorescence, three-dimensional fluorescence, and UV/vis spectroscopy analysis. The apparent binding constant (Ka) at different temperatures, the binding site number (n), the quenching constants (Ksv), the dimolecular quenching rate constants (Kq), and the thermodynamic parameters (∆G, ∆H, and ∆S) were calculated. Among these parameters, ∆H and ∆S were determined to be 98.75 kJ/mol and 426.29 J/(mol·K), respectively, both exhibiting positive values. This observation suggested a predominant contribution of hydrophobic forces in the interaction between hispidin and HSA. By employing detergents (SDS and urea) and hydrophobic probes (ANS), it became feasible to quantify alterations in Ka and surface hydrophobicity, respectively. These measurements confirmed the pivotal role of hydrophobic forces in steering the interaction between hispidin and HSA. Site competition experiments showed that there was an interaction between hispidin and HSA molecules at site I, which situates the IIA domains of HSA, which was further confirmed by the molecular docking simulation.