Identification and prognostic analysis of metabolic genes associated with TP53 mutation in multiple myeloma.

BACKGROUND: TP53 gene mutation is crucial in determining the prognosis of Multiple Myeloma (MM) patients. Understanding metabolic genes linked to TP53 mutation is vital for developing targeted therapies for these patients. METHOD: We analyzed The Cancer Genome Atlas (TCGA) dataset to identify genes related to TP53 mutation and metabolism. Using univariate Cox regression and protein-protein interaction (PPI) analysis, we identified key genes. We categorized patients into high and low metabolism groups via non-negative matrix factorization (NMF) clustering, which led to the discovery of relevant differential genes. Integrating these with genes from the Gene Expression Omnibus (GEO) datasets and PPI interactions, we pinpointed crucial metabolic genes associated with TP53 mutation in MM. Additionally, we conducted prognostic analyses involving survival curves and receiver operating characteristic (ROC) charts. RESULTS: Our study reveals that the metabolic gene ribonucleotide reductase M2 (RRM2), linked to TP53 mutation, correlates positively with the International Staging System (ISS) stage in MM patients and is an independent prognostic risk factor. In the TCGA dataset, among the 767 patients, the 35 MM patients with TP53 mutation generally had poor survival outcomes. Specifically, the patients with both TP53 mutation and high RRM2 expression had a 2-year survival rate of only 38.87%, whereas those with normal TP53 function and low RRM2 expression had a 2-year survival rate of 86.31% (p < 0.001). CONCLUSION: RRM2 significantly impacts MM prognosis and is associated with TP53 mutation, presenting itself as a potential therapeutic target and prognostic marker for MM.

Superhydrophilic PANI/Ag/TA@PVDF Composite Membrane with Antifouling Property for Oil-Water Separation.

The current membrane materials used for oil-water separation suffer from low separation efficiency and poor durability, and membrane contamination is also a key issue that must be addressed urgently. In this paper, a superhydrophilic PANI/Ag/TA@PVDF composite membrane with PANI-Ag NPs heterojunction structure was prepared via chelation and reduction of Ag+ by tannic acid (TA) and in situ growth of hydrochloric acid-doped polyaniline (PANI). TA endows the prepared composite membrane with excellent superhydrophilicity and underwater oleophobicity, remarkable oil-water separation capacity (the separation efficiency of more than 97% for soybean oil), and extraordinary antifouling properties. Notably, the range of photodegradation is expanded from UV to visible light by the construction of a Schottky heterostructure between PANI and Ag NPs, the photocatalytic degradation ability of composite membrane for organic pollutants has been improved obviously, and the degradation efficiency for crystal violet (CV) is 97.9%. Considering these merits, the PANI/Ag/TA@PVDF composite membrane provides an effective strategy to overcome the shortcomings of existing membrane materials, presenting enormous potential in the treatment and purification of oily wastewater.

TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study.

BACKGROUND: The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM: To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS: This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS: The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION: The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

A solid-state pulse power sub-nanosecond SiC DSRD-based generator with high-voltage and high repetition frequency for pulse discharge water treatment.

Water treatment is one of the most important issues for all walks of life around the world. The unique advantages of the solid-state power electronic pulses in water treatment make it attractive and promising in practical applications. The output voltage, rising time, repetition rate, and peak power of output pulses have a significant impact on the effectiveness of water treatment. Especially in pulse electric field treatment and pulse discharge treatment, the pulse with fast rising time achieves the advantage of generating plasma without corona, which can avoid water heating effect and greatly improve the efficiency of the pulse generator. High repetition rate can significantly reduce the peak power requirement of the pulse in water treatment application, making the equipment smaller and improving the power density. Therefore, the study developed a high-voltage high frequency sub-nanosecond pulse power generator (PPG) system for wastewater treatment. It adopts SiC DSRD (Drift Step Recovery Diode) solid-state switches and realize modular design, which can achieve high performance and can be flexible expanded according to the requirements of water treatment capacity. Finally, an expandable high-voltage PPG for water treatment is built. The output parameters of the PPG include output pulse voltage range from 1 to 5.28 kV, rise time <600 ps (20%-90%), repetition up to 1 MHz. The experiment results of PPG application for pulse discharge water treatment is presented. The results indicate that the proposed generator achieves high-efficiency degradation of 4-Chlorophenol (4-CP), which is one of the most common chlorophenol compounds in wastewater. From experiment, the homemade system can degrade 450 mL waste water containing 500 mg/L 4-CP in 35 min, with a degradation rate of 98%. Thereby, the requirement for electric field intensity decreased. Through the further quantitative analysis, the impact of frequency, voltage, and electrode spacing on the degradation effect of 4-CP is confirmed.

Immunohistochemical and molecular profiles of heterogeneous components of metaplastic breast cancer: a squamous cell carcinomatous component was distinct from a spindle cell carcinomatous component.

Metaplastic breast carcinoma (MBC), a category of breast cancer, includes different histological types, which are occasionally mixed and heterogeneous. Considering the heterogeneity of cancer cells in a tumour mass has become highly significant, not only from a biological aspect but also for clinical management of recurrence. This study aimed to analyse the immunohistochemical and molecular profiles of each MBC component of a tumour mass. Twenty-five MBC tumours were histologically evaluated, and the most frequent MBC component (c) was squamous cell carcinoma (SCC), followed by spindle cell carcinoma (SpCC). A total of 69 components of MBC and non-MBC in formalin-fixed paraffin-embedded sections were examined for 7 markers by immunohistochemistry. SCC(c) were significantly PTEN negative and CK14 positive, and SpCC(c) were significantly E-cadherin negative and vimentin positive. Multivariate analyses revealed that immunohistochemical profiles of normal/intraductal (IC)(c), no special type (NST)(c), and MBC(c) differed; moreover, SCC(c) and SpCC(c) were distinctly grouped. PTEN gene mutation was detected only in SCC(c) (2/7), but not in SpCC(c). Next-generation sequence analyses for 2 cases with tumours containing SCC(c) demonstrated that PTEN gene mutation increased progressively from IC(c) to NST(c) to SCC(c). In conclusion, the immunohistochemical and molecular profiles of the SCC(c) of MBC are distinct from those of the SpCC(c).

The impact of long-term antihypertensive treatment on wound healing after major non-cardiac surgery in patients with cardiovascular diseases: A meta-analysis.

Hypertension is a prevalent condition that poses significant challenges in the perioperative management of patients undergoing major non-cardiac surgery, particularly concerning wound healing and scar formation. This meta-analysis assesses the impact of long-term antihypertensive treatment on postoperative wound healing, examining data from seven studies involving patients who received such treatments compared to untreated controls. Our findings reveal that long-term antihypertensive therapy is associated with significantly improved wound healing outcomes, as indicated by lower REEDA scores (I2 = 96%, SMD = -25.71, 95% CI: [-33.71, -17.70], p < 0.01) 1 week post-surgery and reduced scar formation, demonstrated by lower Manchester Scar Scale scores (I2 = 93%, SMD = -37.29, 95% CI: [-44.93, -29.64], p < 0.01) 2 months post-surgery. These results underscore the potential benefits of antihypertensive treatment in enhancing surgical recovery and offer insights into optimising perioperative care for hypertensive patients.

Schwann cells in pancreatic cancer: Unraveling their multifaceted roles in tumorigenesis and neural interactions.

Pancreatic ductal adenocarcinoma (PDAC), characterized by heightened neural density, presents a challenging prognosis primarily due to perineural invasion. Recognized for their crucial roles in neural support and myelination, Schwann cells (SCs) significantly influence the process of tumorigenesis. This review succinctly outlines the interplay between PDAC and neural systems, positioning SCs as a nexus in the tumor-neural interface. Subsequently, it delves into the cellular origin and influencers of SCs within the pancreatic tumor microenvironment, emphasizing their multifaceted roles in tumor initiation, progression, and modulation of the neural and immune microenvironment. The discussion encompasses potential therapeutic interventions targeting SCs. Lastly, the review underscores pressing issues, advocating for sustained exploration into the diverse contributions of SCs within the intricate landscape of PDAC, with the aim of enhancing our understanding of their involvement in this complex malignancy.

Integrated morphological, physiological and transcriptomic analyses reveal response mechanisms of rice under different cadmium exposure routes.

Rice (Oryza sativa) is one of the major cereal crops and takes up cadmium (Cd) more readily than other crops. Understanding the mechanism of Cd uptake and defense in rice can help us avoid Cd in the food chain. However, studies comparing Cd uptake, toxicity, and detoxification mechanisms of leaf and root Cd exposure at the morphological, physiological, and transcriptional levels are still lacking. Therefore, experiments were conducted in this study and found that root Cd exposure resulted in more severe oxidative and photosynthetic damage, lower plant biomass, higher Cd accumulation, and transcriptional changes in rice than leaf Cd exposure. The activation of phenylpropanoids biosynthesis in both root and leaf tissues under different Cd exposure routes suggests that increased lignin is the response mechanism of rice under Cd stress. Moreover, the roots of rice are more sensitive to Cd stress and their adaptation responses are more pronounced than those of leaves. Quantitative PCR revealed that OsPOX, OsCAD, OsPAL and OsCCR play important roles in the response to Cd stress, which further emphasize the importance of lignin. Therefore, this study provides theoretical evidence for future chemical and genetic regulation of lignin biosynthesis in crop plants to reduce Cd accumulation.

Radiological classification of the Heidelberg triangle and its application in laparoscopic pancreaticoduodenectomy for malignancies.

BACKGROUND: The TRIANGLE operation benefits patients with pancreatic cancer; however, the Heidelberg triangle, where the operation occurs, contains vessels that can impact safety, especially in laparoscopic pancreaticoduodenectomy (LPD) with the TRIANGLE operation. This study aimed to identify Heidelberg triangle vessel types and their implications in pancreaticoduodenectomy (PD). METHODS: Retrospective collection of radiographic data was performed from January 2017 to April 2023. Three-dimensional (3D) CT reconstructions were performed on patients. Vascular types in the Heidelberg triangle were classified based on named vessels crossing its interior. The impact of these types on surgical outcomes and complications in PD with the TRIANGLE operation was assessed. RESULTS: Preoperative CT reconstruction was conducted on 184 pancreatic surgery patients. The findings revealed 99 patients (53.8%) with the type I Heidelberg triangle, lacking named vessels crossing the interior. Type II (n = 85, 46.2%), with named vessels crossing the interior, was identified. Among reconstructed patients who underwent PD with the TRIANGLE operation (n = 103), they were categorized as type I (n = 57) or type II (n = 46). The results showed that LPD patients with type II had significantly higher median intraoperative blood loss (300 mL vs. 200 mL, P = 0.030) and mean examined lymph nodes (17.2 ± 7.6 vs. 13.4 ± 5.2, P = 0.019) compared to those with type I. No significant differences were found in operative time or postoperative complications. CONCLUSION: The presence of named vessels crossing the interior of the Heidelberg triangle was associated with increased intraoperative bleeding during LPD combined with the TRIANGLE operation. Therefore, targeted preoperative planning is required before the operation, thus improving the safety of the TRIANGLE operation in minimally invasive surgery.

Phenotype of Takayasu-like vasculitis and cardiopathy in patients with Blau syndrome.

OBJECTIVES: We aimed to determine the prevalence of cardiovascular involvement in our Blau syndrome (BS) cohort and provide detailed analysis of their cardiovascular manifestations and outcome. We also tried to find out the risk factors for developing cardiovascular involvement. METHODS: Clinical manifestations, laboratory findings, and treatments were reviewed. Clinical features were compared between children with cardiovascular involvement and those without angiocardiopathy. RESULTS: A total of 38 BS children were eligible for final analysis. Among them, 13 (34.2%) developed Takayasu-like vasculitis and/or cardiopathy. Compared with those without angiocardiopathy, recurrent fever was more frequent in BS patients with cardiovascular involvement (p < 0.001). What is more, tumor necrosis factor alpha antagonists (anti-TNF) were more urgently needed in children with cardiovascular involvement (p = 0.015). BS patients with cardiovascular involvement include 4 with Takayasu-like vasculitis and 9 with cardiopathy. The onset of cardiovascular manifestations ranged from 0.75 to 18.5 years of age, with most cases occurring before school period. Symptoms were elusive and lacked specificity, such as dizziness, short of breath, and edema. Some patients were even identified because of the unexpected hypertension during follow-up. Cardiopathy and vasculitis occurred in patients with different genotypes. Imaging changes were discovered before the presentation of the typical triad in 3/4 patients with Takayasu-like vasculitis. Three children developed left ventricular dysfunction with decreased left ventricular ejection fraction. Combination of glucocorticoids and methotrexate with anti-TNF agents is a common treatment option for these BS patients. In the cohort, BS-related cardiovascular involvement was controlled well, with cardiac structural and functional abnormalities completely recovered and slower progression of vasculitis lesions. CONCLUSION: Cardiovascular manifestations is not rare in BS patients. Because of its insidious onset, a systematic and comprehensive assessment of cardiovascular involvement should be performed in newly diagnosed patients with BS. Aggressive initiation of anti-TNF agents may be beneficial to improve the prognosis. Key Points • About 34.2% patients with Blau syndrome developed Takayasu-like vasculitis and/or cardiopathy. • Compared with those without angiocardiopathy, recurrent fever and application of anti-TNF agents were more frequent in BS patients with cardiovascular involvement (p < 0.001, p = 0.015) • Regular assessment of cardiovascular involvement is extremely necessary because of its insidious onset.

Different effects of crizotinib treatment in two non-small cell lung cancer patients with SDC4::ROS1 fusion variants.

The possibility of stratifying patients according to differences in ROS proto-oncogene 1 (ROS1) fusion partners has been discussed. This study aimed to clarify the clinicopathological differences between two SDC4::ROS1 positive NSCLC cases who had different responses to crizotinib. Cytology and pathology samples from two NSCLC cases with SDC4::ROS1 who were diagnosed and treated with crizotinib at Nihon University Itabashi Hospital were obtained. Case 1 has been well-controlled with crizotinib for over 5 years, but case 2 was worse and overall survival was 19 months. Sequencing analysis of ROS1 fusion genes was performed by reverse-transcription-PCR and Sanger's sequencing methods. In addition, thyroid transcription factor (TTF)-1, ROS-1, Ki67, and phosphorylated extracellular signal-regulated kinase (pERK)1/2 expression were investigated using immunohistochemistry. Sequencing analysis showed SDC4 exon2::ROS1 exon 32 (exon33 deleted) in case 1, and coexistence of SDC4 exon2::ROS1 exon 34 and SDC4 exon2::ROS1 exon35 in case 2. The Ki67 index was not different, but ROS1 and pERK1/2 expression levels tended to be higher in the tumor cells of case 2 than in case 1. Therapeutic response to crizotinib and patients' prognosis in ROS1 rearranged NSCLC may be related to the activation of ROS1 signaling, depending on ROS1 and pERK1/2 overexpression status, even if the ROS1 fusion partner is the same.

Selected pesticidal POPs and metabolites in the soil of five Vietnamese cities: Sources, fate, and health risk implications.

Large quantities of organochlorine pesticides (OCPs) have been used in tropical regions. The fate processes and risks of these legacy contaminants in the tropics are poorly understood. Herein, we investigated the occurrence of three classes of widely used OCPs and their metabolites in surface and core soil from five cities across Vietnam with a prevalent tropical monsoon climate and a long history of OCP application. We aimed to elucidate migration potentials, degradation conditions, and transformation pathways and assess current health risks of these contaminants. Generally, the concentrations of OCPs and metabolites in the soil core were slightly lower than those in surface soil except for hexachlorocyclohexane (HCH) isomers. 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), the sum of dicofol and 4,4'-dichlorobenzophenone (p,p'-DBP), and 2,2-bis(4-chlorophenyl)-1,1-dichloroethane (p,p'-DDD) were the most abundant compounds in both surface and core soils. A uniform distribution of HCHs (the sum of α-, ß-, γ-, and δ-HCH) at trace levels was found in almost all soils, serving as evidence of the lack of recent use of HCH pesticides. Higher concentrations of DDTs (the sum of DDT, DDD, and DDE) were observed in north-central Vietnamese soil, whereas appreciable concentrations of ENDs (the sum of α- and ß-endosulfan and endosulfan sulfate) were only found in southern Vietnamese soils. Empirical diagnostic ratios indicated residuals of DDTs were mainly from technical DDT rather than dicofol, whereas aged HCHs could be explained by the mixture of lindane and technical HCH. Both historical applications and recent input explain DDTs and ENDs in Vietnamese soil. Total organic carbon performs well in preventing vertical migration of more hydrophobic DDTs and ENDs. The dominant transformation pathway of DDT in surface soil followed p,p'-DDE→2,2-bis(4-chlorophenyl)-1-chloroethylene or p,p'-DDMU→1,1-bis(4-chlorophenyl)ethylene or p,p'-DDNU→p,p'-DBP, whereas the amount of p,p'-DDMU converted from p,p'-DDD and p,p'-DDE is similar in soil core. Non-cancer risks of OCPs and metabolites in all soils and cancer risks of those chemicals in core soils were below the safety threshold, whereas a small proportion of surface soil exhibited potential cancer risk after considering the exposure pathway of vegetable intake. This study implied that organic matter in non-rainforest tropical deep soils still could hinder the leaching of hydrophobic organic contaminants as in subtropical and temperate soils. When lands with a history of OCP application are used for agricultural purposes, dietary-related risks need to be carefully assessed.

A long-term retrospective analysis of management of cervical cancer during pregnancy.

OBJECTIVE: This study aims to describe cervical cancer during pregnancy (CCP) and investigate factors associated with survival outcomes. METHODS: This retrospective matched study included CCP patients from May 2007 to August 2021 and matched non-pregnant cervical cancer patients (1:2) based on age (±5 years), year at diagnosis (±2 years), histological type and stage (2018 FIGO). The Kaplan-Meier method and multivariate Cox regression analyses were used to assess the impact of pregnancy and clinicopathologic factors on prognosis. RESULTS: Thirty-eight CCP patients (stage IA to IIIC) and 76 non-pregnant patients were included. Most CCP patients were diagnosed in the first (31.6%) or second (47.4%) trimester. CCP patients had a longer waiting time than non-pregnant patients. Pregnancy continued in 42.1% (continuation of pregnancy [COP] group) and was terminated in 57.9% (termination of pregnancy [TOP] group) of patients. Survival analysis showed no significant differences in recurrence-free survival (RFS) or overall survival (OS) between pregnant and non-pregnant patients or between the COP and TOP groups. At the end of the follow-up period (range 12-178 months), 23 children born to CCP patients exhibited normal development. CONCLUSION: Pregnancy does not impact cervical cancer prognosis. The oncologic outcomes of the TOP and COP groups were comparable. A pregnancy-preserving strategy could be considered for managing CCP patients.

Association between cigarette smoking and serum alpha klotho levels among US adults over 40-years-old: a cross-sectional study.

Alpha klotho (α-Klotho) is an anti-aging molecule associated with aging and several diseases. Previous studies have reported inconsistent levels of α-Klotho in smokers. This study aimed to demonstrate serum α-Klotho levels in smokers among the US population. This cross-sectional study recruited 11,559 participants (aged 40-79 years; 48.2% males). All data were collected from the 2007-2016 National Health and Nutrition Examination Survey. The study comprised adults with reliable Klotho and smoking questionnaire results. The relationship between smoking and serum α-klotho levels was assessed using multivariate linear regression models after adjusting for potential confounders. We also performed a stratified analysis of clinically important variables. The mean serum α-klotho level among the 11,559 participants was 843.85 pg/mL. After full adjustment, habitual smoking was significantly associated with decreased serum levels of α-klotho level (ß = - 34.89; 95% CI - 54.97, - 14.81; P = 0.0013) in the total study population. Furthermore, the stratified analysis indicated that the association was insignificant in the 60-79 age group. Quitting smoking was not significantly associated with serum levels of α-klotho as expected (P = 0.1148) in the total study population. However, stratified analyses showed a significant inversed association in the male, those with chronic kidney disease, or those with cancer who quit smoking (all P < 0.05). Cigarette smoking was inversely associated with serum α-Klotho levels among US adults.

Comparison of the survival outcomes of laparoscopic, abdominal and gasless laparoscopic radical hysterectomy for early-stage cervical cancer: trial protocol of a multicenter randomized controlled trial (LAGCC trial).

Background: Radical hysterectomy (RH) is considered a cornerstone in the treatment of early-stage cervical cancer. However, the debate surrounding the optimal surgical approach, whether minimally invasive or open surgery, remains controversial. The objective of this trial is to evaluate the survival outcomes of cervical cancer patients who undergo different surgical approaches. Methods: This study is designed as a prospective, multicenter, open, parallel, and randomized controlled trial. A total of 500 patients diagnosed with stage IA1 with LVSI, IA2, IB1, or IB2 (2018 FIGO) will be recruited. Recruitment of participants started in November 2020. The participants will be randomly assigned to one of three groups: conventional laparoscopic RH, gasless laparoscopic RH, or abdominal RH. The primary endpoint of this trial is the 2-year disease-free survival (DFS) rate. The secondary endpoints will include the 2-year overall survival (OS) rate, 5-year DFS/OS, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and impact on quality of life (QoL). Discussion: We expect this trial to provide compelling and high-quality evidence to guide the selection of the most appropriate surgical approach for early-stage cervical cancer. Clinical trial registration: Chinese Clinical Trial Register, identifier ChiCTR2000035515.

Association between daily alcohol consumption and serum alpha klotho levels among U.S. adults over 40 years old: a cross-sectional study.

BACKGROUND: Klotho is a hormone considered to be an anti-aging biomarker. The relationships between daily alcohol consumption and serum klotho are mainly unknown. The purpose of this study is to assess the relationship between alcohol consumption and serum alpha klotho (α-klotho) levels in the U.S. METHODS: The data came from 11,558 participants aged ≥ 40 in the 2007-2016 National Health and Nutrition Examination Survey. Adults with reliable α-klotho plasma results were the target population. The self-report method was used to assess alcohol consumption. The relationship between daily alcohol intake and serum α-klotho levels was estimated using multivariable linear regression models. We also performed a stratified analysis of clinically important variables. RESULTS: The mean serum α-klotho level among the 11,558 participants was 843.82 pg/mL. After full adjustment, participants with current moderate and heavy alcohol intake had lower serum α-klotho levels than those who never alcohol intake (ß = - 62.64; 95% CI: - 88.86, - 36.43; P < 0.001; ß = - 81.54; 95% CI: - 111.54, - 51.54; P < 0.001, respectively). Furthermore, the stratified analysis indicated that the association was insignificant in individuals with cardiovascular disease, chronic kidney disease, or cancer. CONCLUSION: Daily alcohol consumption was inversely associated with serum α-klotho levels among U.S. adults over 40 years old. However, individuals with cardiovascular disease, chronic kidney disease, or cancer found no such relationship.

GSH-activatable camptothecin prodrug-loaded gold nanostars coated with hyaluronic acid for targeted breast cancer therapy via multiple radiosensitization strategies.

Breast cancer has overtaken lung cancer to rank as the top malignant tumor in terms of incidence. Herein, a gold nanostar (denoted as AuNS) is used for loading disulfide-coupled camptothecin-fluorophore prodrugs (denoted as CPT-SS-FL) to form a nanocomposite of AuNS@CPT-SS-FL (denoted as AS), which, in turn, is further encapsulated with hyaluronic acid (HA) to give the final nanoplatform of AuNS@CPT-SS-FL@HA (denoted as ASH). ASH effectively carries the prodrug and targets the CD44 receptor on the surface of tumor cells. The endogenously overexpressed glutathione (GSH) in tumor cells breaks the disulfide bond to activate the prodrug and release the radiosensitizer drug camptothecin (CPT) and the fluorescence imaging reagent rhodamine derivative as a fluorophore (FL). The released FL can track the precise release position of the radiosensitizer camptothecin in tumor cells in real time. The AuNS has strong X-ray absorption and deposition ability due to the high atomic coefficient of elemental Au (Z = 79). At the same time, the AuNS can alleviate the tumor microenvironment (TME) hypoxia through its mild photothermal therapy (PTT). Therefore, through the multiple radiosensitizing effects of GSH depletion, the high atomic coefficient of Au, and hypoxia alleviation, accompanied by the radiosensitizer camptothecin, the designed ASH nanoplatform can effectively induce strong immunogenic cell death (ICD) at the tumor site via radiosensitizing therapy combined with PTT. This work provides a new way of constructing a structurally compact and highly functionalized hierarchical system toward efficient breast cancer treatment through ameliorating the TME with multiple modalities.

Immunogenic Radiation Therapy for Enhanced Antitumor Immunity via a Core-Shell Nanosensitizer-Mediated Immunosuppressive Tumor Microenvironment Modulation.

Due to the immunosuppressive tumor microenvironment (TME) and weak radiation absorption, the immune response triggered by radiation therapy (RT) is limited. Herein, a core-shell nanosensitizer UiO@MnS (denoted as UM) was genuinely constructed for the amplification of RT efficacy and induction of immunogenicity via integrating MnS-reprogrammed TME with Hf-based UiO-sensitized RT. The acid-sensitive MnS would produce H2S under acidic TME to improve oxygenation through inhibition mitochondrial respiration and reducing metabolic oxygen consumption, leading to decreased HIF-1α expression and enhanced radiosensitization. In addition, the generated H2S inhibited the catalase activity to increase the H2O2 level, which subsequently enhanced the Mn2+-mediated Fenton-like reaction, resulting in G2/M cell cycle arrest to improve the cellular sensitivity for radiation. This impressive tumor oxygenation, cell cycle arrest, and radiosensitization procedure boosted RT efficacy and resulted in strong antitumor immunogenicity. Taken together, combining the immunosuppressive TME modulation with a sensitizing radiation strategy shows great promise for magnifying immunogenic RT outputs.

Preparation and Characterization of a One-Step Electrospun Poly(Lactic Acid)/Wormwood Oil Antibacterial Nanofiber Membrane.

With the continuous improvement of the standard of living, people are increasingly inclined towards natural, green, and environmentally friendly products. Plant-based products that are safe, natural, non-toxic, and beneficial to human health are often more favored. Poly(lactic acid) (PLA) is a polymer obtained through lactate polymerization using renewable plant resources such as corn and has excellent biocompatibility and biodegradability. It is widely used in the field of food packaging. Wormwood oil (WO) is an oil extracted from the stems and leaves of Artemisia plants, and it has broad-spectrum antibacterial properties. In this article, through electrospinning technology, wormwood oil was directly incorporated into PLA, giving the PLA nanofiber membrane antioxidant and antibacterial functions. Various parameters such as voltage (11 KV, 13 KV, 15 KV), spinning solution concentration (8%, 10%, 12%), distance (15 cm, 17 cm, 19 cm), and feeding rate (0.4 mL/h, 0.5 mL/h, 0.6 mL/h) were explored, and the resulting spun fibers were characterized. Through SEM characterization, it was found that when the spinning voltage was 13 KV, the spinning solution concentration was 10%, the distance was 17 cm, and the feeding rate was 0.5 mL/h, the nanofiber membrane had a smooth morphology without bead formation, with an average diameter of 260 nm. The nanofiber membrane was characterized using FTIR, TG, and SEM, confirming the successful incorporation of artemisia essential oil into PLA. The prepared antimicrobial nanofilm was subjected to antimicrobial testing, and the results showed that as the concentration of the essential oil increased, the inhibition zones also increased. When wormwood oil concentration was 4%, the diameter of the inhibition zone for Staphylococcus aureus increased from 1.0 mm to 3.5 mm, while the diameter of the inhibition zone for Escherichia coli increased from 2.0 mm to 4.5 mm.

Repeated Surgery in a Case of Epithelial-Myoepithelial Carcinoma of the Parotid Gland that was Difficult to Distinguish from Pleomorphic Adenoma.

Epithelial-myoepithelial carcinoma (EMC) of the parotid gland is a comparatively rare tumor that accounts for less than 1% of all salivary gland tumors. A patient with EMC of the parotid gland that was initially diagnosed as pleomorphic adenoma and that recurred locally during the watchful waiting period but was controlled by surgery under local anesthesia is reported. An 80-year-old man had noticed a swelling in the left infra aural region. A left parotid gland tumor was suspected, and he was referred to our department. Magnetic resonance imaging (MRI) and fine-needle aspiration cytology findings were suggestive of pleomorphic adenoma of the superficial lobe of the parotid gland, and this was therefore resected under general anesthesia. Postoperative histopathological examination, immunostaining, and genetic tests resulted in a diagnosis of EMC. Postoperative pathological review showed that part of the resection margin was positive. The possibility of recurrence was explained to the patient, and additional treatment was recommended, but since the patient did not desire this, a policy of watchful waiting was adopted. Signs of cutaneous metastasis in the left infra aural region were detected at 13 months postoperatively, and this metastasis was excised under local anesthesia. The resection margin was negative, and the patient's course remains uneventful. EMC is classified as a low-grade malignant tumor, but it requires stringent monitoring because of its frequent local recurrence. Since local control can usually be achieved by surgical treatment alone, and postoperative adjuvant therapy may not necessarily warranted.