Induction chemotherapy regimes in first-line treatment for locoregionally advanced nasopharyngeal carcinoma: A network meta-analysis and cost-effectiveness analysis.

OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.

Toward the Next Generation Human-Machine Interaction: Headworn Wearable Devices.

Wearable devices are lightweight and portable devices worn directly on the body or integrated into the user's clothing or accessories. They are usually connected to the Internet and combined with various software applications to monitor the user's physical conditions. The latest research shows that wearable head devices, particularly those incorporating microfluidic technology, enable the monitoring of bodily fluids and physiological states. Here, we summarize the main forms, functions, and applications of head wearable devices through innovative researches in recent years. The main functions of wearable head devices are sensor monitoring, diagnosis, and even therapeutic interventions. Through this application, real-time monitoring of human physiological conditions and noninvasive treatment can be realized. Furthermore, microfluidics can realize real-time monitoring of body fluids and skin interstitial fluid, which is highly significant in medical diagnosis and has broad medical application prospects. However, despite the progress made, significant challenges persist in the integration of microfluidics into wearable devices at the current technological level. Herein, we focus on summarizing the cutting-edge applications of microfluidic contact lenses and offer insights into the burgeoning intersection between microfluidics and head-worn wearables, providing a glimpse into their future prospects.

The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. METHOD: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. RESULT: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034). CONCLUSIONS: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

Preliminary Screening and Study of Key Gene Expression in Endometrial Window Period.

Background: Implantation is a highly coordinated event involving both embryonic and endometrial participation. The endometrium expresses a complex array of proteins during the menstrual cycle many of which help to define a period of receptivity collectively known as the "window of implantation." Objective: Using high-throughput RNA sequencing technology analysis to find differentially expressed genes before and after the endometrial window, and search for key marker genes of the membrane implantation window. Design: This was a retrospective study. Setting: This study was performed in the Department of Obstetrics and Gynecology, Taizhou People's Hospital. Participants: Fifty patients with repeated implantation failure in in vitro fertilization were selected and were divided into (1) the normal window group (36 cases); (2) the window forward group (8 cases); and (3) the window backward group (6 cases) based on endometrial biopsy findings. Interventions: Using RNA sequencing technology combined with biological information analysis tools to analyze the differentially-expressed genes in 9 samples. Gene Ontology databases were used for the functional annotation of these differentially-expressed genes. Kyoto Encyclopedia of Genes and Genomes analysis was used to draw a signal path diagram. Primary Outcome Measures: (1) Screening of differentially-expressed genes and (2) functional analysis of the differential genes. Results: A total of 22 differentially-expressed genes related to endometrial receptivity were obtained by transcriptome sequencing. Seven of the 22 differentially-expressed genes have been shown to have a close relationship with the endometrial receptive window period. Further, it was proved that the Wnt signaling pathway and mitogen-activated protein kinase signaling pathway were closely related to endometrial receptivity. Conclusions: The present study identified a series of key genes and pathways that may be involved in the endometrial window period, providing an experimental and theoretical basis for exploring the personalized embryo transfer program.

A Nomogram to Predict Anal Condyloma Acuminatum Recurrence in HIV-negative Patients Following Photodynamic Therapy: A Decade-Long Retrospective Clinical Study at a Single Tertiary Hospital.

BACKGROUND: Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates significant efficacy and safety in treating anal CA, it does not completely prevent recurrence. This study aimed to develop and validate a nomogram model in predicting the risk of relapse in HIV-negative patients with anal CA following treatment with ALA-PDT. METHODS: A retrospective analysis was conducted on patients diagnosed with anal CA who received combined CO2 laser vaporization and ALA-PDT between January 2013 and May 2023. Patients were divided into recurrence and non-recurrence groups. A nomogram was developed based on factors showing statistical significance in multivariable logistic regression analysis. The discriminative ability and clinical utility of the nomogram were assessed via ROC curves and decision curve analysis, with internal validation performed through bootstrap resampling. RESULTS: Among the 176 patients included, 33 (18.75%) experienced recurrence, while 143 did not. Independent predictors for recurrence included HPV types, history of anal intercourse, and the number of CO2 laser treatments received. Incorporating these predictors, the nomogram demonstrated a superior diagnostic performance (area under the curve = 0.881, 95% CI: 0.818-0.935) and a significant net benefit in decision curve analysis. CONCLUSIONS: The nomogram accurately predicts the risk of recurrence in HIV-negative patients with anal CA following ALA-PDT. It offers a valuable tool for guiding preoperative clinical decision-making and establishing personalized treatment strategies to minimize the risk of relapse.

Identification and validation of a prognostic signature based on six immune-related genes for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy with high mortality and morbidity rates. Although the significant efficacy of immunotherapy is well established, it is only beneficial for a limited number of individuals with CRC. METHODS: Differentially expressed immune-related genes (DE-IRGs) were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ImmPort databases. A prognostic signature comprising DE-IRGs was developed using univariate, LASSO, and multivariate Cox regression analyses. A nomogram integrating the independent prognostic factors was also developed. CIBERSORT was used to assess immune cell infiltration (ICI). Furthermore, wound-healing, colony formation, migration, and invasion assays were performed to study the involvement of ACTG1 in CRC. RESULTS: A signature including six DE-IRGs was developed. The overall survival (OS) rate was accurately estimated for TCGA and GSE38832 cohorts. The risk score (RS) of the signature was an independent factor for OS. Moreover, a nomogram encompassing age, RS, and pathological T stage accurately predicted the long-term OS probability of individuals with CRC. The high-risk group had an elevated proportion of patients treated with ICIs, including native B cells, relative to the low-risk group. Additionally, ACTG1 expression was upregulated, which supported the proliferation, migration, and invasion abilities of CRC cells. CONCLUSIONS: An immune-related prognostic signature was developed for predicting OS and for determining the immune status of individuals with CRC. The present study provides new insights into accurate immunotherapy for individuals with CRC. Moreover, ACTG1 may serve as a new immune biomarker.

Correction: Cell Therapy: A Safe and Efficacious Therapeutic Treatment for Alzheimer's Disease in APP+PS1 Mice.

[This corrects the article DOI: 10.1371/journal.pone.0049468.].

A Network Meta-Analysis of the Systemic Therapies in Unresectable Head and Neck Squamous Cell Carcinoma.

The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. METHODS: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. RESULTS: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. CONCLUSION: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.

The current standard treatment for advanced head and neck cancer involves combining radiation therapy with chemotherapy. However, there are ongoing trials exploring alternative therapies. In this study, we conducted a comprehensive analysis of existing treatments using a statistical method called network meta-analysis. Our analysis included data from randomized controlled trials published between January 2000 and July 2023. We focused on overall survival and progression-free survival as key outcome measures. The results of our analysis showed that none of the alternative treatments demonstrated significant advantages over the standard concurrent chemoradiotherapy. Nevertheless, there is potential for improved outcomes when targeted therapy or induction chemotherapy is combined with concurrent chemoradiotherapy.

Association between hypertensive disorders and Bell's palsy in pregnancy: protocol for a systematic review and meta-analysis.

BACKGROUND: Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. Pregnancy, diabetes mellitus and hypertension are the risk factors for Bell's palsy. However, the association between hypertensive disorders and Bell's palsy during pregnancy or the puerperium remains unclear. This systematic review will comprehensively summarise the literature and evaluate the association between Bell's palsy and hypertensive disorders during pregnancy or the puerperium. METHODS AND ANALYSIS: Systematic searches of PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be undertaken using prespecified search strategies. Observational studies (cross-sectional studies, cohort studies, case reports and series case reports) written in English that investigate the association between hypertensive disorders of late pregnancy and Bell's palsy during pregnancy or the puerperium will be included. Different authors will independently conduct the eligible study selection, perform data extraction and appraise the quality of included studies. Subgroup analysis will be carried out based on the age of pregnant women (≤35 years old, >35 years old), parity (primipara, multipara) and fetus number (singleton or multiple-gestation pregnancy). ETHICS AND DISSEMINATION: This review will be based on published literature, and thus there is no requirement for ethics approval. The results of this study will aid in the knowledge of the relationship between Bell's palsy during pregnancy or the puerperium and hypertensive disorders of late pregnancy. The results of this systematic review will be shared through publication in a peer-reviewed journal with good visibility for the field of obstetrics and presentations at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023422902.

Biocompatible Copper-Based Nanocomposites for Combined Cancer Therapy.

Copper (Cu) and Cu-based nanomaterials have received tremendous attention in recent years because of their unique physicochemical properties and good biocompatibility in the treatment of various diseases, especially cancer. To date, researchers have designed and fabricated a variety of integrated Cu-based nanocomplexes with distinctive nanostructures and applied them in cancer therapy, mainly including chemotherapy, radiotherapy (RT), photothermal therapy (PTT), chemodynamic therapy (CDT), photodynamic therapy (PDT), cuproptosis-mediated therapy, etc. Due to the limited effect of a single treatment method, the development of composite diagnostic nanosystems that integrate chemotherapy, PTT, CDT, PDT, and other treatments is of great significance and offers great potential for the development of the next generation of anticancer nanomedicines. In view of the rapid development of Cu-based nanocomplexes in the field of cancer therapy, this review focuses on the current state of research on Cu-based nanomaterials, followed by a discussion of Cu-based nanocomplexes for combined cancer therapy. Moreover, the current challenges and future prospects of Cu-based nanocomplexes in clinical translation are proposed to provide some insights into the design of integrated Cu-based nanotherapeutic platforms.

Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA-H19 Driven Wnt/ß-Catenin Signaling Regulatory Axis.

Objectives: Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. Materials and Methods: The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/ß-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results: In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/ß-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/ß-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/ß-catenin signaling through promoting H19 expression. Conclusion: Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/ß-catenin regulatory axis.

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells.

Zhuo et al looked into the part of transmembrane 9 superfamily member 1 (TM9SF1) in bladder cancer (BC), and evaluated if it can be used as a therapeutic target. They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth, movement, invasion, and cell cycle advancement. Their results show that TM9SF1 can boost the growth, movement, and invasion of BC cells and their access into the G2/M stage of the cell cycle. This research gives a novel direction and concept for targeted therapy of BC.

The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study.

Background: While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods: Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn's disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value <5 × 10-8). Summary-level data for acute pancreatitis (AP), irritable bowel syndrome (IBS), gastroesophageal reflux disease, cholelithiasis, and CeD (celiac disease) were obtained from the GWAS meta-analysis and the FinnGen dataset. Summary-level data on relevant inflammatory factors were provided by the International Genetic Consortium. Univariate MR analysis was conducted using inverse variance weighting as the primary method for estimating causal effects. Multivariate MR analyses were also performed to detect possible mediators. Results: Genetic susceptibility to UC was associated with an increased risk of AP (OR = 1.08; 95% CI = 1.03-1.13; p=0.002) and IBS odds ratio (OR] = 1.07; 95% confidence interval (CI] = 1.03-1.11; (p < 0.001). In terms of potential mediators, interleukin 6 (IL-6) had a driving effect on the association between UC and AP. There was no apparent evidence of increased risk with CD. Meanwhile, genetic susceptibility to CD increases the risk of CeD (OR = 1.14; 95% CI = 1.03-1.25; p=0.01). Conclusions: The evidence suggests that UC is associated with an elevated risk of AP and IBS, and IL-6 may be responsible in AP. CD is associated with an increased risk of developing CeD. Implementing a proactive monitoring program for assessing the risk of gastrointestinal diseases in UC patients, particularly those with elevated IL-6 levels, may be of interest. In addition, the presence of AP and IBS may indicate the presence of UC. Preventing CeD is an essential consideration in the therapeutic management of patients with CD.

Investigation and analysis of magnetic resonance imaging experience and psychological status of patients.

OBJECTIVE: To analyze factors influencing the service experience of magnetic resonance imaging (MRI) examination and psychological status of patients admitted to a hospital and propose targeted solutions, and optimize the examination process and nursing by analyzing the MRI examination experience and psychological effect on patients. METHODS: The MRI examination rooms of two tertiary general hospitals in Haikou City were sampled at random, and 206 patients who met the study criteria were surveyed on site. RESULTS: (1) The item with the lowest mean score for patient examination services was whether earplugs were provided to the patient during the examination (B8 = 0.47). (2) Environmental logistics experience (16.83 ± 3.036) received the lowest score among the three service experience dimensions. (3) The average anxiety score of the patients was 5.38. (4) There was a positive correlation between the examination experience and the examination service experience of the patients. (5) Patients with higher monthly income had decreased anxiety (coefficient = -2.334), and MRI examination of the extremities relieved the anxiety (coefficient = -4.782). CONCLUSION: The environmental logistics factors, poor service attitude, examination site, and income were the most significant factors affecting the MRI examination experience and psychological status of patients, which can be improved by providing information, enhancing the waiting environment, providing targeted patient education, and evaluating the experience immediately.

EIF4A3-negatively driven circular RNA ß-catenin (circß-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.

Protective autophagy enhances antistress ability through AMPK/ULK1 signaling pathway in human immortalized keratinocytes.

Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low-dose ALA-PDT (0.5 mmol/L, 3 J/cm2). Through RNA-sequencing analysis, we identified that low-dose ALA-PDT modulated autophagy-related pathways in keratinocytes and pinpointed Unc-51-like kinase 1 (ULK1) as a key gene involved. Western blot results revealed that low-dose ALA-PDT treatment upregulated the expression of autophagy-related proteins Beclin-1 and LC3-II/LC3-I ratio. Notably, low-dose ALA-PDT regulated autophagy by inducing an appropriate level of reactive oxygen species (ROS), transiently reducing mitochondrial membrane potential, and decreasing adenosine triphosphate production; all these processes functioned on the AMP-activated protein kinase (AMPK)/ULK1 pathway to activate autophagy. Finally, we simulated external environmental damage using ultraviolet B (UVB) at a dose of 60 mJ/cm2 and observed that low-dose ALA-PDT mitigated UVB-induced cell apoptosis; however, this protective effect was reversed when using the autophagy inhibitor 3-methyladenine. Overall, these findings highlight how low-dose ALA-PDT enhances antistress ability in HaCaT cells through controlling ROS generation and activating the AMPK/ULK1 pathway to arouse cellular autophagy.

Effects of Aromatherapy on Physical and Mental Health of Cancer Patients Undergoing Radiotherapy and/or Chemotherapy: A Meta-Analysis.

BACKGROUP: Currently, aromatherapy is being increasingly utilized in clinical practice, particularly in managing the side effects associated with radiotherapy and chemoradiotherapy. However, it remains to be established whether aromatherapy can effectively alleviate these symptoms. OBJECTIVE: To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and chemotherapy. METHODS: Seven databases were researched from inception until September 29, 2023, including PubMed, Scopus, and Web of Science, Chinese National Knowledge Infrastructure, Wanfang database, China Biology Medicine disc and VIP Chinese Medical Journal Database. Review Manager version 5.3 was utilized for data analysis. The Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the study. Evidence quality rating was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach through the GRADEpro GDT online tool. RESULTS: Nineteen studies involving 1,541 patients were included. Aromatherapy can alleviate nausea [relative risk (RR)=0.64, 95% confidence interval (CI): 0.53 to 0.78, P<0.05, I2=46%; standardized mean difference (SMD)=-0.86, 95% CI: -1.21 to -0.51, P<0.05, I2=64%] and vomiting (RR=0.54, 95% CI: 0.42 to 0.69, P<0.05, I2=35%; SMD=-1.28, 95% CI: -1.52 to -1.03, P<0.05, I2=92%), improve sleep disorders [mean difference (MD)=-3.39, 95% CI: -3.95 to -2.84, P<0.05, I2=0%], relieve pain (SMD=-1.58, 95% CI: -1.96 to -1.21, P<0.05, I2=0%), mitigate fatigue (SMD=-1.28, 95% CI: -2.44 to -0.11, P<0.05, I2=93%) and enhance quality of life (SMD=0.50, 95% CI: 0.22 to 0.79, P<0.05, I2=0%) in cancer patients after radiotherapy and chemotherapy, but it may not have a significant effect on anxiety. The risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2, and no studies were considered to be of high grade according to the GRADE system. CONCLUSIONS: Aromatherapy is an efficacious, safe and economic adjunctive therapy for cancer patients, which can mend the physical symptoms and mental health of cancer patients. However, more high-quality studies are needed to verify it. (PROSPERO registration No. CRD42023390171).

Multi-strategy orthogonal enhancement and analysis of aldo-keto reductase thermal stability.

Given their outstanding efficiency and selectivity, enzymes are integral in various domains such as drug synthesis, the food industry, and environmental management. However, the inherent instability of natural enzymes limits their widespread industrial application. In this study, we underscore the efficacy of enhancing protein thermal stability through comprehensive protein design strategies, encompassing elements such as the free energy of protein folding, internal forces within proteins, and the overall structural design. We also demonstrate the efficiency and precision of combinatorial screening in the thermal stability design of aldo-keto reductase (AKR7-2-1). In our research, three single-point mutations and five combinatorial mutations were strategically introduced into AKR7-2-1, using multiple computational techniques. Notably, the E12I/S235I mutant showed a significant increase of 25.4 °C in its melting temperature (Tm). Furthermore, the optimal mutant, E12V/S235I, maintained 80 % of its activity while realizing a 16.8 °C elevation in Tm. Remarkably, its half-life at 50 °C was increased to twenty times that of the wild type. Structural analysis indicates that this enhanced thermal stability primarily arises from reduced oscillation in the loop region and increased internal hydrogen bonding. The promising results achieved with AKR7-2-1 demonstrate that our strategy could serve as a valuable reference for enhancing the thermal stability of other industrial enzymes.

Response to anti-HER2 neoadjuvant chemotherapy in HER2-positive invasive breast cancers with different HER2 FISH patterns.

AIMS: Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT. METHODS: 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers ≥6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0; group C: HER2/CEP17≥2.0 and HER2 copy numbers ≥6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups. RESULTS: According to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025). CONCLUSIONS: Patients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns.

Causal Relationship between Mitochondrial-Associated Proteins and Sepsis in ICU Patients: A Mendelian Randomization Study.

BACKGROUND: The alarming mortality rate of sepsis in ICUs has garnered significant attention. The precise etiology remains elusive. Mitochondria, often referred to as the cellular powerhouses, have been postulated to have a dysfunctional role, correlating with the onset and progression of sepsis. However, the exact causal relationship remains to be defined. METHOD: Employing the Mendelian randomization approach, this study systematically analyzed data from the IEUOpenGWAS and UKbiobank databases concerning mitochondrial function-related proteins and their association with sepsis, aiming to delineate the causal relationship between the two. RESULTS: The findings underscored a statistically significant association of GrpE1 with sepsis, registering a P value of 0.005 and an OR of 0.499 (95% CI: 0.307-0.810). Likewise, HTRA2, ISCU, and CUP3 each manifested significant associations with sepsis, yielding OR values of 0.585, 0.637, and 0.634, respectively. These results suggest potential implications of the aforementioned proteins in the pathogenesis of sepsis. CONCLUSION: The present study furnishes novel evidence elucidating the roles of GrpE1, HTRA2, ISCU, and CUP3 in the pathophysiology of sepsis. Such insights pave the way for a deeper understanding of the pathological mechanisms underpinning sepsis and hint at promising therapeutic strategies for the future.