Physiologically based pharmacokinetic modeling in obesity: applications and challenges.

INTRODUCTION: Rising global obesity rates pose a threat to people's health. Obesity causes a series of pathophysiologic changes, making the response of patients with obesity to drugs different from that of nonobese, thus affecting the treatment efficacy and even leading to adverse events. Therefore, understanding obesity's effects on pharmacokinetics is essential for the rational use of drugs in patients with obesity. AREAS COVERED: Articles related to physiologically based pharmacokinetic (PBPK) modeling in patients with obesity from inception to October 2023 were searched in PubMed, Embase, Web of Science and the Cochrane Library. This review outlines PBPK modeling applications in exploring factors influencing obesity's effects on pharmacokinetics, guiding clinical drug development and evaluating and optimizing clinical use of drugs in patients with obesity. EXPERT OPINION: Obesity-induced pathophysiologic alterations impact drug pharmacokinetics and drug-drug interactions (DDIs), altering drug exposure. However, there is a lack of universal body size indices or quantitative pharmacology models to predict the optimal for the patients with obesity. Therefore, dosage regimens for patients with obesity must consider individual physiological and biochemical information, and clinically individualize therapeutic drug monitoring for highly variable drugs to ensure effective drug dosing and avoid adverse effects.

Extracellular vesicles-derived ferritin from lipid-induced hepatocytes regulates activation of hepatic stellate cells.

Introduction: and objectives: Extracellular vesicles (EVs) have emerged as key players in intercellular communication within the context of non-alcoholic fatty liver disease (NAFLD). This study aims to explore the intricate crosstalk between hepatocytes and hepatic stellate cells (HSCs) mediated by EVs in NAFLD. Materials and methods: EVs ferritin was detected in hepatocytes stimulated with free fatty acids (FFA) as well as in NAFLD mice. Deferoxamine (DFO) was employed to reduce ferritin levels, while GW4869 was utilized to inhibit EVs. The impact of EVs ferritin on the HSCs activation was evaluated both in vitro and in vivo. Additionally, serum EVs ferritin levels were compared between NAFLD patients and controls. Results: FFA treatment induces the formation and secretion of EVs and facilitates the release of ferritin from hepatocytes via EVs. Subsequently, EVs ferritin is hijacked by HSCs, prompting accelerated HSCs activation. Silencing ferritin with DFO and inhibiting EVs formation and secretion with GW4869 can reverse the effects of FFA treatment and disrupt the communication between hepatocytes and HSCs. Accumulation of ferritin leads to excessive reactive oxygen species (ROS) production, promoting HSCs fibrogenesis. Conversely, depleting EVs ferritin cargo restores liver function, concurrently mitigating NAFLD-associated fibrosis. Notably, NAFLD patients exhibit significantly elevated levels of serum EVs ferritin. Conclusions: This study unveils a previously underestimated role of ferritin in HSCs upon its release from hepatocytes, emphasizing DFO as a promising compound to impede NAFLD advancement.

Methyl jasmonate enhances the safe production ability of Cd-stressed wheat by regulating the antioxidant capacity, Cd absorption, and distribution in wheat.

Identifying green and effective measures for reducing wheat Cd toxicity and grain Cd accumulation is crucial. This study used seedling sand culture and full-grown pot experiments of wheat cultivars 'Luomai23' (LM) and 'Zhongyu10' (ZY). The purpose was to determine the effects of exogenous MeJA on the phenotype, photosynthesis, antioxidant system, Cd accumulation and distribution, transporter gene expression, and cell wall properties of Cd-stressed wheat. Compared with Cd treatment alone, the plant height and maximum root length treated with 0.001 µM MeJA increased by more than 6.3% and 16.6%, respectively. Under 5 mg⋅kg-1 Cd treatment, spraying 10 µM MeJA increased the photosynthetic rate of LM and ZY by 23.5% and 35.8% at the filling stage, respectively. Methyl jasmonate significantly reduced the H2O2 and MDA contents by increasing the activities of POD, DHAR, MDHAR, and GR and the contents of AsA and GSH. Applicating MeJA increased the content of chelate substances, cell wall polysaccharides, and cell wall functional groups. Besides, MeJA regulated the expression of Cd transporter genes, with shoot and root Cd content decreasing by 46.7% and 27.9% in LM, respectively. Spraying 10 µM MeJA reduced Cd absorption and translocation from vegetative organs to grains, thus reducing the grain Cd content of LM and ZY by 36.1 and 39.9% under 5 mg⋅kg-1 Cd treatment, respectively. Overexpressing TaJMT significantly increased the MeJA content and Cd tolerance of Arabidopsis. These results have improved the understanding of the mechanism through which MeJA alleviates Cd toxicity and reduces Cd accumulation in wheat.

A study of hemodynamic effects, postoperative recovery, and safety of esketamine (right handed) during flexible bronchoscopy under general anesthesia.

OBJECTIVE: Flexible bronchoscopy during general anesthesia has become an indispensable tool. Anesthetics are widely utilized in flexible bronchoscopy (FB). This study delved into the application value of a subanesthetic dose of esketamine (ES) (right handed) in flexible bronchoscopy during general anesthesia. METHODS: A sample of 160 patients who underwent flexible bronchoscopy during general anesthesia were selected as study subjects and were equally divided into the control and ES groups, with clinical baseline data (age, sex, body mass index, American Society of Anesthesiologists grading) collected. Hemodynamic parameters (mean artery pressure, heart rate, pulse blood oxygen saturation) at different time points, the onset time of anesthesia, surgery time, analgesia maintenance time, anesthesia awakening time, and perioperative adverse reactions were recorded. Visual analogue scale (VAS), Mini-Mental State Examination (MMSE), and quality of recovery-40 (QoR-40) scales were utilized for assessing post-surgery satisfaction, cognitive function, and post-surgery early recovery quality. RESULTS: The hemodynamics were stable at each time point, but patients in the ES group were more stable than those in the control group. Patients in the ES group exhibited faster onset and awakening time of anesthesia, longer duration of analgesia, and lower total incidence of adverse reactions versus the control group. The patients' QoR-40 total scores in the ES group were improved versus the control group at 1 day after surgery. CONCLUSION: Compared with fentanyl, the use of ES (right handed) in flexible bronchoscopy during general anesthesia produces more stable hemodynamics, faster onset and recovery time of anesthesia, longer duration of analgesia, lower incidence of adverse reactions, and improved early postoperative recovery quality in patients.

Clinical characteristics and prognosis of Klebsiella pneumoniae meningitis in adults.

Background: Klebsiella pneumoniae is a causative agent of bacterial meningitis in adults. However, there is little information regarding this infection. Therefore, this study comprehensively analyzed the clinical characteristics and prognosis of Klebsiella pneumoniae meningitis (KPM) patients. Methods: The clinical data of adult hospitalized patients with KPM were retrospectively collected from January 2015 to December 2022. The clinical characteristics and antibiotic resistance of KPM were evaluated. Meanwhile, a set of logistic regression models was constructed to identify prognostic factors for death. These prognostic factors were subsequently combined to develop a nomogram for predicting the risk of in-hospital mortality in individual patients. Finally, the receiver operating characteristic curve and calibrate plot were utilized to verify the performance of the nomogram. Results: This study included 80 adult patients with KPM, 58 (72.5%) of whom were males. The mortality rate was 45%. Among them, 74 (92.5%) were diagnosed with healthcare-associated meningitis. Thirty-seven carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were susceptible to tigecycline, polymyxin, and ceftazidime/avibactam. CRKP (OR = 9.825, 95%CI = 2.757-35.011, P < 0.001), length of stay (OR = 0.953, 95%CI = 0.921-0.986, P = 0.005), and C-reactive protein-to-prealbumin ratio (CRP/PA, OR = 3.053, 95%CI = 1.329-7.016, P = 0.009) were identified as predictive factors for mortality using multivariate logistic regression. Finally, a nomogram for death prediction was established. The area under the curve of this nomogram was 0.900 (95% CI = 0.828-0.971). Conclusions: KPM is a fatal disease associated with high incidence of healthcare-associated infections and carbapenem resistance. Moreover, CRKP, length of stay, and CRP/PA were found to be independent predictors of mortality.

[A survey of parents of preschool children on their perception of bad oral habits].

PURPOSE: Through questionnaire survey, parents' cognition of children's bad oral habits and their related influencing factors were explored, in order to provide a reference for science popularization and education in future work. METHODS: With a self-designed questionnaire, 247 parents of children at first visit were surveyed on basic information and problems related to bad oral habits. Descriptive statistics were used for the counting data. Logistic regression analysis was used for the relevant factors affecting the parents' cognition of children's bad oral habits with SPSS 26.0 software package. RESULTS: Among 247 parents of preschool children, 17.4% of the parents took their children to the hospital for treatment because of bad oral habits. The prevalence of oral unhealthy habits was 44%. Parents' knowledge of bad oral habits was not high, less than half of the parents (46.6%) knew about bad oral habits, of which 82.6% of the parents thought that bad oral habits would affect the development of children's teeth, jaws, face and mental health, including facial contour (62.1%), dentition (34.7%), masticatory function (48.4%), and mental health (21.1%). 78.3% of the parents thought that bad oral habits needed to be corrected; 69.6% of the parents thought that they needed to go to the hospital for treatment, and 30.4% of the parents thought that it was ok as long as their children giving up bad oral habits. 61.7% of the parents would seek medical treatment in time when their children had bad oral habits. The ways for parents to obtain knowledge about bad oral habits were hospital education (61.5%). Parents with different characteristics had different cognition of bad oral habits. Logistic regression analysis showed that parents' education background was a risk factor affecting parents' cognition of bad oral habits(P=0.009). CONCLUSIONS: Parents' awareness of bad oral habits is not high, and parents' educational background is a risk factor for parents' awareness of bad oral habits. It is necessary to improve parents' awareness of oral habits, strengthen health education of bad oral habits, especially for parents with special signs, and improve the attention to oral health care, to achieve early detection, early prevention, early treatment and timely treatment, so as to prevent the occurrence and development of malocclusion.

The causal impact of complement C3d receptor 2 on head and neck cancer microenvironment and its implications for immunotherapy response prediction.

This research dives into the intricate immune landscape of head and neck cancer (HNC), with a keen focus on the roles of specific immune cell subpopulations and their linked genes. We used tumour RNA-seq (in-house cohort: n = 192, TCGA-HNSC: n = 546) and Mendelian randomization to pinpoint key SNPs in immune cells that have a causal connection to HNC. Our discoveries unveil a spectrum of tumour immune phenotypes that either offer protection against or increase the risk of HNC. We underscore the therapeutic promise of Complement C3d Receptor 2 (CR2), a gene closely tied to immune cells, with its increased expression in tumour tissues linked to a more favourable prognosis. This is correlated with heightened immune pathway activity, stronger resistance to radiochemotherapy, and improved immunotherapy responses. Our research emphasises the pivotal role of CR2 in immune regulation and the significance of immune cells in tumour progression, highlighting the potential of CR2-targeted therapeutic interventions.

A progress update on the biological effects of biodegradable microplastics on soil and ocean environment: A perfect substitute or new threat?

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plants, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

Non-coding RNA-related FCGBP downregulation in head and neck squamous cell carcinoma: a novel biomarker for predicting paclitaxel resistance and immunosuppressive microenvironment.

In head and neck squamous cell carcinoma (HNSC), chemoresistance is a major reason for poor prognosis. Nevertheless, there is a lack of validated biomarkers to screen for patients for categorical chemotherapy. Fc gamma binding protein (FCGBP) is a mucus protein associated with mucosal epithelial cells and has immunological functions that protect against tumors and metastasis. However, the effect of FCGBP on HNSC is unclear. In pan-cancer tissues, the expression of FCGBP and the survival status of patients were analyzed using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Correlation analysis and Cox regression analysis were conducted to confirm the relationship and survival outcome. Bioinformatics analysis was utilized to predict the probable upstream non-coding RNA. FCGBP functioned as a potential tumor suppressor gene in HNSC. Notably, FCGBP expression was negatively correlated with enriched tumor-infiltrating macrophages and paclitaxel resistance. Cox regression with gene, clinical, and immune factors showed that FCGBP was a risk factor acting in an independent manner. In HNSC, the utmost possibly upstream non-coding RNA-related pathway of FCGBP was also discovered to be the PART1/AC007728.2/LINC00885/hsa-miR-877-5p/FCGBP axis. According to the present study, non-coding RNA-related low levels of FCGBP are a prognostic indicator and are linked to an HNSC-related immunosuppressive state.

Identification of novel molecular subtypes to improve the classification framework of nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) treatment is largely based on a 'one-drug-fits-all' strategy in patients with similar pathological characteristics. However, given its biological heterogeneity, patients at the same clinical stage or similar therapies exhibit significant clinical differences. Thus, novel molecular subgroups based on these characteristics may better therapeutic outcomes. METHODS: Herein, 192 treatment-naïve NPC samples with corresponding clinicopathological information were obtained from Fujian Cancer Hospital between January 2015 and January 2018. The gene expression profiles of the samples were obtained by RNA sequencing. Molecular subtypes were identified by consensus clustering. External NPC cohorts were used as the validation sets. RESULTS: Patients with NPC were classified into immune, metabolic, and proliferative molecular subtypes with distinct clinical features. Additionally, this classification was repeatable and predictable as validated by the external NPC cohorts. Metabolomics has shown that arachidonic acid metabolites were associated with NPC malignancy. We also identified several key genes in each subtype using a weighted correlation network analysis. Furthermore, a prognostic risk model based on these key genes was developed and was significantly associated with disease-free survival (hazard ratio, 1.11; 95% CI, 1.07-1.16; P < 0.0001), which was further validated by an external NPC cohort (hazard ratio, 7.71; 95% CI, 1.39-42.73; P < 0.0001). Moreover, the 1-, 3-, and 5-year areas under the curve were 0.84 (95% CI, 0.74-0.94), 0.81 (95% CI, 0.73-0.89), and 0.82 (95% CI, 0.73-0.90), respectively, demonstrating a high predictive value. CONCLUSIONS: Overall, we defined a novel classification of nasopharyngeal carcinoma (immune, metabolism, and proliferation subtypes). Among these subtypes, metabolism and proliferation subtypes were associated with advanced stage and poor prognosis of NPC patients, whereas the immune subtype was linked to early stage and favorable prognosis.

Effects of nutritional indices and inflammatory parameters on patients received immunotherapy for non-small cell lung cancer.

OBJECTIVE: This research explored the relationship between a patient's nutritional state and inflammatory markers and the prognosis of their non-small cell lung cancer (NSCLC) treatment while receiving a combination of chemotherapy and immunotherapy. METHOD: This retrospective and single-center analysis included NSCLC patients who received a combination of chemotherapy and immunotherapy at the Department of Oncology at Shanghai Lung Hospital. Patients were categorized based on malnutrition, sarcopenia, sarcopenic obesity, and advanced-lung-cancer-inflammation-index (ALI) scores after collecting nutritional and inflammatory indices. Kaplan-Meier and the Cox models were utilized to analyze survival. RESULTS: There was a significant correlation between malnutrition, sarcopenia, sarcopenic obesity, and low ALI scores with lower overall survival (OS) and progression-free survival (PFS) (p < 0.05). Low ALI score and malnutrition were independent factors influencing patient survival in terms of both OS and PFS (p < 0.01). CONCLUSION: The nutritional and inflammatory indices of immunotherapy-treated NSCLC patients substantially affect their prognosis. Assessing these variables could aid in optimizing treatment strategies and improving patient outcomes. Additional research is required to comprehend the intricate relationship between nutrition, inflammation, and cancer progression and to develop individualized therapies.

Use of the Hall Technique by dentists in East China: A questionnaire-based cross-sectional survey.

BACKGROUND: The Hall Technique (HT) is now regarded as one of the biological management options for carious primary molars and has shown significant clinical success. AIM: To investigate the perception and the use of the HT among dentists engaging in paediatric dentistry in East China. DESIGN: This was an electronic questionnaire-based cross-sectional study. A quick response code of the questionnaire via WeChat, a common communication tool in China, was sent to dentists in East China. RESULTS: A total of 313 dentists participated in this study. Most surveyed clinicians had heard about the HT (n = 286, 91.4%). Of them, 40.2% (n = 115) reported having used the HT. Of 67 dentists working in private clinics, 34 (50.7%) had used the HT, whereas only 37% of dentists from public hospitals had used the HT. Of 115 dentists having used the HT, 91.3% (n = 105) would consider using the HT for Class II cavitated molars; 23.5% (n = 27) would consider using the HT for Class I cavitated molars. Most dentists who had not used the HT were concerned about complications such as pulp inflammation or necrosis after applying the HT. CONCLUSION: The HT is well known in East China; the lack of systematic training or courses, however, may decrease its utilization.

Anti-Ulcerative Colitis Effects and Active Ingredients in Ethyl Acetate Extract from Decoction of Sargentodoxa cuneata.

Ulcerative colitis (UC) is an intractable disease prevalent worldwide. While ethyl acetate extract from decoction of Sargentodoxa cuneata (EAdSc) has potential anti-inflammatory activity, its effects on UC remain unknown. In this study, the constituent compounds discussed in the literature and identified by gas chromatography and mass spectrometry (GC-MS) were collected, and the blood-soluble components of EAdSc were identified by liquid chromatography-mass spectrometry. The network pharmacology analysis and molecular docking analysis were performed to explore the potential underlying mechanism and active ingredients of EAdSc against UC. Furthermore, mice with dextran sulfate sodium (DSS)-induced UC were used to study the therapeutic effects and validate the mechanism of EAdSc against UC. A total of 53 compounds from EAdSc were identified in the literature and by GC-MS, and 22 blood-soluble EAdSc components were recognized. Network pharmacology analysis revealed that multiple inflammatory signaling pathways are involved in EAdSc's anti-UC activity. Furthermore, molecular docking analysis showed that the eleutheroside A, liriodendrin, epicatechin, 2-methoxy-4-vinylphenol, catechin, androsin, coumaroyltyramine, and catechol may be active against UC through the TLR4/NF-κB/NLRP3 pathway. EAdSc reduced the disease activity, macroscopic colon damage, and histological damage indices, as well as inhibiting DSS-induced spleen enlargement and colon shortening. In addition, EAdSc decreased the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-17, as well as the expression of TLR4, NF-κB p65, NLRP3, and Caspase-1 mRNA in colon tissues. These results provide insights into the anti-UC effects and underlying mechanisms of EAdSc and help elucidate the active ingredients of EAdSc in the treatment of UC.

Effect of neoadjuvant chemotherapy on the immune microenvironment of gynaecological tumours.

Purpose: To assess the impact of neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment (TIME) in gynaecological tumors, with a focus on understanding the potential for enhanced combination therapies.Methods: We systematically queried the PubMed, Embase, and Cochrane databases, encompassing reviews, clinical trials, and case studies, to undertake a thorough analysis of the impact of NACT on the TIME of gynaecological tumors.Results: NACT induces diverse immune microenvironment changes in gynaecological tumors. In cervical cancer, NACT boosts immune-promoting cells, enhancing tumor clearance. Ovarian cancer studies yield variable outcomes, influenced by patient-specific factors and treatment regimens. Limited research exists on NACT's impact on endometrial cancer's immune microenvironment, warranting further exploration. In summary, NACT-induced immune microenvironment changes display variability. Clinical trials highlight personalized immunotherapy's positive impact on gynaecological tumor prognosis, suggesting potential avenues for future cancer treatments. However, rigorous investigation is needed to determine the exact efficacy and safety of combining NACT with immunotherapy.Conclusion: This review provides a solid foundation for the development of late-stage immunotherapy and highlights the importance of therapeutic strategies targeting immune cells in TIME in anti-tumor therapy.

The abnormal tumour microenvironment in gynaecological tumours can impede the penetration and accumulation of chemotherapeutic drugs, leading to poorer drug therapy efficacy.Neoadjuvant chemotherapy can improve the surgical resection rate of patients while regulating the ratio of each immune cell subpopulation to achieve the regulation of the tumour microenvironment, thus achieving anti-tumour effects.Based on the immune variability of patients after neoadjuvant chemotherapy, selecting the most suitable individualized immunotherapy will become a promising new therapy.

Pharmacokinetics, safety, and efficacy of GM1 ganglioside in healthy subjects and patients with multiple myeloma: Two dose-escalation studies.

PURPOSE: This study aimed to assess the pharmacokinetics, safety, and efficacy of GM1 in healthy Chinese subjects and patients with multiple myeloma. METHODS: The data used in this study was derived from two dose-escalation trials: GM1-101, involving 70 healthy subjects, and GM1-201, which included 160 multiple myeloma patients. Population pharmacokinetics (PopPK) analysis was conducted on a subset of 90 participants using a nonlinear mixed-effects approach, and potential covariates were explored quantitatively. Observations of any abnormalities in vital signs, physical examinations, laboratory tests, and electrocardiograms during the study period, along with any spontaneously reported and directly observed adverse events, were documented for safety evaluation. Furthermore, neurotoxicity scales were used to assess the efficacy of GM1 as a prophylaxis for chemotherapy-induced peripheral neuropathy and to perform exposure-response analyses in conjunction with pharmacokinetic parameters. RESULTS: A one-compartment model with first-order elimination best characterized the pharmacokinetics of GM1. The clearance and volume of distribution, as estimated by the final model, were 0.0942 L/h and 3.27 L for GM1-A, and 0.0714 L/h and 2.82 L for GM1-B, respectively. Covariates such as sex, body weight, and albumin significantly influenced pharmacokinetic parameters, yet the variation in steady-state exposure between subjects and reference subjects was less than 45% within their 90% confidence interval. Adverse reactions related to GM1 occurred in 20 (28.6%) and 57 (35.6%) subjects in the GM1-101 and GM1-201 cohorts, respectively. The changes in TNSc and FACT-Ntx scores from baseline at the end of periods 4 and 6 were lower in each GM1 dose group compared to the blank control group. The 400 mg dose group of GM1 displayed greater effectiveness than other dose groups. However, exposure-response analysis revealed no significant modification in efficacy with increasing GM1 exposure. CONCLUSIONS: This study provides the first population pharmacokinetic analysis of GM1. GM1 exhibits a favorable safety profile among healthy subjects and patients with multiple myeloma. GM1 proved effective in mitigating chemotherapy-induced peripheral neuropathy, but this study observed no significant correlation between its efficacy and exposure. TRIAL REGISTRATION NUMBERS: ChiCTR2000041283 and ChiCTR2000041283.

Nutritional status in patients with active pulmonary tuberculosis and new nutritional risk screening model for active tuberculosis: a national, multicenter, cross-sectional study in China.

Background: Tuberculosis (TB) remains a significant challenge for public health and is closely associated with malnutrition; however, few studies have attempted to screen malnutrition among TB patients. The study aimed to evaluate the nutrition status and build a new nutritional screening model for active TB. Methods: A retrospective, multicenter, large cross-sectional study was conducted in China from 1 January 2020 to 31 December 2021. All included patients diagnosed with active pulmonary TB (PTB) were evaluated both by Nutrition Risk Screening 2002 (NRS 2002) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Univariate and multivariate analyses were conducted to screen the risk factors associated with malnutrition, and a new screening risk model, mainly for TB patients, was constructed. Results: A total of 14,941 cases meeting the inclusion criteria were entered into the final analysis. The malnutrition risk rate among PTB patients in China was 55.86% and 42.70%, according to the NRS 2002 and GLIM, respectively. The inconsistency rate between the two methods was 24.77%. A total of 11 clinical factors, including elderly, low body mass index (BMI), decreased lymphocyte cells, taking immunosuppressive agents, co-pleural TB, diabetes mellitus (DM), human immunodeficiency virus (HIV), severe pneumonia, decreased food intake within a week, weight loss and dialysis were identified as independent risk factors of malnutrition based on multivariate analyses. A new nutritional risk screening model was constructed for TB patients with a diagnostic sensitivity of 97.6% and specificity of 93.1%. Conclusions: Active TB patients have severe malnutrition status according to screening by the NRS 2002 and GLIM criteria. The new screening model is recommended for PTB patients as it is more closely tailored to the characteristics of TB.

Prognostic model on overall survival in elderly nasopharyngeal carcinoma patients: a recursive partitioning analysis identifying pre-treatment risk stratification.

BACKGROUND: We aimed to evaluate the optimal management for elderly patients with nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT). METHODS: A total of 283 elderly patients with NPC diagnosed from 2015 to 2019 were enrolled in the study. Overall survival (OS) was the primary endpoint. Univariate and multivariate Cox regression analyses were preformed to identify potential prognostic factors. The recursive partitioning analysis (RPA) was used for risk stratification. Kaplan-Meier survival curves were applied to evaluate the survival endpoints, and log-rank test was utilized to assess differences between groups. The prognostic index (PI) was constructed to further predict patients' prognosis displayed by nomogram model. The area under the receiver operating characteristic (ROC) curves (AUC) and the calibration curves were applied to assess the effectiveness of the model. RESULTS: Based on RPA-based risk stratification, we demonstrated that elderly NPC patients who were treated with IC followed by RT had similar OS as those with induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) in the middle- (stage I-III and pre-treatment EBV > 1840 copies/ml) and high-risk groups (stage IVA). IMRT alone may be the optimal treatment option for the low-risk group (stage I-III with pre-treatment EBV ≤ 1840 copies/ml). We established an integrated PI which was indicted with stronger prognostic power than each of the factors alone for elderly NPC patients (The AUC of PI was 0.75, 0.80, and 0.82 for 1-, 3-, 5-year prediction of OS, respectively). CONCLUSION: We present a robust model for clinical stratification which could guide individual therapy for elderly NPC patients.

Circulating DNA methylation level of CXCR5 correlates with inflammation in patients with rheumatoid arthritis.

OBJECTIVES: To assess the differences in circulating DNA methylation levels of CXCR5 between rheumatoid arthritis (RA) and osteoarthritis (OA) and healthy controls (HC), and the correlation of methylation changes with clinical characteristics of RA patients. METHODS: Peripheral blood samples were collected from 239 RA patients, 30 patients with OA, and 29 HC. Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis. RESULTS: The methylation level of cg04537602 was significantly higher in the peripheral blood of RA patients compared with OA patients (p = 1.3 × 10-3 ) and in the HC group (p = 5.5 × 10- 4 ). The sensitivity was enhanced when CXCR5 methylation level combined with rheumatoid factor and anti-cyclic citrullinated peptide with area under curve (AUC) of 0.982 (95% confidence interval 0.970-0.995). The methylation level of cg04537602 in RA was positively correlated with C-reactive protein (CRP) (r = .16, p = .01), and in RA patients aged 60 years and above, cg04537602 methylation levels were positively correlated with CRP (r = .31, p = 4.7 × 10- 4 ), tender joint count (r = .21, p = .02), visual analog scales score (r = .21, p = .02), Disease Activity Score in 28 joints (DAS28) using the CRP level DAS28-CRP (r = .27, p = 2.1 × 10- 3 ), and DAS28-ESR (r = .22, p = .01). We also observed significant differences of DNA methylation haplotypes in RA patients compared with OA patients and HC, which was consistent with single-loci-based CpG methylation measurement. CONCLUSION: The methylation level of CXCR5 was significantly higher in RA patients than in OA and HC, and correlated with the level of inflammation in RA patients, our study establishes a link between CXCR5 DNA methylation and clinical features that may help in the diagnosis and disease management of RA patients.

Peptide-Functionalized Prussian Blue Nanomaterial for Antioxidant Stress and NIR Photothermal Therapy against Alzheimer's Disease.

Excessive accumulations of reactive oxygen species (ROS) and amyloid-ß (Aß) protein are closely associated with the complex pathogenesis of Alzheimer's disease (AD). Therefore, approaches that synergistically exert elimination of ROS and dissociation of Aß fibrils are effective therapeutic strategies for correcting the AD microenvironment. Herein, a novel near infrared (NIR) responsive Prussian blue-based nanomaterial (PBK NPs) is established with excellent antioxidant activity and photothermal effect. PBK NPs possess similar activities to multiple antioxidant enzymes, including superoxide dismutase, peroxidase, and catalase, which can eliminate massive ROS and relieve oxidative stress. Under the NIR irradiation, PBK NPs can generate local heat to disaggregate Aß fibrils efficiently. By modifying CKLVFFAED peptide, PBK NPs display obvious targeting ability for blood-brain barrier penetration and Aß binding. Furthermore, in vivo studies demonstrate that PBK NPs have outstanding ability to decompose Aß plaques and alleviate neuroinflammation in AD mouse model. Overall, PBK NPs provide evident neuroprotection by reducing ROS levels and regulating Aß deposition, and may accelerate the development of multifunctional nanomaterials for delaying the progression of AD.

An immune-related prognostic model predicts neoplasm-immunity interactions for metastatic nasopharyngeal carcinoma.

Background: The prognosis of nasopharyngeal carcinoma (NPC) has been recognized to improve immensely owing to radiotherapy combined with chemotherapy. However, patients with metastatic NPC have a poor prognosis. Immunotherapy has dramatically prolonged the survival of patients with NPC. Hence, further research on immune-related biomarkers is imperative to establish the prognosis of metastatic NPC. Methods: 10 NPC RNA expression profiles were generated from patients with or without distant metastasis after chemoradiotherapy from the Fujian Cancer Hospital. The differential immune-related genes were identified and validated by immunohistochemistry analysis. The method of least absolute shrinkage and selection operator (LASSO)was used to further establish the immune-related prognostic model in an external GEO database (GSE102349, n=88). The immune microenvironment and signal pathways were evaluated in multiple dimensions at the transcriptome and single-cell levels. Results: 1328 differential genes were identified, out of which 520 were upregulated and 808 were downregulated. Notably, most of the immune genes and pathways were down-regulated in the metastasis group. A prognostic immune model involving nine hub genes. Patients in low-risk group were characterized by survival advantage, hot immune phenotype and benefit from immunotherapy. Compared with immune cells, malignant cell exhibited the most active levels of risk score by ssGSEA. Accordingly, intercellular communications including LT, CD70, CD40 and SPP1, and the like, between high-risk and low-risk were explored by the R package "Cellchat". Conclusion: We have constructed a model based on immunity of metastatic NPC and determined its prognostic value. The model identified the level of immune cell infiltration, cell-cell communication, along with potential immunotherapy for metastatic NPC.