A urethral leiomyoma presenting with dysuria: A rare case report.

RATIONALE: Leiomyoma is a benign smooth muscle tumor which is rarely found in urethra. We hereby report a case of a 44-year-old female who presented with complaints of dysuria. PATIENT CONCERNS: A 44-year-old female patient presented to the urology outpatient clinic with symptoms of dysuria. The patient described the presence of a protrusion from the urethra during urination. DIAGNOSIS: Urethral leiomyoma. INTERVENTIONS: Physical examination confirmed a solid urethral mass. CT scan and USG reports indicated that the mass originated from the mid-urethra with vascularity at the base. We performed a complete resection of the urethral mass. The patient was discharged after 3 days of observation. OUTCOME: During a follow-up after 1 month, the patient reported improved urinary flow and no occurrence of hematuria. The patient recovered well after discharge. LESSON: Urethral leiomyoma is a rare benign tumor that is often misdiagnosed in clinical practice. Diagnosis requires careful clinical examination. Surgical removal usually works well. It is important to remember that in some cases of acute urinary retention, it can be caused by a complete obstruction of a mass in the urethra. Urologists should be more cautious and experienced in handling such cases.

Innovative CF/PVC Foam Applicated for Automotive Synthetic Leather with High-Performance and Reduced VOC Emissions.

Polyvinyl chloride (PVC) foam, valued for its mechanical and thermal properties along with cost-effectiveness, is extensively utilized across diverse industries. However, its high volatile organic compound (VOC) emissions hinder its adoption in eco-friendly synthetic leather. This study proposes a solution by optimizing the formulation design and foaming processes and achieving mechanical property enhancement via carbon-fiber-reinforced PVC composite foam (CF/PVC). The aim is to reduce PVC usage via enhancing its intrinsic properties. Systematic investigations were carried out on the impact of foaming raw materials, foaming processes, fiber content, and fiber length on the foaming performance, mechanical properties, and VOC emissions. The material formulation and process parameters were successfully optimized. Further assessment of various indicators such as the density, mechanical properties, and tear resistance of synthetic leather samples confirmed that the innovative CF/PVC foam developed in this study meets the requirements for automotive interior applications. Notably, the tensile strength and tear resistance of CF/PVC composite synthetic leather increased by 50% and 29%, respectively, compared to pure PVC, while VOC emissions decreased by 28%. It is anticipated that a more pronounced reduction in VOC emissions will be achieved in practical automotive interior leather applications when further considering the reinforcing effect of fibers, which leads to a reduction in PVC usage. The findings present a technical reference for innovative applications, aiming to enhance PVC foam performance and minimize emissions.

Neurotoxic effects of heavy metal pollutants in the environment: Focusing on epigenetic mechanisms.

The pollution of heavy metals (HMs) in the environment is a significant global environmental issue, characterized by its extensive distribution, severe contamination, and profound ecological impacts. Excessive exposure to heavy metal pollutants can damage the nervous system. However, the mechanisms underlying the neurotoxicity of most heavy metals are not completely understood. Epigenetics is defined as a heritable change in gene function that can influence gene and subsequent protein expression levels without altering the DNA sequence. Growing evidence indicates that heavy metals can induce neurotoxic effects by triggering epigenetic changes and disrupting the epigenome. Compared with genetic changes, epigenetic alterations are more easily reversible. Epigenetic reprogramming techniques, drugs, and certain nutrients targeting specific epigenetic mechanisms involved in gene expression regulation are emerging as potential preventive or therapeutic tools for diseases. Therefore, this review provides a comprehensive overview of epigenetic modifications encompassing DNA/RNA methylation, histone modifications, and non-coding RNAs in the nervous system, elucidating their association with various heavy metal exposures. These primarily include manganese (Mn), mercury (Hg), lead (Pb), cobalt (Co), cadmium (Cd), nickel (Ni), sliver (Ag), toxic metalloids arsenic (As), and etc. The potential epigenetic mechanisms in the etiology, precision prevention, and target therapy of various neurodevelopmental disorders or different neurodegenerative diseases are emphasized. In addition, the current gaps in research and future areas of study are discussed. From a perspective on epigenetics, this review offers novel insights for prevention and treatment of neurotoxicity induced by heavy metal pollutants.

General practitioner residents' experiences and perceptions of outpatient training in primary care settings in China: a qualitative study.

OBJECTIVES: The implementation of outpatient training in primary care settings is an essential part of residency training for general practitioner (GP) residents. However, limited research exists on their experiences and perceptions of this training. This study aimed to explore the experiences and perceptions of GP residents regarding outpatient training in primary care settings in China and provide insights and recommendations to enhance training quality. DESIGN: A qualitative descriptive study employing in-depth interviews. SETTING: Two community healthcare centres (CHCs) that implement outpatient training programmes for GP residents in Zhejiang Province, China. PARTICIPANTS: In total, 20 GP residents affiliated with 14 CHCs and two hospitals across Zhejiang Province and Guizhou Province who had completed outpatient training in either CHC for over 1 month. RESULTS: Of the 20 participants in this study, 11 (55%) were women, and the mean age was 28 years. GP residents completed the process of consultation, physical examination and therapy independently; subsequently, the community preceptors provided feedback based on their clinical performance and modelled their clinical skills. The benefits perceived by GP residents included improved clinical skills and confidence in practice, and they learned approaches to maintaining good relationships with patients. They preferred dealing with complex cases, discussions with peers and the indirect supervision of community preceptors in the training session. Residents recommended that measures be taken to improve the training quality regarding patient selection and recruitment, clinical skills in the training session, and assessment of clinical performance. CONCLUSIONS: The outpatient training in primary care settings provides constructive opportunities for GP residents to improve their professional competencies. Although the current training sessions and the abilities of community preceptors largely satisfy the needs of GP residents, further research is needed to evaluate the effectiveness of training and explore approaches to improve its quality.

Effect of modified ShengYangYiwei decoction on painless gastroscopy and gastrointestinal and immune function in gastric cancer patients.

BACKGROUND: Painless gastroenteroscopy is a widely developed diagnostic and treatment technology in clinical practice. It is of great significance in the clinical diagnosis, treatment, follow-up review and other aspects of gastric cancer patients. The application of anesthesia techniques during manipulation can be effective in reducing patient fear and discomfort. In clinical work, the adverse drug reactions of anesthesia regimens and the risk of serious adverse drug reactions are increased with the increase in propofol application dose application dose; the application of opioid drugs often causes gastrointestinal reactions, such as nausea, vomiting and delayed gastrointestinal function recovery, after examination. These adverse effects can seriously affect the quality of life of patients. AIM: To observe the effect of modified ShengYangYiwei decoction on gastrointestinal function, related complications and immune function in patients with gastric cancer during and after painless gastroscopy. METHODS: A total of 106 patients with gastric cancer, who were selected from January 2022 to September 2022 in Xiamen Traditional Chinese Medicine Hospital for painless gastroscopy, were randomly divided into a treatment group (n = 56) and a control group (n = 50). Before the examination, all patients fasted for 8 h, provided their health education, and confirmed if there were contraindications to anesthesia and gastroscopy. During the examination, the patients were placed in the left decubitus position, the patients were given oxygen through a nasal catheter (6 L/min), the welling needle was opened for the venous channel, and a multifunction detector was connected for monitoring electrocardiogram, oxygen saturation, blood pressure, etc. Naporphl and propofol propofol protocols were used for routine anesthesia. Before anesthesia administration, the patients underwent several deep breathing exercises, received intravenous nalbuphine [0.nalbuphine (0.025 mg/kg)], followed by intravenous propofol [1.propofol (1.5 mg/kg)] until the palpebral reflex disappeared, and after no response, gastroscopy was performed. If palpebral reflex disappeared, and after no response, gastroscopy was performed. If any patient developed movement, frowning, or hemodynamic changes during the operation (heart rate changes during the operation (heart rate increased to > 20 beats/min, systolic blood pressure increased to > 20% of the base value), additional propofol [0.propofol (0.5 mg/kg)] was added until the patient was sedated again. The patients in the treatment group began to take the preventive intervention of Modified ShengYangYiwei decoction one week before the examination, while the patients in the control group received routine gastrointestinal endoscopy. The patients in the two groups were examined by conventional painless gastroscopy, and the characteristics of the painless gastroscopies of the patients in the two groups were recorded and compared. These characteristics included the total dosage of propofol during the examination, the incidence of complications during the operation, the time of patients' awakening, the time of independent activities, and the gastrointestinal function of the patients after examination, such as the incidence of reactions such as malignant vomiting, abdominal distension and abdominal pain, as well as the differences in the levels of various immunological indicators and inflammatory factors before anesthesia induction (T0), after conscious extubation (T1) and 24 h after surgery (T2). RESULTS: There was no difference in the patients' general information, American Society of Anesthesiologist classification or operation time between the two groups before treatment. In terms of painless gastroscopy, the total dosage of propofol in the treatment group was lower than that in the control group (P < 0.05), and the time of awakening and autonomous activity was significantly faster than that in the control group (P < 0.05). During the examination, the incidence of hypoxemia, hypotension and hiccups in the treatment group was significantly lower than that in the control group (P < 0.01). In terms of gastrointestinal function, the incidences of nausea, vomiting, abdominal distension and abdominal pain in the treatment group after examination were significantly lower than those in the control group (P < 0.01). In terms of immune function, in both groups, the number of CD4+ and CD8+ cells decreased significantly (P < 0.05), and the number of natural killer cells increased significantly (P < 0.05) at T1 and T2, compared with T0. The number of CD4+ and CD8+ cells in the treatment group at the T1 and T2 time points was higher than that in the control group (P < 0.05), while the number of natural killer cells was lower than that in the control group (P < 0.05). In terms of inflammatory factors, compared with T0, the levels of interleukin (IL) -6 and tumor necrosis factor-alpha in patients in the two groups at T1 and T2 increased significantly and then decreased (P < 0.05). The level of IL-6 at T1 and T2 in the treatment group was lower than that in the control group (P < 0.05). CONCLUSION: The preoperative use of modified ShengYangYiwei decoction can optimize the anesthesia program during painless gastroscopy, improve the gastrointestinal function of patients after the operation, reduce the occurrence of examination-related complications.

A genomic enhancer signature associates with hepatocellular carcinoma prognosis.

Background & Aims: Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC. Methods: We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis. Results: We observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients' tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis. Conclusions: We report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC. Impact and Implications: Lifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients' RNA-seq and clinical data, we found the signature genes - with epigenetic and transcriptomic dysregulation - associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.

Identifying the O3 chemical regime inferred from the weekly pattern of atmospheric O3, CO, NOx, and PM10: Five-year observations at a center urban site in Shanghai, China.

Ozone pollution is still considered a severe environmental problem in China despite the fact that great efforts have been devoted to monitoring and alleviating its impact by the Chinese government including the establishment of numerous observational networks. One of the issues most relevant to the design of emission reduction policies is to distinguish the O3 chemical regime. Here a method of quantifying the fraction of the radical loss versus NOx chemistry was applied to identify the O3 chemical regime inferred from the weekly pattern of atmospheric O3, CO, NOx, and PM10, which were monitored by Ministry of Ecology and Environment of China (MEEC). During spring and autumn, O3 and the total odd oxygen (Ox, Ox = O3 + NO2) weekend afternoon concentrations are both higher than the weekday values during 2015-2019 except in 2016, while CO and NOx weekend morning concentrations were generally both smaller than weekday values except 2017. Results from the calculated values of fraction of the radical loss by NOx chemistry relative to total radical loss (Ln/Q) suggested a volatile organic compound (VOC)-limited regime at this site in the spring of 2015-2019, as expected from the decreasing trend in NOx concentration and essentially constant CO after 2017. With respect to autumn, a shift from a transition regime during 2015-2017 to a VOC-limited regime in 2018 was found, which rapidly took place to a NOx-limited regime in 2019. No significant differences were detected in the Ln/Q values under different assumptions on photolysis frequencies both in spring and autumn mostly from 2015 to 2019, giving the same conclusion of determining the O3 sensitivity regime. This study develops a new method in determining the O3 sensitivity regime in the typical season in China and provides insight into efficient O3 control strategies in different seasons.

The deficiency of N6-methyladenosine demethylase ALKBH5 enhances the neurodegenerative damage induced by cobalt.

Cobalt exposure, even at low concentrations, induces neurodegenerative damage, such as Alzheimer's disease (AD). The specific underlying mechanisms remain unclear. Our previous study demonstrated that m6A methylation alteration is involved in cobalt-induced neurodegenerative damage, such as in AD. However, the role of m6A RNA methylation and its underlying mechanisms are poorly understood. In this study, both epidemiological and laboratory studies showed that cobalt exposure could downregulate the expression of the m6A demethylase ALKBH5, suggesting a key role for ALKBH5. Moreover, Methylated RNA immunoprecipitation and sequencing (MeRIP-seq) analysis revealed that ALKBH5 deficiency is associated with neurodegenerative diseases. KEGG pathway and Gene ontology analyses further revealed that the differentially m6A-modified genes resulting from ALKBH5 downregulation and cobalt exposure were aggregated in the pathways of proliferation, apoptosis, and autophagy. Subsequently, ALKBH5 deficiency was shown to exacerbate cell viability decline, motivate cell apoptosis and attenuate cell autophagy induced by cobalt with experimental techniques of gene overexpression/inhibition. In addition, morphological changes in neurons and the expression of AD-related proteins, such as APP, P-Tau, and Tau, in the cerebral hippocampus of wild-type and ALKBH5 knockout mice after chronic cobalt exposure were also investigated. Both in vitro and in vivo results showed that lower expression of ALKBH5 aggravated cobalt-induced neurodegenerative damage. These results suggest that ALKBH5, as an epigenetic regulator, could be a potential target for alleviating cobalt-induced neurodegenerative damage. In addition, we propose a novel strategy for the prevention and treatment of environmental toxicant-related neurodegeneration from an epigenetic perspective.

Study of wrist-ankle acupuncture therapy for optimizing anaesthesia scheme of painless gastroscopy and improving painless gastroscopy related complications.

BACKGROUND: Painless gastroscopy is a widely used diagnostic and therapeutic technology in clinical practice. Propofol combined with opioids is a common drug for painless endoscopic sedation and anaesthesia. In clinical work, adverse drug reactions of anaesthesia schemes are often one of the important areas of concern for doctors and patients. With the increase in propofol dosage, the risk of serious adverse drug reactions, such as respiratory depression and hypotension, increases significantly; the use of opioids often causes gastrointestinal reactions in patients after examination, such as nausea, vomiting, delayed recovery of gastrointestinal function and other complications, which seriously affect their quality of life. AIM: To observe the effect of wrist-ankle acupuncture therapy on the anaesthesia regimen and anaesthesia-related complications during and after painless gastroscopy examination. METHODS: Two hundred patients were selected and randomly divided into a treatment group (n = 100) and a control group (n = 100). Both groups were routinely anaesthetized with the nalbuphine and propofol regimen, gastroscopy began after the patient lost consciousness, and given supportive treatment and vital sign monitoring. If the patient interrupted the surgery due to intraoperative torsion, intravenous propofol was used to relieve his or her discomfort. The treatment group received wrist-ankle acupuncture on this basis. RESULTS: The general data before treatment, American Society of Anesthesiologist (ASA) grade and operation time between the two groups was no significant difference. The Wakeup time, and the Self-ambulation time in the treatment group was significantly faster than that in the control group (P < 0.05). The total dose of propofol in the treatment group was 109 ± 8.17 mg, significantly lower than that in the control group (P < 0.05). The incidence of respiratory depression and hypotension was not significantly different, but the incidence of hiccups was significantly lower than that in the control group (P < 0.05). After the examination, the incidence of nausea, vomiting, abdominal distension, and abdominal pain was 11%, 8%, 6%, and 5%, respectively, which was significantly lower than that in the control group (P < 0.05). In addition, both the operators and the patients were more satisfied with this examination, with no significant difference between the groups (P > 0.05). CONCLUSION: Wrist-ankle acupuncture treatment can optimize the painless gastroscopy and anaesthesia scheme, reduces propofol total dose; shortens patient Wakeup time and Self-ambulation time, improves patient compliance and tolerance, is beneficial to clinical application.

Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma.

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

Effect of Lactobacillus plantarum ZFM4 in Helicobacter pylori-infected C57BL/6 mice: prevention is better than cure.

Objectives: This study was performed to explore the preventive and therapeutic effects of Lactobacillus plantarum ZFM4 on H. pylori infections of the stomach tissue in C57BL/6 mice. Methods: In this study, 40 specific-pathogen-free female C57BL/6 mice were randomly divided into five groups, namely, the control, ZFM4 pretreatment) ZFM4 pretreatment before H. pylori infected), model (H. pylori infected), triple therapy (H. pylori infected and treated with triple therapy), and ZFM4 treatment groups (H. pylori infected and treated with ZFM4). The preventive and therapeutic effects of Lactobacillus plantarum ZFM4 were evaluated in H. pylori-infected C57BL/6 mice by assessing gastric tissue morphology, inflammatory cytokine levels, microbial composition, and microbial diversity. Results: Lactobacillus plantarum ZFM4 was able to survive in low gastric pH and play a role in preventing H. pylori infection. This was evident from a reduction in both, the gastric inflammatory response and expression of inflammatory factors caused by H. pylori infection. Lactobacillus plantarum ZFM4 could also inhibit the growth of H. pylori via its beneficial impact on the gastric microbiota. Conclusion: Our findings suggest that Lactobacillus plantarum ZFM4 offers superior preventive effects against H. pylori infections when used alone. However, the therapeutic effect on established infections is weaker. Further clinical trials are needed to confirm the specific dosage, duration, and other aspects of administration.

Helicobacter pylori infection eradication for nonalcoholic fatty liver disease: a randomized controlled trial.

Previous studies have suggested that Helicobacter pylori (H. pylori) infection is associated with nonalcoholic fatty liver disease (NAFLD). The purpose of the present study was to investigate the effect of H. pylori eradication treatment on NAFLD patients. Two hundred NAFLD patients who tested positive for H. pylori infection were randomized into the H. pylori eradication treatment group or the control group. Metabolic and inflammatory parameters and FibroScan were measured in all subjects at baseline and 1 year after treatment. At 1 year after treatment, the decrease in metabolic indicators, such as fasting blood glucose, glycosylated haemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, body mass index and controlled attenuation parameter values, were more obvious in the treatment group. Moreover, the inflammatory indicators white blood count and high-sensitivity C-reactive protein (hs-CRP) and the inflammatory factors interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) were also significantly decreased. H. pylori eradication can further reduce the metabolic indices of NAFLD and the degree of liver steatosis. H. pylori infection may participate in the occurrence and development of NAFLD through its influence on inflammatory factors. Thus, checking for the presence of H. pylori infection in patients at risk of NAFLD may be beneficial.

The immune escape signature predicts the prognosis and immunotherapy sensitivity for pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide. Immune escape is considered to be a reason for immunotherapy failure in PDAC. In this study, we explored the correlation between immune escape-related genes and the prognosis of PDAC patients. Methods: 1163 PDAC patients from four public databases, including The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Array-express, and Gene Expression Omnibus (GEO), were included in our study. Cox regression analysis was used to identify the 182 immune genes which were significantly associated with overall survival (OS). And then we established an immune escape-related gene prognosis index (IEGPI) score using several datasets as the training cohort and validated it using the validation cohort. Kaplan-Meier (KM) and Cox regression analysis were used to detect the relationship of IEGPI score with OS. We further explored the relationship between the IEGPI and immune indexes. And the prediction value of response for immunotherapy in Tumor Immune Dysfunction and Exclusion (TIDE) dataset. Results: We establish an IEGPI score based on 27 immune escape genes which were significantly related to the prognosis of OS in PDAC patients. Patients in the high-IEGPI group had a significantly worse overall survival rate compared with that in the low-IEGPI groups by KM curves and cox-regression. 5 of the 32 cancer types in TCGA could be significantly distinguished in survival rates through the low- and high-IEGPI groups. Moreover, the correlation between the IEGPI score was negatively correlated with an immune score in several datasets. And higher IEGPI better recurrence-free survival (RFS) and OS in the patients after patients were treated with both PD-1 and CTLA4 in the public datasets (P<0.05). Intriguingly, by using RT-PCR, we verified that the gene of PTPN2, CEP55, and JAK2 were all higher in the BxPC-3 and PANC-1 than HPDE5 cells. Lastly, we found that the IEGPI score was higher in K-rasLSL.G12D/+, p53LSL.R172H/+, Pdx1Cre (KPC) mice model with anti-PD-L1 than that without anti-PD-L1. Conclusion: Using the immune escape-related genes, our study established and validated an IEGPI score in PDAC patients from the public dataset. IEGPI score has the potential to serve as a prognostic marker and as a tool for selecting tumor patients suitable for immunotherapy in clinical practice.

3D Co-doped Ni-based conductive MOFs modified electrochemical sensor for highly sensitive detection of l-tryptophan.

L-tryptophan (Trp) is an essential amino acid for humans and plays crucial roles in many metabolic functions. Trp levels can be used for diagnosing different kinds of metabolic disorders and the symptoms associated with those diseases. Herein, a novel, simple and sensitive sensor based on 3D peony-like bimetallic conductive MOFs (Co-Ni-MOFs) was fabricated for the electrochemical determination of Trp. The bimetallic conductive MOFs were synthesized by a facile one-pot hydrothermal process. On account of the synergy between the Ni2+ and Co2+ ions, the bimetallic Co-Ni-MOFs showed excellent electrochemical performance, including good conductivity, large effective surface areas, and high electrocatalytic reactivity toward the oxidation of Trp. Consequently, the Co-Ni-MOFs-modified electrodes obtained a wide linear range from 10 nmol L-1 to 300 µmol L-1 and a low detection limit of 8.7 nmol L-1 (S/N = 3) for Trp. Additionally, the prepared sensor also displayed high selectivity, long-term stability and reproducibility. Moreover, the proposed sensor was successfully applied to determine the levels of Trp in the plasma of mice after cadmium intoxication.

Intensified wintertime secondary inorganic aerosol formation during heavy haze pollution episodes (HPEs) in Beijing, China.

Air pollution in China is complex, and the formation mechanism of chemical components in particulate matter is still unclear. This study selected three consecutive heavy haze pollution episodes (HPEs) during winter in Beijing for continuous field observation, including an episode with heavy air pollution under red alert. Clean days during the observation period were selected for comparison. The HPE characteristics of Beijing in winter were: under the influence of adverse meteorological conditions such as high relative humidity, temperature inversion and low wind speed; and strengthening of secondary transformation reactions, which further intensified the accumulation of secondary aerosols and other pollutants, promoting the explosive growth of PM2.5. PM2.5/CO values, as indicators of the contribution of secondary transformation in PM2.5, were approximately 2 times higher in the HPEs than the average PM2.5/CO during the clean period. The secondary inorganic aerosols (sulfate nitrate and ammonium salt) were significantly enhanced during the HPEs, and the conversion coefficients were remarkably improved. In addition, it is interesting to observe that the production of sulfate tended to exceed that of nitrate in the late stage of all three HPEs. The existence of aqueous phase reactions led to the explosive growth sulfur oxidation ratio (SOR) and rapid generation of sulfate under high relative humidity (RH>70%).

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma: the PLANET study.

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

Epigenetics in neurodegenerative disorders induced by pesticides.

Neurodegenerative diseases are becoming major socio-economic burdens. However, most of them still have no effective treatment. Growing evidence indicates excess exposure to pesticides are involved in the development of various forms of neurodegenerative and neurological diseases through trigger epigenetic changes and inducing disruption of the epigenome. This review summaries studies on epigenetics alterations in nervous systems in relation to different kinds of pesticides, highlighting potential mechanism in the etiology, precision prevention and target therapy of various neurodegenerative diseases. In addition, the current gaps in research and future areas for study were also discussed.

High NAFLD fibrosis score in non-alcoholic fatty liver disease as a predictor of carotid plaque development: a retrospective cohort study based on regular health check-up data in China.

PURPOSES: There is increasing concern regarding cardiovascular risk in non-alcoholic fatty liver disease (NAFLD) patients with liver fibrosis. This study aims: (1) to assess the association between NAFLD and liver fibrosis status and the development of carotid plaque (CP), and (2) to identify CP risk factors among general population with different baseline NAFLD and liver fibrosis status. METHODS: This retrospective cohort study included 14,288 adult participants who went for regular health check-ups between 2014 and 2019, in one hospital in Zhejiang, China. NAFLD was diagnosed by abdominal ultrasound and the NAFLD fibrosis score (NFS) was calculated to reflect the extent of liver fibrosis. Cox proportional hazards analyses were applied to assess the risk of CP development across groups with different baseline NAFLD and NFS status. RESULTS: NAFLD participants with high NFS had higher risk of CP compared to non-NAFLD participants (adjusted hazard ratio 1.68, 95% confidence interval [CI] 1.43-1.96, p < .001). Progression from NAFLD free and NAFLD with low NFS to NAFLD with high NFS are associated with 1.56-fold (95% CI 1.21-2.01, p = .001) and 1.43-fold (95% CI 1.11-1.84, p = .006) increased risk of CP, respectively. Risk factors associated with CP vary based on baseline NAFLD and NFS status. Among NAFLD participants with high NFS, hypertension is the only significant risk factor after adjustment for other potential influencing factors. CONCLUSIONS: NAFLD and liver fibrosis status can be an independent predictor for CP development regardless of metabolic abnormalities. Hypertension is a major risk factor for CP development among NAFLD patients with high NFS.KEY MESSAGESNon-alcoholic fatty liver disease (NAFLD) and liver fibrosis status can be an independent predictor for development of carotid plaque.Progression from NAFLD free and NAFLD with low NAFLD fibrosis score (NFS) to NAFLD with high NFS are associated with increased risk of carotid plaque.Risk factors associated with carotid plaque vary based on baseline NAFLD and NFS status, and hypertension plays the most important role among patients with NAFLD and high NFS.

Menopausal Women's Health Care Method Based on Computer Nursing Diagnosis Intelligent System.

Taking into account the current feature extraction speed and recognition effect of intelligent diagnosis of menopausal women's health care behavior, this paper proposes to use a cross-layer convolutional neural network to extract behavior features autonomously and use support vector machine multiclass behavior classifier to classify behavior. Compared with the feature images extracted by traditional methods, the behavioral features extracted in this paper are related to the individual menopausal women and have better semantic information, and the feature description ability in the time domain and the space domain has been enhanced. Through Matlab software, using the database established in this paper to compare its feature extraction time, test classification time, and final recognition accuracy with ordinary convolutional neural networks, it is concluded that the cross-layer CNN-SVM model can ensure the speed of feature extraction. It proves that the method in this paper can be applied to the behavioral intelligent diagnosis system for intelligently nursing menopausal women and has good practical value. This paper designs a home care bed intelligent monitoring system, which can automatically detect the posture of the care bed, and not only can change the posture of the bed under the control of personnel, but also can automatically complete the posture conversion according to the setting. At the same time, the system has the function of monitoring the physical condition of the person being cared for and can detect the heart rate, blood oxygen, and other physiological indicators of the bedridden person. In addition, the system can also provide a remote diagnosis function, allowing nursing staff to remotely view the current state of the nursing bed and the physical condition of the person. After testing, the system works stably, improves the automation and safety of the nursing bed control, and enriches the functions of the nursing bed.

Iron chelators reverse organ damage in type 4B hereditary hemochromatosis: Case reports.

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.