Non-negligible N2O emission hotspots: Rivers impacted by ion-adsorption rare earth mining.

Rare earth mining causes severe riverine nitrogen pollution, but its effect on nitrous oxide (N2O) emissions and the associated nitrogen transformation processes remain unclear. Here, we characterized N2O fluxes from China's largest ion-adsorption rare earth mining watershed and elucidated the mechanisms that drove N2O production and consumption using advanced isotope mapping and molecular biology techniques. Compared to the undisturbed river, the mining-affected river exhibited higher N2O fluxes (7.96 ± 10.18 mmol m-2d-1 vs. 2.88 ± 8.27 mmol m-2d-1, P = 0.002), confirming that mining-affected rivers are N2O emission hotspots. Flux variations scaled with high nitrogen supply (resulting from mining activities), and were mainly attributed to changes in water chemistry (i.e., pH, and metal concentrations), sediment property (i.e., particle size), and hydrogeomorphic factors (e.g., river order and slope). Coupled nitrification-denitrification and N2O reduction were the dominant processes controlling the N2O dynamics. Of these, the contribution of incomplete denitrification to N2O production was greater than that of nitrification, especially in the heavily mining-affected reaches. Co-occurrence network analysis identified Thiomonas and Rhodanobacter as the key genus closely associated with N2O production, suggesting their potential roles for denitrification. This is the first study to elucidate N2O emission and influential mechanisms in mining-affected rivers using combined isotopic and molecular techniques. The discovery of this study enhances our understanding of the distinctive processes driving N2O production and consumption in highly anthropogenically disturbed aquatic systems, and also provides the foundation for accurate assessment of N2O emissions from mining-affected rivers on regional and global scales.

Development of a new prognostic index PNPI for prognosis prediction of CKD patients with pneumonia at hospital admission.

Background: The aim of this study was to investigate the relationship between pneumonia and chronic kidney disease (CKD), to elucidate potential risk factors, and to develop a new predictive model for the poor prognosis of pneumonia in CKD patients. Method: We conducted a retrospective observational study of CKD patients admitted to Tongji Hospital between June 2012 and June 2022. Demographic information, comorbidities or laboratory tests were collected. Applying univariate and multivariate logistic regression analyses, independent risk factors associated with a poor prognosis (i.e., respiratory failure, shock, combined other organ failure, and/or death during hospitalization) for pneumonia in CKD patients were discovered, with nomogram model subsequently developed. Predictive model was compared with other commonly used pneumonia severity scores. Result: Of 3,193 CKD patients with pneumonia, 1,013 (31.7%) met the primary endpoint during hospitalization. Risk factors predicting poor prognosis of pneumonia in CKD patients were selected on the result of multivariate logistic regression models, including chronic cardiac disease; CKD stage; elevated neutrophil to lymphocyte ratio (NLR) and D-dimer; decreased platelets, PTA, and chloride iron; and significant symptom presence and GGO presentation on CT. The nomogram model outperformed other pneumonia severity indices with AUC of 0.82 (95% CI: 0.80, 0.84) in training set and 0.83 (95% CI: 0.80, 0.86) in testing set. In addition, calibration curve and decision curve analysis (DCA) proved its efficiency and adaptability. Conclusion: We designed a clinical prediction model PNPI (pneumonia in nephropathy patients prognostic index) to assess the risk of poor prognosis in CKD patients with pneumonia, which may be generalized after more external validation.

Pollution caused by mining reshaped the structure and function of bacterial communities in China's largest ion-adsorption rare earth mine watershed.

Ion-adsorption rare earth mining results in the production of high levels of nitrogen, multiple metals, and strong acidic mine drainage (AMD), the impacts of which on microbial assembly and ecological functions remain unclear. To address this knowledge gap, we collected river sediments from the watershed of China's largest ion-adsorption rare earth mine and analyzed the bacterial community's structure, function, and assembly mechanisms. Results showed that bacterial community assembly was weakly affected by spatial dispersion, and dispersal limitation and homogeneous selection were the dominant ecological processes, with the latter increasing with pollution gradients. Bacterial alpha diversity decreased with pollution, which was mainly influenced by lead (Pb), pH, rare earth elements (REEs), and electrical conductivity (EC). However, bacteria developed survival strategies (i.e., enhanced acid tolerance and interspecific competition) to adapt to extreme environments, sustaining species diversity and community stability. Community structure and function showed a consistent response to the polluted environment (r = 0.662, P = 0.001). Enhanced environmental selection reshaped key microbial-mediated biogeochemical processes in the mining area, in particular weakening the potential for microbial denitrification. These findings provide new insights into the ecological response of microbes to compound pollution and offer theoretical support for proposing effective remediation and management strategies for polluted areas.

Clinical characteristics and risk factor analysis of Pneumocystis jirovecii pneumonia in patients with CKD: a machine learning-based approach.

Patients with chronic kidney disease (CKD) who are being treated with immunosuppressive medications are at risk for developing Pneumocystis jirovecii pneumonia (PCP). We attempted to characterize the clinical aspects of PCP in CKD patients in order to alert high-risk patients with bad prognosis. A retrospective study of CKD patients was conducted from June 2018 to June 2022. Based on PCP diagnostic criteria, these patients were divided into PCP and non-PCP groups. Using univariate and multivariate logistic regression analysis, risk indicators were evaluated, and nomogram and decision tree were developed. Of the CKD patients screened for Pneumocystis carinii nucleic acid, 1512 were included. Two-hundred forty four (16.14%) were diagnosed with PCP. Of the PCP, 88.5% was receiving glucocorticoid (GC) therapy, of which 66.3% received more than 0.5 mg/kg GC. Multivariate analysis showed that membranous nephropathy (OR 2.35, 95% CI 1.45-3.80), immunosuppressive therapy (OR 1.94, 95% CI 1.06-3.69), and ground glass opacity of CT scanning (OR 1.71, 95% CI 1.10-2.65) were associated with increased risk of Pneumocystis carinii infection. The AUC of nomogram based on logistics regression was 0.78 (0.75-0.81). The mortality in patients with PCP was 32.40%. Univariate analysis and decision tree showed that pulmonary insufficiency (PO2: OR 0.98, 95% CI 0.96-1.00), elevated APTT (OR 1.07, 95% CI 1.04-1.11), and reduced hemoglobin (OR 0.97, 95% CI 0.96-0.98) were associated with poor prognosis. PCP is not rare in CKD patients, particularly in those treated with immunosuppressive therapy. Considering the high mortality of the cases, further studies on the prevention and management of these patients are needed.

Epidemiological characteristics and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City / 中国血吸虫病防治杂志

Objective To investigate the prevalence and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City. Methods Children with diarrhea under 5 years of age admitted to Guangzhou Children’s hospital, Guangzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children’s Medical Center during the period between January 1 and December 31, 2020, were enrolled. Participants’ demographics, living environments and health status were collected using questionnaire surveys. Stool samples were collected from participants and nucleic acid was extracted. B. hominis infection was identified using PCR assay and sequence alignment, and the factors affecting B. hominis infection among children with diarrhea under 5 years of age were identified using univariate analysis and multivariate logistic regression analysis. Results A total of 684 children with diarrhea under 5 years of age were enrolled, including 468 male children and 216 female children, with a mean age of (1.79 ± 1.12) years. The overall prevalence of B. hominis infection was 4.97% [34/684, 95% confidential interval (CI): (3.59%, 6.86%)] among participants, and there was no significant difference in the prevalence of B. hominis infection between children with chronic [7.52% (20/266), 95% CI: (4.92%, 11.33%)] and acute diarrhea [3.35% (14/418), 95% CI: (2.01%, 5.54%)] (χ2 = 5.983, P = 0.014). Multivariate logistic regression analysis identified keeping pet [odds ratio (OR) = 6.298, 95% CI: (2.711, 14.633)], drinking non-tap water [OR = 4.522, 95% CI: (1.769, 11.561)], lactose intolerance [OR = 4.221, 95% CI: (1.043, 17.087)], antibiotic use [OR = 0.125, 95% CI: (0.017, 0.944)] and chronic diarrhea [OR = 2.172, 95% CI: (1.018, 4.637)] as factors affecting B. hominis infection among children with diarrhea under 5 years of age in Guangzhou City. Conclusions B. hominis infections is detected in children with diarrhea under five years of age in Guangzhou City. Improving home environments and pet-keeping hygiene is recommended to reduce the likelihood of B. hominis infection among children.

Analysis of current status and risk of development in occupational medical examination institutions in Guangdong Province / 中国职业医学

Objective: To analyze the status of occupational medical examination (OME) institutions in Guangdong Province and the critical control points affecting their future development. Methods: A total of 211 OME institutions registered in Guangdong Province were selected as the research subjects. Their current statue was investigated, and the risk assessment of their future development was carried out based on hazard analysis and critical control point theory. Results: The OME institutions were mainly concentrated in the Pearl River Delta, accounting for 72.0%. The public and private medical and health institutions accounted for 70.6% and 29.4% respectively. The filing rates of different OME categories from high to low in the order were physical factors, chemical factors, dust, other, radiation factors, biological factors (P<0.01), and the filing rates were 89.6%, 88.6%, 84.8%, 63.0%, 7.1% and 1.0%, respectively. The rates of excellence in the field assessment from high to low in the order were hearing atlas analysis personnel, lung function examination operators, chest film reading personnel, chief examination physician, technical director, quality director (P<0.01), and the rates of excellence were 49.4%, 26.2%, 20.6%, 10.8%, 8.2% and 4.6%, respectively. A total of 37 institutions did not submit OME information, of which 23 institutions did not carry out OME work after filing. The required diagnosis rate and confirmed diagnosis rate of suspected occupational diseases in 2020 were 34.3% and 55.3%, respectively. In 2021, the detection rate of suspected occupational diseases was only 1.1‰. Among the institutions with biological monitoring records, 64.1% did not participate in external quality assessment program in laboratory, and the unqualified rate of 38 participating institutions was 55.3%. The risk assessment results show that the future development of OME institutions needs to focus on private institutions, institutions that have not reported OME information, institutions that have missed diagnosis and missed reporting of suspected occupational diseases, institutions that have not participated in external quality assessment program in laboratory and core personnel such as quality managers, technical leaders, and main inspection physicians. Conclusion: OME institutions in Guangdong Province show the characteristics of centralized filing category, centralized filing region and centralized filing institution nature. Combined with the potential risks of OME institutional capacity building, it is necessary to implement classified management, strengthen information construction, supervision and management, implement post responsibilities, and promote the high-quality development of OME institutions.

Effects of Long-acting Injectable 3-Monthly Paliperidone Palmitate on the Clinical and Social Performance of Patients with Schizophrenia

Objective@#To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. @*Methods@#This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. @*Results@#The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p ＜ 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71−100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p＜ 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p＜ 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p ＜ 0.001; McNemar-Bowker test). @*Conclusion@#Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.

Establishment and evaluation of in vitro galectin-3 inhibitor screening model / 药学学报

Galectin-3 (Gal-3) belongs to the galectin family and is specific in binding β-galactoside. Through its C-terminal domain, Gal-3 binds to the galactoside group of the glycosylated insulin receptor (IR) and inhibits IR signaling pathway, which leads to the insulin resistance. Thus, Gal-3 is a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. Here we report a simple Gal-3 screening model based on the property that Gal-3 binds to the galactoside. We expressed and purified human Gal-3 in Escherichia coli (E.coli), and labeled it with fluorescein isothiocyanate (FITC) in vitro. After incubating FITC labeled Gal-3 (Gal-3-FITC) with PANC-1 cells, which express glycosylated membrane protein, PANC-1 cells started to show green fluorescent signal due to the Gal-3-FITC binding to the glycosylated membrane protein. Gal-3 inhibitor disrupts the binding of Gal-3-FITC and PANC1 cells, subsequently leads to the decrease of the fluorescent signal in PANC-1 cells. We can evaluate the inhibitory efficiency of Gal-3 inhibitors through measurement of the fluorescent signal. Further studies show this model is simple, stable, and repeatable with a Z' factor between 0.7 and 0.85. In sum, we have successfully established an in vitro high-throughput screening model for Gal-3 inhibitors.

Quality control of the technology method of clinical comprehensive drug evaluation / 中国药房

At present， there are still some problems in China’s clinical comprehensive drug evaluation， such as the unscientific design of the evaluation content， the nonstandard evaluation method and organizational process， and the evaluation results not meeting the decision-making needs. It is urgent to carry out quality control over the whole process of the clinical comprehensive drug evaluation project. From the technical point of view， the quality control methods of clinical comprehensive drug evaluation are discussed through three links of the evaluation content and design （giving the quality control key points of the theme selection process and scheme design）， the evaluation method （discussing the quality control elements of two common evaluation methods， i. e. documentary evidence method and real-world research） and result application transformation （giving suggestions on quality control from the comprehensive analysis of evaluation results， transformation of evaluation results and decision-making）， so as to promote the quality improvement of clinical comprehensive drug evaluation.

Acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy based on data mining technology / 中国针灸

OBJECTIVE@#To analyze the acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy by data mining technology.@*METHODS@#The literature regarding acupuncture and moxibustion for post-stroke epilepsy included in CNKI, VIP, Wanfang, SinoMed and PubMed databases from the establishment of the database to August 1st 2022 was retrieved. Microsoft Excel 2019 software was used to establish a database to conduct the descriptive analysis of acupoints; SPSS Modeler 18.0 Apriori algorithm was used to conduct association rule analysis; high-frequency acupoint co-occurrence network diagrams were drawn by Cytoscape3.9.0 software; SPSS Statistics 25.0 software was used to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn.@*RESULTS@#Totally 39 articles were included, and 63 prescriptions of acupuncture and moxibustion were extracted, involving 56 acupoints, with a total frequency of 516 times; the top three acupoints with the highest frequency of use were Baihui (GV 20), Fenglong (ST 40) and Neiguan (PC 6); the selected meridians were mainly the governor vessel, the hand and foot yangming meridians; the selection of acupoints were mostly in the head, neck and lower limbs; in terms of acupoint compatibility, Hegu (LI 4)-Shuigou (GV 26) and Neiguan (PC 6) had the highest confidence degree; The top 20 high-frequency acupoints could be divided into 4 effective clusters.@*CONCLUSION@#Modern acupuncture and moxibustion treatment for post-stroke epilepsy attaches great importance to the use of yang meridians and meridians with enrich qi and blood; the core prescription is Shuigou (GV 26)-Neiguan (PC 6)-Hegu (LI 4)-Baihui (GV 20). In addition, the combination of distant and near acupoints is highly valued to improve clinical efficacy.

Construction of drug clinical comprehensive evaluation index system and quantitative grading by using analytic hierarchy model / 中国药房

OBJECTIVE To construct the drug clinical comprehensive evaluation index system and quantitative grading in China， and to provide a reference for scientifically carrying out comprehensive clinical evaluation of drugs. METHODS The analytic hierarchy model was used to establish the drug clinical comprehensive evaluation index system， the weight of the evaluation index and the quantitative grading of each index were determined through expert consultation and model calculation. RESULTS The results of expert consultation were integrated by using the analytic hierarchy model， and the drug clinical comprehensive evaluation index system was obtained： including six first-level indicators of effectiveness， safety， economy， suitability， accessibility and innovation， as well as twenty-three second-level indicators of recommended status， medication for special populations， and drug treatment costs； the weight of each indicator was calculated through estimation-matrix method. CONCLUSIONS The analytic hierarchy model can construct the drug clinical comprehensive evaluation index system and quantitative grading in China， which can provide methodological references for comprehensive analysis and decision-making， thus making the clinical comprehensive evaluation of drugs completer and more scientific.

Distribution characteristics of newly reported occupational welder′s pneumoconiosis in Guangdong Province, 2013-2022 / 中国职业医学

Objective To analyze the distribution features of newly reported cases of occupational welder′s pneumoconiosis (OWP) in Guangdong Province from 2013 to 2022. Methods Data of newly reported cases of OWP from National Occupational Disease Network Direct Reporting System of Guangdong Province from 2013 to 2022 was analyzed using conventional data analyzing Methods. Results A total of 294 cases of OWP were reported in Guangdong Province from 2013 to 2022 with an overall downward trend. The average age at diagnosis for new OWP cases was 44±6 years old, and the median of dust exposure duration was 11 years. Males accounted for 99.3% of the cases, and 94.2% of the cases were phase Ⅰ OWP. Guangzhou City had the highest regional distribution with 74.8% of the cases. The industry distribution was mainly manufacturing, accounting for 86.7% of the cases. The scale of enterprises was most common in small enterprises, followed by large and medium-sized enterprises, accounting for 38.4%, 30.6% and 24.5% of the cases respectively. The economic types of enterprises were mostly private enterprises, followed by state-owned enterprises, accounting for 54.1% and 32.0% of the cases respectively. Conclusion In Guangdong Province, the newly reported OWP cases were clustered in terms of disease stage, regional distribution, industry, enterprise scale and enterprise economic type. There was a tendency of younger age at diagnosis and shorter dust exposure duration.

Comparative study on the methods to determine disintegration time of oral soluble films / 药学学报

Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films. At present, there is no standard method to determine the disintegration time of oral soluble films. In this study, we compared the six methods (pharmacopoeial disintegration method, petri dish method, sponge surface method, slide frame and ball method, partially immersed into liquid (without weight attached) and partially immersed into liquid (with weight attached)) to determine the in vitro disintegration time of oral soluble films with different thickness, and evaluated the correlation with the in vivo disintegration time. The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method (with weight attached) were excellent, with the endpoint of disintegration testing easy to determine. Partially immersed into liquid method (with weight attached), properly simulating the physiological condition in oral cavity, showed strong operability, good repeatability and in vitro-in vivo correlation, and was suitable for in vitro disintegration evaluation of oral soluble film dosage form. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Efficacy of W-genioplasty on the broad and short chin / 中华医学美学美容杂志

Objective:To investigate the clinical effect of W-shaped genioplasty in the correction of broad and short chin deformity.Methods:Thirty-eight patients (5 males, 33 females, aged 20 to 41 years, mean 27.3 years) complained with broad and short chin were admitted to the Affiliated Friendship Plastic Surgery Hospitalof Nanjing Medical University from January 2019 to December 2021. CBCT scan and three-dimensional reconstruction were performed to design osteotomy line and determine the distance of chin lengthening, narrowing and advancing or retrocession preoperatively. Under general anesthesia, the W-shaped osteotomy was performed using an intraoral incision, and the angle between the bilateral free bone fragments, the distance of downward and forward movement were adjusted to change the curvature, width, length and prominence of the lower edge of the chin according to the preoperative designs. The results were evaluated by clinical appearances and image analyses at a follow-up of 3-24 months.Results:The amount of vertical lengthening of the chin in 38 cases were 2 mm to 5 mm, with an average of 3.02 mm. The horizontal narrowing width distances were 3-7 mm, with an average of 5.6 mm. The patients were followed up for 3-24 months, with an average of 10.6 months. There were no complications such as hematoma, wound dehiscence, accidental fracture, surgical area infection and permanent neurosensory disorder. 38 patients had transient sensory loss in the lower lip region of varying degrees, but all recovered spontaneously during routine follow-up period. All patients were satisfied with the improvement of facial contour.Conclusions:W-shaped geinoplasty preserves the central bone of the chin and the attachment of genioglossus muscle, which does not affect the normal anatomy and physiological function of the oral cavity. After osteotomy, the bone is removed and the bilateral bone fragments move flexibly. It can effectively change the radian, width, length and protrusion of the lower edge of the chin in three dimensions, so as to correct the wide and short deformity of the chin.

Signal transducer and activator of transcription 6 mediates skeletal muscle cell injury in septic mice by regulating ferroptosis / 中华危重病急救医学

Objective:To explore the effect of signal transducer and activator of transcription 6 (STAT6) on ferroptosis in skeletal muscle cells in sepsis model and its potential mechanism.Methods:Twenty-four 8-week-old male specific pathogen free Kunming mice were divided into normal control group, sham group, sepsis model group and STAT6 inhibitor pretreatment group according to random number table method with 6 mice in each group. A mouse sepsis model was reproduced by cecal ligation and perforation (CLP). In the sham group, the skin of mice was sutured after exposing the cecum tissue. In the STAT6 inhibitor pretreatment group, 10 mg/kg AS1517499 was injected intraperitoneally 1 hour before model reproduction. The sham group and the model group were intraperitoneally injected with the same volume of normal saline. Mice in the normal control group did not receive any operation or drug intervention. The mice were sacrificed 24 hours after model reproduction, and the muscle tissue of hind limb was obtained under sterile condition. Hematoxylin-eosin (HE) staining was used to observe the histopathology with optical microscope, and mitochondrial morphological changes were observed by transmission electron microscopy after double staining with uranium acetate lead citrate. The ferroptosis marker proteins expressions of chitinase-3-like protein 1 (CHI3L1), cyclooxygenase-2 (COX-2), acyl-CoA synthetase long-chain family member 4 (ACSL4), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPx4) were detected by Western blotting.Results:Under the optical microscope, the morphology and structure of skeletal muscle tissues in the normal control and sham groups were normal. In the model group, the structure of skeletal muscle tissues was loose, the muscle fiber became smaller and atrophic, inflammatory cell infiltration and even muscle fiber loss were found. Compared with the model group, the structure of skeletal muscle tissues was tight and skeletal muscle atrophy was improved in the STAT6 inhibitor pretreatment group. The ultrastructure of skeletal muscle cell in the normal control and sham groups was normal under transmission electron microscope. The ultrastructure characteristics of skeletal muscle in the model group showed that cell membrane was broken and blister, mitochondria became smaller and membrane density increased, the mitochondrial crista decreased or disappeared, the mitochondrial outer membrane was broken, and the nucleus was normal in size but lacked chromatin condensation. Compared with the model group, the STAT6 inhibitor pretreatment group had a significant improvement in the ultrastructure of muscle cells. Compared with the normal control and sham groups, the protein expressions of CHI3L1, COX-2, ACSL4 and FTH1 in the muscle of the model group were significantly increased, while the protein expression of GPx4 was decreased significantly, indicating that the skeletal muscle cells in the mouse sepsis model showed characteristic mitochondrial injury and abnormal expression of ferroptosis markers. Compared with the model group, the protein expressions of CHI3LI, COX-2, ACSL4 and FTH1 in the STAT6 inhibitor pretreatment group were significantly decreased [CHI3L1 protein (CHI3L1/GAPDH): 0.70±0.08 vs. 0.97±0.09, COX-2 protein (COX-2/GAPDH): 0.61±0.03 vs. 0.83±0.03, ACSL4 protein (ACSL4/GAPDH): 0.75±0.04 vs. 1.02±0.16, FTH1 protein (FTH1/GAPDH): 0.49±0.06 vs. 0.76±0.13, all P < 0.05], while the protein expression of GPx4 was significantly increased (GPx4/GAPDH: 1.14±0.29 vs. 0.53±0.03, P < 0.05). Conclusions:Sepsis can induce ferroptosis in skeletal muscle cells of mice. STAT6 may mediate ferroptosis in mouse skeletal muscle cells by regulating the expressions of COX-2, ACSL4, FTH1 and GPx4, thereby inducing skeletal muscle cell injury in sepsis.

The "obesity paradox" in patients with atrial fibrillation: Insights from the Gulf SAFE registry.

Background: The prognostic impact of obesity on patients with atrial fibrillation (AF) remains under-evaluated and controversial. Methods: Patients with AF from the Gulf Survey of Atrial Fibrillation Events (Gulf SAFE) registry were included, who were recruited from six countries in the Middle East Gulf region and followed for 12 months. A multivariable model was established to investigate the association of obesity with clinical outcomes, including stroke or systemic embolism (SE), bleeding, admission for heart failure (HF) or AF, all-cause mortality, and a composite outcome. Restricted cubic splines were depicted to illustrate the relationship between body mass index (BMI) and outcomes. Sensitivity analysis was also conducted. Results: A total of 1,804 patients with AF and recorded BMI entered the final analysis (mean age 56.2 ± 16.1 years, 47.0% female); 559 (31.0%) were obese (BMI over 30 kg/m2). In multivariable analysis, obesity was associated with reduced risks of stroke/systematic embolism [adjusted odds ratio (aOR) 0.40, 95% confidence interval (CI), 0.18-0.89], bleeding [aOR 0.44, 95%CI, 0.26-0.74], HF admission (aOR 0.61, 95%CI, 0.41-0.90) and the composite outcome (aOR 0.65, 95%CI, 0.50-0.84). As a continuous variable, higher BMI was associated with lower risks for stroke/SE, bleeding, HF admission, all-cause mortality, and the composite outcome as demonstrated by the accumulated incidence of events and restricted cubic splines. This "protective effect" of obesity was more prominent in some subgroups of patients. Conclusion: Among patients with AF, obesity and higher BMI were associated with a more favorable prognosis in the Gulf SAFE registry. The underlying mechanisms for this obesity "paradox" merit further exploration.

Identification of mite-specific eosinophils in the colon of patients with ulcerative colitis.

The pathogenesis of ulcerative colitis (UC) is unclear. House dust mite (HDM) is associated with immune inflammation in the body. This study is designed to identify the association between HDM and UC clinical symptoms. UC patients (n = 86) and non-UC control (NC) subjects (n = 64) were recruited. Colon lavage fluids (CLF) were collected from HDM skin prick test positive patients during colonoscopy, and analyzed by immunological approaches. HDM was detected in fecal samples, which was positively correlated with UC clinical symptoms. HDM-specific eosinophils and Th2 cells were detected in CLF, which could be specifically activated by exposing to HDM in the culture. Direct exposure to HDM induced eosinophil activation in the colon of UC patients. UC patients displayed elevated levels of Th2 cytokines in the serum. UC clinical symptom scores were positively correlated with serum levels of Th2 cytokines. HDM was detected in UC patients' stools, which was positively correlated with UC clinical symptoms. Direct exposure to HDM could trigger eosinophilic activation of the colon.

Deoxyelephantopin alleviates lipopolysaccharide-induced septic lung injury through inhibiting NF-kB/STAT3 axis

Sepsis induces multiple organ dysfunction syndromes, such as acute kidney, liver, or lung injury. Septic lung injury is associated with excessive apoptosis and inflammatory responses in hepatocytes. Deoxyelephantopin is a sesquiterpene lactone found in Elephantopus scaberL, and has immunomodulatory, antibacterial, anti-inflammatory, and antifungal properties. The role of deoxyelephantopin in sepsis-associated lung injury was investigated. First, human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) were treated with lipopolysaccharide to induce cytotoxicity. Treatment with lipopolysac-charide reduced cell viability of BEAS-2B and HPAEC, and promoted cell apoptosis through down-regulation of poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma 2 (Bcl-2), and up-regulation of cleaved PARP and B-cell lymphoma-associated X protein (Bax). Second, lipo-polysaccharide-treated BEAS-2B and HPAEC were incubated with increasing concentrations of deoxyelephantopin, that is, 1, 5, or 10 μM. Deoxyelephantopin enhanced cell viability and reduced cell apoptosis of lipopolysaccharide-treated BEAS-2B and HPAEC. Third, deoxyele-phantopin attenuated lipopolysaccharide-induced decrease of superoxide dismutase and glutathione, and increase of malondialdehyde and myeloperoxidase in BEAS-2B and HPAEC. Moreover, deoxyelephantopin also weakened lipopolysaccharide-induced increase of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, deoxyelephantopin decreased pro-tein expression of p-p65 and p-signal transducer and activator of transcription 3 (STAT3) in lipopolysaccharide-treated BEAS-2B and HPAEC. In conclusion, deoxyelephantopin exhibited anti-oxidative and anti-inflammatory effects against lipopolysaccharide-treated BEAS-2B and HPAEC through inactivation of nuclear factor kappa B/STAT3 signaling (AU)

Sources and migration similarly determine nitrate concentrations: Integrating isotopic, landscape, and biological approaches.

Rapid land use change has significantly increased nitrate (NO3-) loading to rivers, leading to eutrophication, and posing water security problems. Determining the sources of NO3- to waters and the underlying influential factors is critical for effectively reducing pollution and better managing water resources. Here, we identified the sources and influencing mechanisms of NO3- in a mixed land-use watershed by integrating stable isotopes (δ15N-NO3- and δ18O-NO3-), molecular biology, water chemistry, and landscape metrics measurements. Weak transformation processes of NO3- were identified in the river, as evinced by water chemistry, isotopes, species compositions, and predicted microbial genes related to nitrogen metabolism. NO3- concentrations were primarily influenced by exogenous inputs (i.e., from soil nitrogen (NS), nitrogen fertilizer (NF), and manure & sewage (MS)). The proportions of NO3- sources seasonally varied. In the wet season, the source contributions followed the order of NS (38.6 %) > NF (31.4 %) > atmospheric deposition (ND, 16.2 %) > MS (13.8 %). In the dry season, the contributions were in the order of MS (39.2 %) > NS (29.2 %) > NF (29 %) > ND (2.6 %). Farmland and construction land were the original factors influencing the spatial distribution of NO3- in the wet and dry seasons, respectively, while slope, basin relief (HD), hypsometric integral (HI), and COHESION, HD were the primary indicators associated with NO3- transport in the wet and dry seasons, respectively. Additionally, spatial scale differences were observed for the effects of landscape structure on NO3- concentrations, with the greatest effect at the 1000-m buffer zone scale in the wet season and at the sub-basin scale in the dry season. This study overcomes the limitation of isotopes in identifying nitrate sources by combining multiple approaches and provides new research perspectives for the determination of nitrate sources and migration in other watersheds.

Identification of Hub Genes and Immune-Related Pathways for Membranous Nephropathy by Bioinformatics Analysis.

OBJECTIVE: We aim to explore the detailed molecular mechanisms of membrane nephropathy (MN) related genes by bioinformatics analysis. METHODS: Two microarray datasets (GSE108109 and GSE104948) with glomerular gene expression data from 65 MN patients and 9 healthy donors were obtained from the Gene Expression Omnibus (GEO) database. After processing the raw data, DEGs screening was conducted using the LIMMA (linear model for microarray data) package and Gene set enrichment analysis (GSEA) was performed with GSEA software (v. 3.0), followed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) network analysis was carried out to determine the hub genes, by applying the maximal clique centrality (MCC) method, which was visualized by Cytoscape. Finally, utilizing the Nephroseq v5 online platform, we analyzed subgroups associated with hub genes. The findings were further validated by immunohistochemistry (IHC) staining in renal tissues from MN or control patients. RESULTS: A sum of 370 DEGs (188 up-regulated genes, 182 down-regulated genes) and 20 hub genes were ascertained. GO and KEGG enrichment analysis demonstrated that DEGs of MN were preponderantly associated with cell damage and complement cascade-related immune responses. Combined with literature data and hub gene-related MN subset analysis, CTSS, ITGB2, and HCK may play important roles in the pathological process of MN. CONCLUSION: This study identified novel hub genes in MN using bioinformatics. We found that some hub genes such as CTSS, ITGB2, and HCK might contribute to MN immunopathological process, providing new insights for further study of the molecular mechanisms underlying glomerular injury of MN.