Effect of intravenous thrombolysis before endovascular therapy on outcomes in acute ischemic stroke with large core: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of intravenous thrombolysis (IVT) before endovascular therapy (EVT) on outcomes in acute ischemic stroke of large core. METHODS: The studies comparing functional outcomes after EVT with and without IVT were systematically searched up to October 10th, 2023. Odds ratio (OR) was pooled using random effects model. Subgroup analysis was performed stratified by study design, country or region, study date, imaging methods and time window. RESULTS: Thirteen studies were included, enrolling 1717 patients. The pooled rate of functional independence in patients receiving IVT + EVT was 26% (95% CI 20% - 33%), significantly higher than 18% (95% CI 15% - 20%) in those receiving EVT alone (OR 1.55, 95% CI 1.13-2.12, P = 0.006; I²= 23.9%). In subgroup analysis, prior IVT increased the probability of functional independence in retrospective studies (OR 1.97, 95% 1.47-2.63, P < 0.00001; I2 = 0). Non-Asian patients benefit from IVT before EVT for functional independence (OR 2.04, 95% 1.48-2.81, P < 0.0001; I2 = 0), but Asian patients did not (OR 1.45, 95% 0.90-2.35, p = 0.13; I2 = 0). The pooled rate of symptomatic intracranial hemorrhage in patients receiving IVT + EVT was 16% (95% CI 12% - 20%), inclining to be higher than 11% (95% CI 6% - 15%) in those receiving EVT alone without significant difference (OR 1.42, 0.83-2.41, P = 0.20; I²= 12%). CONCLUSIONS: IVT before EVT might increase the probability of functional independence in non-Asian patients with large ischemic core. The results provided clinicians with additional information on selecting eligible patients for EVT.

Reliability of the evidence to guide decision-making in the treatment of gastroesophageal reflux disease with acupuncture: protocol for an overview of systematic reviews.

BACKGROUND: Growing numbers of randomized clinical trials-based systematic reviews and meta-analyses (SRs/MAs) have been conducted to examine the effectiveness of acupuncture in treating gastroesophageal reflux disease (GERD). An overview of SRs/MAs will be conducted with the aim of systematically compiling, evaluating, and synthesizing the evidence regarding acupuncture for GERD. METHODS: SRs/MAs of acupuncture on GERD will be searched in eight databases. Two independent reviewers will conduct the literature search, data extraction, and review quality assessment. Utilizing the AMSTAR-2 tool, PRISMA checklists, and GRADE system, respectively, the methodological quality, reporting quality, and evidence quality will be evaluated. In relation to the subject and the overview's objects, the results will be given. This study will aid in identifying gaps between evidence and its clinical application and serve as a roadmap for further high-quality research. DISCUSSION: The results of the overview will aid in closing the gap between clinical evidence and its use in clinical practice. This study will identify significant faults in the use of evidence, point out areas where methodology needs to be improved, and provide guidance for future high-quality research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022371850. ETHICS AND DISSEMINATION: Ethics approval is not necessary because no personal information about individuals is collected. A peer-reviewed journal or pertinent conferences will publish the results, whichever comes first.

Exploring amyotrophic lateral sclerosis patients' experiences of psychological distress during the disease course in China: a qualitative study.

OBJECTIVE: This study aims to explore the psychological distress course of Chinese amyotrophic lateral sclerosis (ALS) patients after the onset of the disease and to provide targeted nursing guidance. DESIGN: The interview content was analysed qualitatively. We used seven steps of Colaizzi's method to analyse the participants' data. SETTING: Wuhan, China, Traditional Chinese Medicine Hospital. PARTICIPANTS: A semistructured face-to-face interview were performed among 22 people with ALS from the motor neuron disease rehabilitation centre of a tertiary Chinese medicine hospital in China. RESULT: This study included a total of 22 participants, from whom three main themes regarding the psychological distress trajectory of ALS patients were extracted from the interview data: 'Time begins to run out' include tormented and restless waiting and shock and doubt in ALS disease confirmation, 'Family out of control' include the burden of stigma and function loss, the burden of missing family roles, the burden of marriage's emotional needs and the burden of offspring health, 'Way forward' include struggle between live and death and struggle between quality of life and the value of life. CONCLUSION: This study outlines the psychologically distressing journey of ALS patients. Studies have pointed out the need for targeted care to address patients' various sources of psychological distress to improve their quality of life and coping ability, increase their psychological resilience and reconstruct their life beliefs.

π-Diamond: A Diamondoid Superstructure Driven by π-Interactions.

Modulating the arrangement of superstructures through noncovalent interactions has a significant impact on macroscopic shape and the expression of unique properties. Constructing π-interaction-driven hierarchical three-dimensional (3D) superstructures poses challenges on account of limited directional control and weak intermolecular interactions. Here we report the construction of a 3D diamondoid superstructure, named π-Diamond, employing a ditopic strained Z-shaped building block comprising a porphyrin unit as bow-limb double-strapped with two m-xylylene units as bowstring. This superstructure, reminiscent of diamond's tetrahedral carbon composition, is composed of double-walled tetrahedron (DWT) driven solely by π-interactions. Hetero-π-stacking between porphyrin and m-xylylene panels drive the assembly of four building blocks predominantly into a DWT, which undergoes extension to create an adamantane unit and eventually a diamondoid superstructure wherein each porphyrin panel is shared by two neighboring tetrahedra through hetero-π-stacking. π-Diamond exhibits a solid-state fluorescent quantum yield 44 times higher than that of tetraphenylporphyrin along with excellent photocatalytic performance. The precise 3D directionality of π-interactions, achieved through strained multipanel building blocks, revolutionizes the assembly of hierarchical 3D superstructures driven by π-interactions.

Recent Developments in Nanocomposite Membranes Based on Carbon Dots.

Carbon dots (CDs) have aroused colossal attention in the fabrication of nanocomposite membranes ascribed to their ultra-small size, good dispersibility, biocompatibility, excellent fluorescence, facile synthesis, and ease of functionalization. Their unique properties could significantly improve membrane performance, including permeance, selectivity, and antifouling ability. In this review, we summarized the recent development of CDs-based nanocomposite membranes in many application areas. Specifically, we paid attention to the structural regulation and functionalization of CDs-based nanocomposite membranes by CDs. Thus, a detailed discussion about the relationship between the CDs' properties and microstructures and the separation performance of the prepared membranes was presented, highlighting the advantages of CDs in designing high-performance separation membranes. In addition, the excellent optical and electric properties of CDs enable the nanocomposite membranes with multiple functions, which was also presented in this review.

Polystyrene nanoplastics induce cardiotoxicity by upregulating HIPK2 and activating the P53 and TGF-ß1/Smad3 pathways.

Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.

Adaptive designs were primarily used but inadequately reported in early phase drug trials.

BACKGROUND: Faced with the high cost and limited efficiency of classical randomized controlled trials, researchers are increasingly applying adaptive designs to speed up the development of new drugs. However, the application of adaptive design to drug randomized controlled trials (RCTs) and whether the reporting is adequate are unclear. Thus, this study aimed to summarize the epidemiological characteristics of the relevant trials and assess their reporting quality by the Adaptive designs CONSORT Extension (ACE) checklist. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to January 2020. We included drug RCTs that explicitly claimed to be adaptive trials or used any type of adaptative design. We extracted the epidemiological characteristics of included studies to summarize their adaptive design application. We assessed the reporting quality of the trials by Adaptive designs CONSORT Extension (ACE) checklist. Univariable and multivariable linear regression models were used to the association of four prespecified factors with the quality of reporting. RESULTS: Our survey included 108 adaptive trials. We found that adaptive design has been increasingly applied over the years, and was commonly used in phase II trials (n = 45, 41.7%). The primary reasons for using adaptive design were to speed the trial and facilitate decision-making (n = 24, 22.2%), maximize the benefit of participants (n = 21, 19.4%), and reduce the total sample size (n = 15, 13.9%). Group sequential design (n = 63, 58.3%) was the most frequently applied method, followed by adaptive randomization design (n = 26, 24.1%), and adaptive dose-finding design (n = 24, 22.2%). The proportion of adherence to the ACE checklist of 26 topics ranged from 7.4 to 99.1%, with eight topics being adequately reported (i.e., level of adherence ≥ 80%), and eight others being poorly reported (i.e., level of adherence ≤ 30%). In addition, among the seven items specific for adaptive trials, three were poorly reported: accessibility to statistical analysis plan (n = 8, 7.4%), measures for confidentiality (n = 14, 13.0%), and assessments of similarity between interim stages (n = 25, 23.1%). The mean score of the ACE checklist was 13.9 (standard deviation [SD], 3.5) out of 26. According to our multivariable regression analysis, later published trials (estimated ß = 0.14, p < 0.01) and the multicenter trials (estimated ß = 2.22, p < 0.01) were associated with better reporting. CONCLUSION: Adaptive design has shown an increasing use over the years, and was primarily applied to early phase drug trials. However, the reporting quality of adaptive trials is suboptimal, and substantial efforts are needed to improve the reporting.

Comparison of trait and state mind wandering among schizotypal, subclinically depressed, and control individuals.

BACKGROUND: Mind wandering is a common phenomenon in daily life. However, the manifestations and cognitive correlates of mind wandering in different subclinical populations remain unclear. In this study, these aspects were examined in individuals with schizotypal traits and individuals with depressive symptoms, i.e., subclinical populations of patients with schizophrenia and depression. METHODS: Forty-two individuals with schizotypal traits, 42 individuals with subclinical depression, and 42 controls were recruited to complete a mind wandering thought sampling task (state level) and a mind wandering questionnaire (trait level). Measures of rumination and cognitive functions (attention, inhibition, and working memory) were also completed by participants. RESULTS: Both subclinical groups exhibited more state and trait mind wandering than did the control group. Furthermore, individuals with schizotypal traits demonstrated more trait mind wandering than individuals with subclinical depression. Rumination, sustained attention, and working memory were associated with mind wandering. In addition, mind wandering in individuals with subclinical depression can be accounted for by rumination or attention, while mind wandering in individuals with high schizotypal traits cannot be accounted for by rumination, attention, or working memory. CONCLUSIONS: The results suggest that individuals with high schizotypal traits and subclinical depression have different patterns of mind wandering and mechanisms. These findings have implications for understanding the unique profile of mind wandering in subclinical individuals.

Thoracic high resolution computed tomography evaluation of imaging abnormalities of 108 lung cancer patients with different pulmonary function.

PURPOSE: Preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) belong to lung function injury. PRISm is a precursor to COPD. We compared and evaluated the different basic information, imaging findings and survival curves of 108 lung cancer patients with different pulmonary function based on high resolution computed tomography (HRCT). METHODS: This retrospective study was performed on 108 lung cancer patients who did pulmonary function test (PFT) and thoracic HRCT. The basic information was evaluated: gender, age, body mass index (BMI), smoke, smoking index (SI). The following pulmonary function findings were evaluated: forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio. The following computed tomography (CT) findings were evaluated: appearance (bronchiectasis, pneumonectasis, atelectasis, ground-glass opacities [GGO], interstitial inflammation, thickened bronchial wall), diameter (aortic diameter, pulmonary artery diameter, MPAD/AD ratio, inferior vena cava diameter [IVCD]), tumor (volume, classification, distribution, staging [I, II, III, IV]). Mortality rates were calculated and survival curves were estimated using the Kaplan-Meier method. RESULTS: Compared with normal pulmonary function group, PRISm group and COPD group were predominantly male, older, smoked more, poorer lung function and had shorter survival time after diagnosis. There were more abnormal images in PRISm group and COPD group than in normal lung function group (N-C group). In PRISm group and COPD group, lung cancer was found late, and the tumor volume was larger, mainly central squamous carcinoma. But the opposite was true for the N-C group. The PRISm group and COPD group had significant poor survival probability compared with the normal lung function group. CONCLUSIONS: Considerable differences regarding basic information, pulmonary function, imaging findings and survival curves are found between normal lung function group and lung function injury group. Lung function injury (PRISm and COPD) should be taken into account in future lung cancer screening studies.

Plasmodium vivax serological exposure markers: PvMSP1-42-induced humoral and memory B-cell response generates long-lived antibodies.

Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.

Structural Brain Connectivity Guided Optimal Contact Selection for Deep Brain Stimulation of the Subthalamic Nucleus.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy in ameliorating the motor symptoms of Parkinson disease. However, postoperative optimal contact selection is crucial for achieving the best outcome of deep brain stimulation of the subthalamic nucleus surgery, but the process is currently a trial-and-error and time-consuming procedure that relies heavily on surgeons' clinical experience. METHODS: In this study, we propose a structural brain connectivity guided optimal contact selection method for deep brain stimulation of the subthalamic nucleus. Firstly, we reconstruct the DBS electrode location and estimate the stimulation range using volume of tissue activated from each DBS contact. Then, we extract the structural connectivity features by concatenating fractional anisotropy and the number of streamlines features of activated regions and the whole brain regions. Finally, we use a convolutional neural network with convolutional block attention module to identify the structural connectivity features for the optimal contact selection. RESULTS: We review the data of 800 contacts from 100 patients with Parkinson disease for the experiment. The proposed method achieves promising results, with the average accuracy of 97.63%, average precision of 94.50%, average recall of 94.46%, and average specificity of 98.18%, respectively. Our method can provide the suggestion for optimal contact selection. CONCLUSIONS: Our proposed method can improve the efficiency and accuracy of DBS optimal contact selection, reduce the dependence on surgeons' experience, and has the potential to facilitate the development of advanced DBS technology.

Dual-sensitized heterojunction Ag2S/ZnS/NiS composites with entire visible-light region absorption for ultrasensitive photoelectrochemical detection of tobramycin.

In this study, an ultrasensitive photoelectrochemical (PEC) aptasensor based on dual-sensitized heterojunction Ag2S/ZnS/NiS composites as a signal probe was proposed for the detection of tobramycin (TOB) by combining a cascaded quadratic signal amplification strategy. Specifically, compared to the limited visible light-harvesting capability of single sensitized composites, Ag2S/ZnS/NiS composites with p-n and n-n heterojunction could greatly improve the light energy utilization to tremendously strengthen the optical absorption in the entire visible-light region. Moreover, dual-sensitized heterojunction could effectively hinder the rapid recombination of photoelectrons and holes (carriers) to obtain a good photocurrent for improving the sensitivity of the aptasensor. Furthermore, a cascaded quadratic signal amplification strategy was applied to convert trace target TOB into plentiful gold nanoclusters (Au NCs) labelled double-stranded DNA for the construction of PEC aptasensor, with a broad linear detection range from 0.01 to 100 ng mL-1 and a low detection limit of 3.38 pg mL-1. Importantly, this study provided a versatile and sensitive PEC biosensing platform for TOB analysis, and demonstrated its successful application for TOB detection in milk samples. This protocol provides a novel dual-sensitized heterojunction composites to develop a highly efficient and harmfulless PEC aptasensor, which is expected to be used in food safety, environmental monitoring and other areas.

The energy metabolism of the freshwater leech Whitmania pigra in response to fasting.

Non-blood-feeding leeches, Whitmania pigra, have evolved unique digestive structures and physiological mechanisms to cope with fasting. However, the metabolic changes and molecular mechanisms induced by fasting remain unclear. Therefore, this study recorded the weights of leeches during the fasting process. The weight changes were divided into two stages: a rapid decline period (1-9 weeks) and a fluctuating decline period (9-24 weeks). Leeches fasted for 4 (H4), 11 (H11), and 24 (H24) weeks were selected for transcriptome sequencing. Compared to the control group (H0), 436, 1157, and 337 differentially expressed genes (DEGs) were identified, which were mainly related to glycolysis/gluconeogenesis, amino acid metabolism, and the lipid metabolism pathway. The 6-phosphofructokinase (Pfk), pyruvate kinase (PK), and phosphoenolpyruvate carboxykinase (Pck) transcription levels revealed glycolysis/gluconeogenesis activation during the early stage of fasting and peaked at 11 weeks. Decreased expression of the rate-limiting enzyme acetyl-CoA carboxylase (ACC) in fatty acid synthesis during fasting may impede fatty acid synthesis. These results indicated that the nutrient storage and energy-supplying pathways in W. pigra were modified to improve fasting resistance. The findings of this study provided guidance for exploring the mechanism underlying fasting metabolism and laid a foundation for artificial breeding to improve the resistance of leeches.

Single-Atom Iron Doped Carbon Dots with Highly Efficient Electrochemiluminescence for Ultrasensitive Detection of MicroRNAs.

Herein, single-atom iron doped carbon dots (SA Fe-CDs) were successfully prepared as novel electrochemiluminescence (ECL) emitters with high ECL efficiency, and a biosensor was constructed to ultrasensitively detect microRNA-222 (miRNA-222). Importantly, compared with the conventional without single-atom doped CDs with low ECL efficiency, SA Fe-CDs exhibited strong ECL efficiency, in which single-atom iron as an advanced coreactant accelerator could significantly enhance the generation of reactive oxygen species (ROS) from the coreactant S2O82- for improving the ECL efficiency. Moreover, a neoteric amplification strategy combining the improved strand displacement amplification with Nt.BbvCI enzyme-induced target amplification (ISDA-EITA) could produce 4 output DNAs in every cycle, which greatly improved the amplification efficiency. Thus, a useful ECL biosensor was built with a detection limit of 16.60 aM in the range of 100 aM to 1 nM for detecting traces of miRNA-222. In addition, miRNA-222 in cancer cell lysate (MHCC-97L) was successfully detected by using the ECL biosensor. Therefore, this strategy provides highly efficient single-atom doped ECL emitters for the construction of sensitive ECL biosensing platforms in the biological field and clinical diagnosis.

Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation.

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.

The Future-oriented Repetitive Thought (FoRT) scale: Validation in Chinese samples and application in the schizophrenia spectrum.

BACKGROUND: Repetitive thoughts are usually associated with psychopathology. The Future-oriented Repetitive Thought (FoRT) Scale is a measure designed to capture frequency of repetitive thought about positive and negative future events. However, the validity of the scale in Chinese population and its application in the schizophrenia spectrum have not been examined. METHODS: The current study aimed to examine the psychometric properties of the Chinese version of the FoRT scale and to apply it to the schizophrenia spectrum. In Study 1, three samples (total N = 1875) of university students were recruited for exploratory factor analysis, confirmatory factor analysis, and validity test, respectively. In Study 2, we identified subsamples with high schizotypal traits (N = 89) and low schizotypal traits (N = 89), and recruited 36 inpatients with schizophrenia and 41 matched healthy controls. RESULTS: The three-factor (pessimistic repetitive future thinking, repetitive thinking about future goals, and positive indulging about the future) structure of the FoRT scale with one item deleted, fitted the Chinese samples. And the scale could distinguish patients with schizophrenia and individuals with high schizotypal traits from controls. CONCLUSION: These findings support that the Chinese version of the FoRT scale is a valid tool and provide evidence for the potential applications in the schizophrenia spectrum.

Insights into effects of thermotolerant nitrifying and sulfur-oxidizing inoculants on nitrogen-sulfur co-metabolism in sewage sludge composting.

In this study, high temperature thermotolerant nitrifying bacteria (TNB) and high temperature thermotolerant sulfide oxidizing bacteria (TSOB) were obtained from compost samples and inoculated into sewage sludge (SS) compost. The effects of inoculation on physical and chemical parameters, ammonia and hydrogen sulfide release, nitrogen form and sulfur compound content change and physical-chemical properties during nitrogen and sulfur conversion were studied. The results showed that inoculation of TNB and TSOB increased the temperature, pH, OM degradation, C/N ratio and germination index (GI) of compost. Compared with the control treatment (CK), the addition of inoculants reduced the release of NH3 and H2S, and transformed them into nitrogen and sulfur compounds, the hydrolysis of polymeric ferrous sulfate was promoted, resulting in relatively high content of sulfite and sulfate. At the same time, the physical and chemical properties of SS have a strong correlation with nitrogen and sulfur compounds.

Total flavone of Abelmoschus manihot regulates autophagy through the AMPK/mTOR signaling pathway to treat intestinal fibrosis in Crohn's disease.

BACKGROUND AND AIM: Drug therapy is the treatment of choice for Crohn's disease because it effectively controls or prevents intestinal inflammation. The purpose was to research the molecular mechanism of the total flavones of Abelmoschus manihot (TFA) on intestinal fibrosis in Crohn's disease. METHODS: A 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model and IGF-1-treated intestinal fibroblasts were established. Then, TFA, 3-MA, and compound C were used treatments. Hematoxylin and eosin, Masson, and Picrosirius red staining were performed to observe the colon tissue. Immunohistochemical staining was used to detect α-SMA expression. Flow cytometry, CCK8, wound healing, and Transwell assays were conducted to determine apoptosis, proliferation, invasion, and migration. Col1a1 and Col3a1 levels were detected using quantitative polymerase chain reaction. Proteins related to autophagy and apoptosis were detected using western blotting. RESULTS: TFA treated intestinal fibrosis in chronic Crohn's disease. Colon length was the shortest in the ethanol + TNBS group, and TFA treatment significantly improved the situation. Intestinal fibrosis and the percentage of collagen area decreased after TFA treatment. TFA reduced fibrosis by enhancing autophagy stimulation, whereas an autophagy inhibitor reversed the TFA effect. TFA also inhibited migration, proliferation, and collagen synthesis in intestinal fibroblasts. Moreover, it enhanced autophagy and apoptosis of intestinal fibroblasts. TFA upregulated p-AMPK expression and decreases p-mTOR levels. Compound C partially rescued the effect of TFA, indicating that TFA affected intestinal fibroblasts via the AMPK/mTOR pathway in vitro and in vivo. TFA also downregulated Col1a1 and Col3a1 expression. CONCLUSION: TFA regulates autophagy through AMPK/mTOR signaling pathway to treat intestinal fibrosis, which may provide a new therapy for Crohn's disease treatment.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

A nomogram to predict cognitive function impairment in patients with chronic kidney disease: A national cross-sectional survey.

Background: Cognitive function impairment (CFI) is common in patients with chronic kidney disease (CKD) and significantly impacts treatment adherence and quality of life. This study aims to create a simplified nomogram for early CFI risk detection. Methods: Data were obtained from the National Health and Nutrition Examination Survey cycles spanning from 1999 to 2002 and again from 2011 to 2014. Stepwise logistic regression was used to select variables and construct a CFI risk prediction model. Furthermore, C-statistic and Brier Score (BS) assessed model performance. Additionally, Kaplan-Meier survival curves were utilised to assess risk group-death prognosis relationships. Results: Of the 545 participants in the CKD model development cohort, a total of 146 (26.8 %) had CFI. The final model included the variables of age, race, education, annual family income, body mass index, estimated glomerular filtration rate, serum albumin and uric acid. The model had a C-statistic of 0.808 (95 % confidence interval (CI): 0.769-0.847) and a BS of 0.149. Furthermore, the 5-fold cross-validation internal C-statistic was 0.764 (interquartile range: 0.763-0.807) and BS was 0.154. Upon external validation, the model's C-statistic decreased to 0.752 (95 % CI: 0.654-0.850) and its BS increased to 0.182. The Kaplan-Meier survival curves demonstrated that intermediate-to-high-risk participants had shorter overall survival time than low-risk participants (log-rank test: p = 0.00042). Conclusions: This study established an effective nomogram for predicting CFI in patients with CKD, which can be used for the early detection of CFI and guide the treatment of patients with CKD.