An observational and genetic investigation into the association between psoriasis and risk of malignancy.

The relationship between psoriasis and site-specific cancers remains unclear. Here, we aim to investigate whether psoriasis is causally associated with site-specific cancers. We use observational and genetic data from the UK Biobank, obtaining GWAS summary data, eQTL analysis data, TCGA data, and GTEx data from public datasets. We perform PheWAS, polygenic risk score analysis, and one-sample and two-sample Mendelian randomization analyses to investigate the potential causal associations between psoriasis and cancers. In the unselected PheWAS analysis, psoriasis is associated with higher risks of 16 types of cancer. Using one-sample Mendelian randomization analyses, it is found that genetically predicted psoriasis is associated with higher risks of anal canal cancer, breast cancer, follicular non-Hodgkin's lymphoma and nonmelanoma skin cancer in women; and lung cancer and kidney cancer in men. Our two-sample Mendelian randomization analysis indicates that psoriasis is causally associated with breast cancer and lung cancer. Gene annotation shows that psoriasis-related genes, such as ERAP1, are significantly different in lung and breast cancer tissues. Taken together, clinical attention to lung cancer and breast cancer may be warranted among patients with psoriasis.

A thaumatin-like effector protein suppresses the rust resistance of wheat and promotes the pathogenicity of Puccinia triticina by targeting TaRCA.

Thaumatin-like proteins (TLPs) in plants play a crucial role in combating stress, and they have been proven to possess antifungal properties. However, the role of TLPs in pathogens has not been reported. We identified a effector protein, Pt9029, which contained a Thaumatin domain in Puccinia triticina (Pt), possessing a chloroplast transit peptide and localized in the chloroplasts. Silencing Pt9029 in the Pt physiological race THTT resulted in a notable reduction in virulence and stunted growth and development of Pt hypha in near-isogenic wheat line TcLr2b. Overexpression of Pt9029 in wheat exerted a suppressive effect on H2O2 production, consequently impeding the wheat's disease resistance mechanisms. The TLP domain of Pt9029 targets the Rubisco activase (TaRCA) in chloroplasts. This interaction effectively inhibited the function of TaRCA, subsequently leading to a decrease in Rubisco enzyme activity. Therefore, this indicates that TLPs in Pt can inhibit host defense mechanisms during the pathogenic process of Pt. Moreover, TaRCA silencing resulted in reduced resistance of TcLr2b against Pt race THTT. This clearly demonstrated that TaRCA positively regulates wheat resistance to leaf rust. These findings reveal a novel strategy exploited by Pt to manipulate wheat rust resistance and promote pathogenicity.

Identification of symptomatic carotid artery plaque: a predictive model combining angiography with optical coherence tomography.

Objective: Symptomatic carotid artery disease is indicative of an elevated likelihood of experiencing a subsequent stroke, with the morphology of plaque and its specific features being closely linked to the risk of stroke occurrence. Our study based on the characteristics of carotid plaque assessed by optical coherence tomography (OCT), the plaque morphology evaluated by digital subtraction angiography (DSA) and clinical laboratory indicators were combined, develop a combined predictive model to identify symptomatic carotid plaque. Methods: Patients diagnosed with carotid atherosclerotic stenosis who underwent whole-brain DSA and OCT examination at the Affiliated Hospital of Jining Medical University from January 2021 to November 2023 were evaluated. Clinical features, as well as DSA and OCT plaque characteristics, were analyzed for differences between symptomatic and asymptomatic cohorts. An analysis of logistic regression was carried out to identify factors associated with the presence of symptomatic carotid plaque. A multivariate binary logistic regression equation was established with the odds ratio (OR) serving as the risk assessment parameter. The receiver operating characteristic curve was utilized to assess the combined predictive model and independent influencing factors. Results: A total of 52 patients were included in the study (symptomatic: 44.2%, asymptomatic: 55.8%). Symptomatic carotid stenosis was significantly linked to four main factors: low-density lipoprotein-cholesterol >3.36 mmol/L [OR, 6.400; 95% confidence interval (CI), 1.067-38.402; p = 0.042], irregular plaque (OR, 6.054; 95% CI, 1.016-36.083; p = 0.048), ruptured plaque (OR, 6.077; 95% CI, 1.046-35.298; p = 0.048), and thrombus (OR, 6.773; 95% CI, 1.194-38.433; p = 0.044). The combined predictive model generated using four indicators showed good discrimination (Area Under Curve, 0.924; 95% CI, 0.815-0. 979). The p value was <0.05 with 78.26% sensitivity and 93.10% specificity. Conclusion: OCT is valuable in evaluating the plaque characteristics of carotid atherosclerotic stenosis. The combined predictive model comprising low-density lipoprotein-cholesterol >3.36 mmol/L, irregular plaque, ruptured plaque, and thrombus could help in the detection of symptomatic carotid plaque. Further research conducted on additional independent cohorts is necessary to confirm the clinical significance of the predictive model for symptomatic carotid plaque.

Wheat Leaf Rust Fungus Effector Protein Pt1641 Is Avirulent to TcLr1.

Wheat leaf rust fungus is an obligate parasitic fungus that can absorb nutrients from its host plant through haustoria and secrete effector proteins into host cells. The effector proteins are crucial factors for pathogenesis as well as targets for host disease resistance protein recognition. Exploring the role of effector proteins in the pathogenic process of Puccinia triticina Eriks. (Pt) is of great significance for unraveling its pathogenic mechanisms. We previously found that a cysteine-rich effector protein, Pt1641, is highly expressed during the interaction between wheat and Pt, but its specific role in pathogenesis remains unclear. Therefore, this study employed techniques such as heterologous expression, qRT-PCR analysis, and host-induced gene silencing (HIGS) to investigate the role of Pt1641 in the pathogenic process of Pt. The results indicate that Pt1641 is an effector protein with a secretory function and can inhibit BAX-induced programmed cell death in Nicotiana benthamiana. qRT-PCR analyses showed that expression levels of Pt1641 were different during the interaction between the high-virulence strain THTT and low-virulence strains FGD and Thatcher, respectively. The highest expression level in the low-virulence strain FGD was four times that of the high-virulence strain THTT. The overexpression of Pt1641 in wheat near-isogenic line TcLr1 induced callose deposition and H2O2 production on TcLr1. After silencing Pt1641 in the Pt low-virulence strain FGD on wheat near-isogenic line TcLr1, the pathogenic phenotype of Pt physiological race FGD on TcLr1 changed from ";" to "3", indicating that Pt1641 plays a non-toxic function in the pathogenicity of FGD to TcLr1. This study helps to reveal the pathogenic mechanism of wheat leaf rust and provides important guidance for the mining and application of Pt avirulent genes.

Hydrological dynamics in the China-Mongolia arid region: An integrated analysis of precipitation recycling and water vapor conversion.

This study examines the atmospheric water cycle dynamics in the China-Mongolia Arid Region (CMAR), a region significantly affected by aridity. By employing a combination of Empirical Orthogonal Function (EOF) analysis, ERA5 reanalysis data, and the Dynamic Recycling Model (DRM), we investigate the spatial and temporal variations in the Precipitation Recycling Ratio (PRR) and Precipitable Water Conversion Rate (PWCR) over a forty-year period (1979-2021). Our findings reveal that both PRR and PWCR are generally higher but decreasing in most subregions of CMAR, suggesting a notable contribution of local moisture to precipitation. We also identify an increasing trend in PRR across the northwestern subregions and a decreasing trend in other areas. Similarly, PWCR exhibits an increasing trend in the northwestern and southern subregions, while decreasing elsewhere, implying a decline in water vapor conversion and recycling efficiency. Furthermore, our EOF analysis uncovers distinct spatial patterns, with dominant modes accounting for significant variances in PRR and PWCR, correlating with local variations in atmospheric moisture and advective changes. These results underscore the complex interplay between regional topography, atmospheric dynamics, and the hydrological cycle in CMAR. The insights from this study are vital for formulating effective water management strategies and adapting to climate change impacts in arid regions, holding broad implications for environmental science, climate studies, and sustainable resource management. Our findings reveal distinct spatial patterns and contrasting trends in precipitation recycling and water vapor conversion across the subregions of CMAR. This heterogeneity underscores the importance of conducting analyses at finer spatial scales to avoid contradictory conclusions that can arise from topographic influences when treating CMAR as a single unit. Future studies should focus on smaller subregions to accurately capture the intricacies of the water cycle in this topographically complex arid region.

Neutrophil extracellular traps promote macrophage inflammation in psoriasis.

Psoriasis is a chronic inflammatory skin disease connected with immune dysregulation. Macrophages are key inflammatory cells in psoriasis but the specific mechanism of their activation is not fully understood. Neutrophil extracellular traps (NETs) have been shown to regulate macrophage function. Here, we found that NET deposition was increased in psoriasis lesions. Peptidylarginine deaminase 4 (PAD4, a key enzyme for NET formation) deficiency attenuated skin lesions and inflammation in an imiquimod-induced psoriatic mouse model. Furthermore, the STING signaling pathway was markedly activated in psoriasis and abolished by PAD4 deficiency. PAD4-deficient mice treated with the STING agonist DMXAA exhibited more severe symptoms and inflammation than control mice. Mechanistically, the STING inhibitor C-176 inhibited NET-induced macrophage inflammation and further inhibited the proliferation of HaCaT cells. Our findings suggest an important role of NETs in the pathogenesis of psoriasis, and activation of macrophage STING/NF-κB signaling pathway might involve in NETs related psoriasis.

Association between BCL2 interacting protein 3 like (BNIP3L) genetic polymorphisms and the risk of multiple myeloma in China.

BACKGROUND: The BCL2 interacting protein 3-like (BNIP3L) protein is involved in multiple myeloma (MM) development and progression. This study aims to explore the connection between BNIP3L single-nucleotide polymorphisms (SNPs) and MM. METHODS: SNaPshot was used to examine six SNP loci of the BNIP3L gene in enrolled subjects. The relationship between these loci and MM susceptibility and prognosis was explored. Survival analysis was used to evaluate the impact of different factors on patient survival. RESULTS: The rs2874670 AA genotype and A allele were associated with increased MM risk (P < 0.05). The CCACAC haplotype had a higher frequency in MM, while CCGCAC had a higher frequency in normal patients (all P < 0.05). Patients with R-ISS stage I and II had higher survival rates than those with stage III (P < 0.05). Patients, who received chemotherapy followed by autologous stem cell transplantation, had longer survival time than those who only received chemotherapy (P < 0.05). Low levels of LDH and ß2-MG were associated with better survival rates (P < 0.05). Cox regression identified that LDH levels, ß2-MG levels, and R-ISS staging were the risk factors for the death of MM. Mann-Whitney U test found a significant difference in survival time between MM patients with different BNIP3L rs2874670 genotypes after BD chemotherapy (P < 0.05). CONCLUSION: To our knowledge, this is the first study to find that BNIP3L rs2874670 could increase MM susceptibility in China. Different BNIP3L rs2874670 genotypes may affect the prognosis of MM patients receiving BD chemotherapy.

Factors associated with perceived cognitive function in breast cancer patients treated with chemotherapy: A multicenter cross-sectional study.

PURPOSE: This study aimed to investigate the factors associated with perceived cognitive function among breast cancer patients treated with chemotherapy in China. METHODS: The study was a multicenter cross-sectional design. Data were collected from 10 public hospitals in China between April 2022 and February 2023. A total of 741 participants completed questionnaires assessing sociodemographic and medical characteristics, perceived cognitive function, sleep quality, fatigue, anxiety, and depression. Hierarchical multiple regression analysis was used to assess the determinants of cognitive function. RESULTS: The hierarchical multiple regression model accounted for 31.5% of variation in perceived cognitive function (sociodemographic 4.5%; medical 6.6%; exercise frequency 6.6%; sleep quality 2.1%; fatigue 2.8%; anxiety combined with depression 9.0%). Education level, chemotherapy type, number of chemotherapy cycles, and cyclophosphamide drug use were significant predisposing factors of perceived cognitive function (p < 0.001). Exercising ≥3 times/week (p < 0.001) was a significant factor positively influencing perceived cognitive function, meanwhile, anxiety (p < 0.001) and depression (p < 0 0.001) were negative factors. CONCLUSION: Our findings suggest that patients with low education levels, postoperative chemotherapy, cyclophosphamide treatment, and a greater number of chemotherapy cycles need more assessment. Sedentary patients, those who have never exercised, and those with anxiety or depression all showed greater cognitive decline. By identifying susceptible populations, encouraging regular exercise, and addressing anxiety and depression, healthcare professionals can contribute significantly to prevent patients' cognitive decline throughout chemotherapy.

The Impact of Artificial Restoration of Alpine Grasslands in the Qilian Mountains on Vegetation, Soil Bacteria, and Soil Fungal Community Diversity.

To understand how the soil microbial community structure responds to vegetation restoration in alpine mining areas, this study specifically examines the grassland ecosystem in the Qianmalong mining area of the Qilian Mountains after five years of artificial restoration. High-throughput sequencing methods were employed to analyze soil bacteria and fungi microbial characteristics in diverse grassland communities. Combined with modifications in vegetation diversity as well as soil physicochemical properties, the impact of vegetation restoration on soil microbiome diversity in this alpine mining area was investigated. The findings indicated that the dominant plants were Cyperus rotundus, Carex spp., and Elymus nutans. As the extent of the grassland's restoration increased, the number of plant species, importance values, and plant community diversity showed an increasing trend. The plant functional groups were mainly dominated by Cyperaceae, followed by Poaceae. Plant height, density, plant cover, frequency, and aboveground biomass showed an increasing trend, and soil water content (SWC) increased. While soil pH and soil electrical conductivity (EC) exhibited a declining trend, available phosphorus (AP), total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (NO3-N), soil organic carbon (SOC), and soil water content (SWC) showed an increasing trend. The dominant bacterial communities were Actinobacteriota, Proteobacteria, Acidobacteriota, Chloroflexi, Firmicutes, and Gemmatimonadota, while the dominant fungal communities were Ascomycota, Mortierellomycota, Basidiomycota, unclassified_k_Fungi, and Glomeromycota. Significant differences were detected within soil microbial community composition among different degrees of restoration grasslands, with bacteria generally dominating over fungi. SWC, TP, and TN were found to be the main soil physicochemical factors affecting the distribution of soil bacterial communities' structure; however, SOC, TN, and NO3-N were the primary factors influencing the soil distribution of fungal communities. The results of this study indicate that different degrees of vegetation restoration in alpine mining areas can significantly affect soil bacterial and fungal communities, and the degree of restoration has varying effects on the soil bacteria and fungi community structure in alpine mining areas.

Deciphering the formation of granules by n-DAMO and Anammox microorganisms.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process is a promising wastewater treatment technology, but the slow microbial growth rate greatly hinders its practical application. Although high-level nitrogen removal and excellent biomass accumulation have been achieved in n-DAMO granule process, the formation mechanism of n-DAMO granules remains unresolved. To elucidate the role of functional microbes in granulation, this study attempted to cultivate granules dominated by n-DAMO microorganisms and granules coupling n-DAMO with anaerobic ammonium oxidation (Anammox). After long-term operation, dense granules were developed in the two systems where both n-DAMO archaea and n-DAMO bacteria were enriched, whereas granulation did not occur in the other system dominated by n-DAMO bacteria. Extracellular polymeric substances (EPS) measurement indicated the critical role of EPS production in the granulation of n-DAMO process. Metagenomic and metatranscriptomic analyses revealed that n-DAMO archaea and Anammox bacteria were active in EPS biosynthesis, while n-DAMO bacteria were inactive. Consequently, more EPS were produced in the systems containing n-DAMO archaea and Anammox bacteria, leading to the successful development of n-DAMO granules. Furthermore, EPS biosynthesis in n-DAMO systems is potentially regulated by acyl-homoserine lactones and c-di-GMP. These findings not only provide new insights into the mechanism of granule formation in n-DAMO systems, but also hint at potential strategies for management of the granule-based n-DAMO process.

Case report: Novel NUS1 variant in a Chinese patient with tremors and intellectual disability.

Introduction: Nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) gene variants are associated with a range of phenotypes, including epilepsy, intellectual disability, cerebellar ataxia, Parkinson's disease, dystonia, and congenital disorders of glycosylation. Additionally, cases describing genotypes and clinical features are rare. Case Presentation: Herein, we report the case of a 23-year-old Chinese female patient who presented with tremors, intellectual disability, and epilepsy. A history of carbon monoxide exposure, brain trauma, or encephalitis was not present in this case. Trio whole-exome sequencing analysis revealed a de novo pathogenic variant of c.750del in exon 4, leading to p.Leu251* amino acid substitution. Genetic analysis failed to identify the identical mutations in the remaining family members who underwent screening. The patient was diagnosed with a rare congenital disease, "congenital glycosylation disorder, type 1aa, autosomal dominant, type 55, with seizures (MRD-55)." Conclusion: We provide further evidence for the role of variants in NUS1 in the development of tremors, epilepsy, and intellectual disabilities. These findings expand our understanding of the clinical phenotypes of NUS1 variants.

Construction and validation of a risk-prediction model for chemotherapy-related cognitive impairment in patients with breast cancer.

PURPOSE: To identify risk factors of chemotherapy-related cognitive impairment (CRCI) and construct and validate a visual prediction model of such for patients with breast cancer. METHODS: A multicenter, descriptive, and cross-sectional design was adopted. Data were collected from ten public tertiary hospitals in China. Cognitive function was assessed by using Functional Assessment of Cancer Therapy-cognitive function. Socio-demographic, clinical, psychological, and physical indicators were also assessed. The logistic prediction model was constructed by fivefold cross-validation. Then, a nomogram was utilized to visualize the prediction model, which was also evaluated via discrimination, calibration, and decision curve analysis. RESULTS: A total of 71 breast cancer patients had CRCI with a prevalence of 9.58%. This visual prediction model was constructed based on education background, exercise frequency, chemotherapy times, and fatigue and demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.882. The calibration curve indicated good agreement between experimental and projected values, and the decision curve proved good clinical applicability. CONCLUSION: Education background, exercise frequency, chemotherapy times, and fatigue were associated with high incidence of CRCI. The prediction model exhibits superior performance and has promise as a useful instrument for assessing the likelihood of CRCI in breast cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: Our findings could provide breast cancer survivors with risk screening based on CRCI predictors to implement prevention and early intervention, and help patients integrate into society and achieve comprehensive recovery.

Sepsis and multi-organ failure due to genital herpes in a healthy person.

Herpes simplex virus type 2 (HSV-2) is highly prevalent in several regions of the world and is the main pathogen causing genital herpes, which is transmitted almost exclusively through sexual contact. Systemically disseminated infections caused by HSV-2 are rare and most often seen in newborns, pregnant women, or immunocompromised populations. The virus can invade multiple organs and cause damage. In this paper, we present an extremely rare case of an immunocompetent 36-year-old male who came to our hospital with a high fever with abdominal pain and died of sepsis and multiple organ dysfunction syndrome within a short period. After the exclusion of common pathogens such as bacterial and fungal infections during hospitalization, metagenomic next generation sequencing of the patient's peripheral blood and ascites gave us the answer, and very high nucleic acid sequence counts of HSV-2 were detected in both his peripheral blood and ascites, confirming HSV-2 as the causative virus. In addition, this paper provides a brief review of the relevant literature.

Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study.

OBJECTIVES: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl-1/mIU∙l-1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). METHODS: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl-1/mIU∙l-1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. RESULTS: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. CONCLUSIONS: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl-1/mIU∙l-1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03224312).

Effects of a 12-week exercise-based intervention on weight management in overweight or obese breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivors face dual challenges: long-term sequelae of treatment and the risk of recurrent disease. Furthermore, obesity and a sedentary lifestyle can complicate both challenges. We aimed to assess the effect of a 12-week exercise-based weight-management program in overweight/obese breast cancer survivors. METHODS: A two-arm, single-blinded, randomized controlled trial was conducted among 60 overweight/obese, stage 0-III breast cancer survivors. During the 12-week program, the intervention group received weekly information support, fortnightly exercise prescriptions, including aerobic and resistance exercises to perform at home, and one dietary instruction. The control group received information support about weight management and exercise. Weight, body composition, and physical fitness data were collected at baseline, postintervention, and the 3-month follow-up. RESULTS: The intervention group showed significant improvements in body weight and all adiposity indices, including body mass index, waist circumference, and %body fat, in comparison with baseline (P < 0.001) and the control group (P < 0.05). Both groups showed no significant changes in fat-free mass during the 6-month period (P > 0.05). International Physical Activity Questionnaire scores and left grip strength increased significantly in the intervention group in comparison with the baseline (P < 0.01) and the control group (P < 0.05). Right grip strength, lower-body strength, and aerobic endurance showed no significant intergroup differences (P > 0.05). CONCLUSIONS: A combination of exercise prescription and weight-loss interventions yielded clinically meaningful weight loss in overweight/obese breast cancer survivors. These findings may facilitate the incorporation of home-based exercise and weight management into breast cancer treatment and survivorship care.

The Underexplored Mechanisms of Wheat Resistance to Leaf Rust.

Wheat leaf rust, caused by the obligate biotrophic fungus Puccinia triticina Eriks. (Pt), is one of the most common wheat foliar diseases that continuously threatens global wheat production. Currently, the approaches used to mitigate pathogen infestation include the application of fungicides and the deployment of resistance genes or cultivars. However, the continuous deployment of selected resistant varieties causes host selection pressures that drive Pt evolution and promote the incessant emergence of new virulent races, resulting in the demise of wheat-resistant cultivars after several years of planting. Intriguingly, diploid wheat accessions were found to confer haustorium formation-based resistance to leaf rust, which involves prehaustorial and posthaustorial resistance mechanisms. The prehaustorial resistance in the interaction between einkorn and wheat leaf rust is not influenced by specific races of the pathogen. The induced defense mechanism, known as systemic acquired resistance, also confers durable resistance against a wide array of pathogens. This review summarizes the host range, pathogenic profile, and evolutionary basis of Pt; the molecular basis underlying wheat-Pt interactions; the cloning and characterization of wheat leaf rust resistance genes; prehaustorial and posthaustorial resistance; systemic acquired resistance; and the role of reactive oxygen species. The interplay between climatic factors, genetic features, planting dates, and disease dynamics in imparting resistance is also discussed.

Distinct resting-state effective connectivity of large-scale networks in first-episode and recurrent major depression disorder: evidence from the REST-meta-MDD consortium.

Introduction: Previous studies have shown disrupted effective connectivity in the large-scale brain networks of individuals with major depressive disorder (MDD). However, it is unclear whether these changes differ between first-episode drug-naive MDD (FEDN-MDD) and recurrent MDD (R-MDD). Methods: This study utilized resting-state fMRI data from 17 sites in the Chinese REST-meta-MDD project, consisting of 839 patients with MDD and 788 normal controls (NCs). All data was preprocessed using a standardized protocol. Then, we performed a granger causality analysis to calculate the effectivity connectivity (EC) within and between brain networks for each participant, and compared the differences between the groups. Results: Our findings revealed that R-MDD exhibited increased EC in the fronto-parietal network (FPN) and decreased EC in the cerebellum network, while FEDN-MDD demonstrated increased EC from the sensorimotor network (SMN) to the FPN compared with the NCs. Importantly, the two MDD subgroups displayed significant differences in EC within the FPN and between the SMN and visual network. Moreover, the EC from the cingulo-opercular network to the SMN showed a significant negative correlation with the Hamilton Rating Scale for Depression (HAMD) score in the FEDN-MDD group. Conclusion: These findings suggest that first-episode and recurrent MDD have distinct effects on the effective connectivity in large-scale brain networks, which could be potential neural mechanisms underlying their different clinical manifestations.

The Role of Exosomes from Mesenchymal Stem Cells in Spinal Cord Injury: A Systematic Review.

Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.

Effectiveness of Nonpharmacologic Interventions for Chemotherapy-Induced Peripheral Neuropathy in Patients With Breast Cancer: A Systematic Review and Network Meta-analysis.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient. OBJECTIVE: To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC. METHODS: We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas). RESULTS: A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59). CONCLUSIONS: Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings. IMPLICATIONS FOR PRACTICE: This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.

Effectiveness of Nonpharmacologic Interventions for Chemotherapy-Related Cognitive Impairment in Breast Cancer Patients: A Systematic Review and Network Meta-analysis.

BACKGROUND: Neurotoxicity is a major adverse effect of chemotherapy in breast cancer (BC) patients. A number of nonpharmacologic interventions are used to alleviate chemotherapy-related cognitive impairment (CRCI), but no studies have compared their effectiveness. OBJECTIVES: The aim of this study was to identify and compare the effectiveness of different nonpharmacologic interventions for CRCI in BC patients. METHODS: A systematic review and network meta-analysis was conducted following the Cochrane guidelines. All randomized controlled trials were searched in the Cochrane Library, PubMed, MEDLINE (via OVID), Web of Science, EMBASE, and CINAHL databases from inception to September 2021. Studies using nonpharmacologic interventions to manage CRCI symptoms were included. A network meta-analysis and a comparative effects ranking were completed by STATA v14.0. RESULTS: Twelve studies with 8 nonpharmacologic interventions were included. For subjective outcomes on CRCI, there was no significant difference between nonpharmacologic interventions. For objective outcomes, qigong and exercise were more effective than the psychotherapy. Qigong and exercise were also more effective than music therapy. The top 3 interventions were psychotherapy (83.4%), music therapy (60.8%), and electroacupuncture (52.5%) for subjective outcomes and qigong (87.7%), exercise (82.1%), and electroacupuncture (70.3%) for objective outcomes. CONCLUSION: In the subjective evaluation, it was difficult to judge which interventions are best, but psychotherapy had the greatest probability. For objective evaluation, qigong and exercise may be the best nonpharmacologic interventions. IMPLICATIONS FOR PRACTICE: This study provides evidence for the effectiveness of nonpharmacologic interventions for CRCI in BC patients and facilitates support for future clinical trials and work.