N-of-1 medicine.

ABSTRACT: The fields of precision and personalised medicine have led to promising advances in tailoring treatment to individual patients. Examples include genome/molecular alteration-guided drug selection, single-patient gene therapy design and synergy-based drug combination development, and these approaches can yield substantially diverse recommendations. Therefore, it is important to define each domain and delineate their commonalities and differences in an effort to develop novel clinical trial designs, streamline workflow development, rethink regulatory considerations, create value in healthcare and economics assessments, and other factors. These and other segments are essential to recognise the diversity within these domains to accelerate their respective workflows towards practice-changing healthcare. To emphasise these points, this article elaborates on the concept of digital health and digital medicine-enabled N-of-1 medicine, which individualises combination regimen and dosing using a patient's own data. We will conclude with recommendations for consideration when developing novel workflows based on emerging digital-based platforms.

Involving patients in the process: Development of a constipation patient-reported outcome measure for symptoms and quality of life.

Objective: Patient-reported outcome measures (PROMs) are useful standardized tools to measure current patient health status and well-being. While there are existing constipation-related PROMs, the majority of PROMs were not developed with adequate patient involvement and few examined content validity. Accordingly, the current study aimed to develop a constipation PROM with multiple phases of patient and clinician involvement. Methods: To generate PROM items, 15 patients with chronic constipation (age range =28-79 years, 10 females) underwent a qualitative interview exploring their experiences with chronic constipation. Following that, eight clinical experts completed the content validity index (CVI) ratings of all the items generated to assess content validity. Based on results of the content validity assessment, relevant items were maintained and 12 participants with chronic constipation were re-interviewed to obtain feedback about comprehensibility, comprehensiveness and relevance. Results: Six themes and 25 sub-themes emerged from the qualitative interview, and an initial list of 33 symptom items and 18 quality of life (QoL) items were generated. Based on the CVIs calculated, 11 symptom items and nine QoL items were maintained with the scale-content validity index indicating excellent content validity. Overall, participants indicated the PROM to be relevant, comprehensive and easy to understand however, minor amendments were made to improve the three qualities of interest. Conclusion: The current study developed a constipation PROM that measures both symptom severity and constipation-related QoL, with supporting evidence for relevance, comprehensiveness and comprehensibility. Further prioritization should be given to validating and exploring new digital modalities of PROM administration.

Personalization and localization as key expectations of digital health intervention in women pre- to post-pregnancy.

Health behaviors before, during and after pregnancy can have lasting effects on maternal and infant health outcomes. Although digital health interventions (DHIs) have potential as a pertinent avenue to deliver mechanisms for a healthy behavior change, its success is reliant on addressing the user needs. Accordingly, the current study aimed to understand DHI needs and expectations of women before, during and after pregnancy to inform and optimize future DHI developments. Forty-four women (13 pre-, 16 during and 15 postpregnancy; age range = 21-40 years) completed a 60-minute, semistructured, qualitative interview exploring participant's experience in their current phase, experience with digital health tools, and their needs and expectations of DHIs. Interviews were audio-recorded, transcribed verbatim and thematically analyzed. From the interviews, two core concepts emerged-personalization and localization of DHI. Between both concepts, five themes and nine subthemes were identified. Themes and subthemes within personalization cover ideas of two-way interactivity, journey organization based on phases and circumstances, and privacy trade-off. Themes and subthemes within localization cover ideas of access to local health-related resources and information, and connecting to local communities through anecdotal stories. Here we report, through understanding user needs and expectations, the key elements for the development and optimization of a successful DHI for women before, during and after pregnancy. To potentially empower downstream DHI implementation and adoption, these insights can serve as a foundation in the initial innovation process for DHI developers and be further built upon through a continued co-design process.

Comparison of visual function before and after wearing amber filter in low vision patients with primary retinitis pigmentosa / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the visual function of low-vision patients with primary retinal pigmentosa(RP)before and after wearing amber filter.METHODS: Self-control before and after study. A total of 30 patients(60 eyes)with low vision who were diagnosed with primary RP in the ophthalmology clinic of Xi'an No.1 Hospital from August 2021 to March 2022 were collected. The uncorrected distance visual acuity(UCDVA), best-corrected distance visual acuity(BCDVA), uncorrected near visual acuity(UCNVA), best-corrected near visual acuity(BCNVA), visual field and Farnsworth-Munsell(FM)-100 color visions were recorded before and after wearing amber filter. The contrast sensitivity(CS)in three visual environments including bright room, darkroom and darkroom with glare was measured and recorded respectively, and the changes of those parameters were analyzed before and after wearing filter.RESULTS: UCDVA and BCDVA after wearing the filter were better than those before wearing(t=-2.32, P<0.001; t=-6.77, P<0.001), while there was no statistically significant difference in UCNVA and BCNVA before and after wearing filter. The visual field index(VFI)after wearing filter was lower than that before wearing(t=8.62, P<0.001), and the mean defect(MD)of visual field was greater than that before wearing(t=7.73, P<0.001). FM100 color chess test showed that both total error score(TES)and partial error score(PES)in multiple regions were higher than those before wearing filter(P<0.001). After wearing, the CS of each frequency band in the environment of bright room and darkroom with glare was higher than that before wearing(P<0.001), and there was no statistically significant difference in each frequency band before and after wearing amber filter under the environment of darkroom without glare.CONCLUSION: Patients with low vision of primary RP showed improved UCDVA and BCDVA, but unchanged UCNVA and BCNVA after wearing amber filter, while the visual field and color discrimination were worse than those before wearing filter. The CS of the bright room and darkroom with glare environment was improved than before wearing filter, while there were no significant changes in CS under darkroom without glare.

Effects of primary acquired nasolacrimal duct obstruction on tear film and ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of primary acquired nasolacrimal duct obstruction(PANDO)on the tear film and ocular surface using LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer.METHODS: A self-controlled clinical trials. A total of 40 patients diagnosed with unilateral PANDO for at least 6mo who were admitted to our department from September 2021 to March 2022 were enrolled in the study, and the healthy eyes of the patients were assessed as control group. The LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer were used to measure the changes in related parameters of the tear film and ocular surface in both eyes.RESULTS: The non-invasive tear meniscus height(NITMH), stimulated NITMH, loss rate of upper meibomian gland, nasal and temporal ciliary redness index, temporal conjunctival redness index of the affected eyes were higher than healthy eyes(P<0.05), but there were no statistical differences in the non-invasive break-up time(NIBUT), loss rate of lower meibomian gland, nasal conjunctival redness index, dry eye grading, blink responses, partial blink rate and lipid layer thickness(LLT)between the both eyes(P>0.05).CONCLUSION: PANDO may lead to the aggravation of ocular surface inflammation and the loss of upper meibomian gland, and damage the ocular surface of patients. Attention should be paid to the early treatment of PANDO.

Progress and prospect of biological treatment for rotator cuff injury repair / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress in biotherapy of rotator cuff injury in recent years, in order to provide help for clinical decision-making of rotator cuff injury treatment.@*METHODS@#The literature related to biotherapy of rotator cuff injury at home and abroad in recent years was widely reviewed, and the mechanism and efficacy of biotherapy for rotator cuff injury were summarized from the aspects of platelet-rich plasma (PRP), growth factors, stem cells, and exosomes.@*RESULTS@#In order to relieve patients' pain, improve upper limb function, and improve quality of life, the treatment of rotator cuff injury experienced an important change from conservative treatment to open surgery to arthroscopic rotator cuff repair. Arthroscopic rotator cuff repair plus a variety of biotherapy methods have become the mainstream of clinical treatment. All kinds of biotherapy methods have ideal mid- and long-term effectiveness in the repair of rotator cuff injury. The biotherapy method to promote the healing of rotator cuff injury is controversial and needs to be further studied.@*CONCLUSION@#All kinds of biotherapy methods show a good effect on the repair of rotator cuff injury. It will be an important research direction to further develop new biotherapy technology and verify its effectiveness.

Preparation and Characterization of Extracellular Matrix Hydrogels Derived from Acellular Cartilage Tissue.

Decellularized matrices can effectively reduce severe immune rejection with their cells and eliminated nucleic acid material and provide specific environments for tissue repair or tissue regeneration. In this study, we prepared acellular cartilage matrix (ACM) powder through the decellularization method and developed ACM hydrogels by physical, chemical, and enzymatic digestion methods. The results demonstrated that the small size group of ACM hydrogels exhibited better gel conditions when the concentration of ACM hydrogels was 30 and 20 mg/mL in 1N HCl through parameter adjustment. The data also confirmed that the ACM hydrogels retained the main components of cartilage: 61.18% of glycosaminoglycan (GAG) and 78.29% of collagen, with 99.61% of its DNA removed compared to samples without the decellularization procedure (set as 100%). Through turbidimetric gelation kinetics, hydrogel rheological property analysis, and hydrogel tissue physical property testing, this study also revealed that increasing hydrogel concentration is helpful for gelation. Besides, the ex vivo test confirmed that a higher concentration of ACM hydrogels had good adhesive properties and could fill in cartilage defects adequately. This study offers useful information for developing and manufacturing ACM hydrogels to serve as potential alternative scaffolds for future cartilage defect treatment.

Tubule-mitophagic secretion of SerpinG1 reprograms macrophages to instruct anti-septic acute kidney injury efficacy of high-dose ascorbate mediated by NRF2 transactivation.

High-dose ascorbate confers tubular mitophagy responsible for septic acute kidney injury (AKI) amelioration, yet its biological roles in immune regulation remain poorly understood. Methods: The role of tubular mitophagy in macrophage polarization upon high-dose ascorbate treatment was assessed by fluorescence-activated cell sorter analysis (FACS) in vitro and by immunofluorescence in AKI models of LPS-induced endotoxemia (LIE) from Pax8-cre; Atg7 flox/flox mice. The underlying mechanisms were revealed by RNA-sequencing, gene set enrichment analysis (GSEA), luciferase reporter, chromatin immunoprecipitation (ChIP) and adeno-associated viral vector serotype 9 (AAV9) delivery assays. Results: High-dose ascorbate enables conversion of macrophages from a pro-inflammatory M1 subtype to an anti-inflammatory M2 subtype in murine AKI models of LIE, leading to decreased renal IL-1ß and IL-18 production, reduced mortality and alleviated tubulotoxicity. Blockade of tubular mitophagy abrogates anti-inflammatory macrophages polarization under the high-dose ascorbate-exposed coculture systems. Similar abrogations are verified in LIE mice with tubular epithelium-specific ablation of Atg7, where the high-dose ascorbate-inducible renal protection and survival improvement are substantially weaker than their control littermates. Mechanistically, high-dose ascorbate stimulates tubular secretion of serpin family G member 1 (SerpinG1) through maintenance of mitophagy, for which nuclear factor-erythroid 2 related factor 2 (NRF2) transactivation is required. SerpinG1 perpetuates anti-inflammatory macrophages to prevent septic AKI, while kidney-specific disruption of SerpinG1 by adeno-associated viral vector serotype 9 (AAV9)-short hairpin RNA (shRNA) delivery thwarts the anti-inflammatory macrophages polarization and anti-septic AKI efficacy of high-dose ascorbate. Conclusion: Our study identifies SerpinG1 as an intermediate of tubular mitophagy-orchestrated myeloid function during septic AKI and reveals a novel rationale for ascorbate-based therapy.

Understanding the user: Patients' perception, needs, and concerns of health apps for chronic constipation.

Objective: Chronic constipation is a prevalent gastrointestinal disorder that requires long-term management and treatment adherence. With increasing smartphone usage, health app adoption represents an opportunity to incorporate personalized, patient-led care into chronic constipation management. Despite the number of apps available targeting patients with constipation, studies have not yet examined user needs and barriers towards successful app adoption and sustained usage. Accordingly, the current study explored user perception, needs, and concerns of health apps in patients with chronic constipation. Methods: Fifteen participants with chronic constipation (age range = 28-79 years, 10 females) in Singapore completed a 60 min semi-structured qualitative interview exploring participant's experiences with and attitudes towards chronic constipation and health apps. Participants also completed two questionnaires regarding their constipation symptoms and general technology usage. Interviews were audio-recorded, transcribed verbatim, and coded using NVivo. Results: Four themes and 10 sub-themes were identified using inductive thematic analysis. Themes and sub-themes cover importance of patient identity, disease-based expectations of health apps, barriers towards adoption and sustained usage of health apps, necessary conditions when adopting health apps (including perception of supportive benefits, clear understanding of app intention, personalized technology, and trusted sources), and push factor expectations which includes creative engagement and incentivization embedded within the app. Conclusion: The findings captured barriers and key elements necessary for successful health app adoption and continued usage by patients with chronic constipation. Identified elements that matter to patients can provide app developers with user-focused insights and recommendations to develop effective health apps that sustain user engagement.

A Systematic Review of the Development and Psychometric Properties of Constipation-Related Patient-Reported Outcome Measures: Opportunities for Digital Health.

Background/Aims: Constipation can be a chronic condition that impacts daily functioning and quality of life (QoL). To aid healthcare providers in accurately assessing patient symptoms and treatment outcomes, patient-related outcome measures (PROMs) have been increasingly adopted in clinical settings. This review aims to (1) evaluate the methodological quality and measurement properties of constipation-related PROMs, using the COnsensus-based Standards for the selection of health Measurement INtruments (COSMIN) criteria; and (2) assess the modes of digital dissemination of constipation-related PROMs. Methods: PubMed, Embase, and PsycINFO databases were searched and 11 011 records ranging from 1989 to 2020 were screened by 2 independent reviewers. A total of 26 studies (23 PROMs; 18 measuring symptom-related items and 5 measuring constipation-related QoL items) were identified for the review and assessed. Results: There were multiple variations between PROMs, including subtypes of constipation, methods of administration, length of PROM and recall period. While no PROM met all the COSMIN quality standards for development and measurement properties, 5 constipation-related PROMs received at least 4 (out of 7) sufficient ratings. Only 2 PROMs were developed in Asia. Five PROMs were administered through digital methods during the validation process but methods of adapting the PROMs into digital formats were not reported. Conclusions: The constipation-related PROMs identified in this review present varying quality of development and validation, with an overall need for improvement. Further considerations should be given towards more consistent methodology and reporting of PROM development, increase in culturally-specific PROMs, and better reporting of protocol for the digitisation of PROMs.

ECG Classification Based on Wasserstein Scalar Curvature.

Electrocardiograms (ECG) analysis is one of the most important ways to diagnose heart disease. This paper proposes an efficient ECG classification method based on Wasserstein scalar curvature to comprehend the connection between heart disease and the mathematical characteristics of ECG. The newly proposed method converts an ECG into a point cloud on the family of Gaussian distribution, where the pathological characteristics of ECG will be extracted by the Wasserstein geometric structure of the statistical manifold. Technically, this paper defines the histogram dispersion of Wasserstein scalar curvature, which can accurately describe the divergence between different heart diseases. By combining medical experience with mathematical ideas from geometry and data science, this paper provides a feasible algorithm for the new method, and the theoretical analysis of the algorithm is carried out. Digital experiments on the classical database with large samples show the new algorithm's accuracy and efficiency when dealing with the classification of heart disease.

Analyze on the value of conjunctival impression cytology in the diagnosis of allergic conjunctivitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the value of conjunctival impression cytology(CIC)in the diagnosis of allergic conjunctivitis(AC). <p>METHODS: A case-control study. Forty patients(80 eyes)who were clinically diagnosed with AC in our department from January to February 2021 were included in the study,and 40 normal controls(80 eyes)were enrolled too. All subjects underwent double upper palpebral CIC examinations. Observed the morphology and number of conjunctival eosinophils and carried out Tseng classification in each group. To Compare the differences between the results of the two groups and analyze the effects of gender, age and course of disease on the results of CIC eosinophil examination in AC group.<p>RESULTS: The positive rate of eosinophils in the upper palpebral CIC examination of AC patients was significantly higher than that of the normal control group(χ²=57.744, <i>P</i><0.001); The Tseng grade of AC patients was also higher than that of the normal control group(<i>Z</i>=-2.453, <i>P</i><0.05). Gender, age and course of disease had no significant effect on the results of CIC eosinophils in AC group(all <i>P</i> >0.05).<p>CONCLUSION: CIC examination is simple, and the result is objective and accurate. It has good application value in the diagnosis of AC.

A Systematic Review of the Development and Psychometric Properties of Constipation-related Patient-reported Outcome Measures: Opportunities for Digital Health

Background/Aims@#Constipation can be a chronic condition that impacts daily functioning and quality of life (QoL). To aid healthcare providers in accurately assessing patient symptoms and treatment outcomes, patient-related outcome measures (PROMs) have been increasingly adopted in clinical settings. This review aims to (1) evaluate the methodological quality and measurement properties of constipationrelated PROMs, using the COnsensus-based Standards for the selection of health Measurement INtruments (COSMIN) criteria; and (2) assess the modes of digital dissemination of constipation-related PROMs. @*Methods@#PubMed, Embase, and PsycINFO databases were searched and 11 011 records ranging from 1989 to 2020 were screened by 2 independent reviewers. A total of 26 studies (23 PROMs; 18 measuring symptom-related items and 5 measuring constipation-related QoL items) were identified for the review and assessed. @*Results@#There were multiple variations between PROMs, including subtypes of constipation, methods of administration, length of PROM and recall period. While no PROM met all the COSMIN quality standards for development and measurement properties, 5 constipationrelated PROMs received at least 4 (out of 7) sufficient ratings. Only 2 PROMs were developed in Asia. Five PROMs were administered through digital methods during the validation process but methods of adapting the PROMs into digital formats were not reported. @*Conclusions@#The constipation-related PROMs identified in this review present varying quality of development and validation, with an overall need for improvement. Further considerations should be given towards more consistent methodology and reporting of PROM development, increase in culturally-specific PROMs, and better reporting of protocol for the digitization of PROMs.

Interruption of neutrophil extracellular traps formation dictates host defense and tubular HOXA5 stability to augment efficacy of anti-Fn14 therapy against septic AKI.

The immunosuppressive, inflammatory microenvironment orchestrated by neutrophil extracellular traps (NETs) plays a principal role in pathogenesis of sepsis. Fibroblast growth factor-inducible molecule 14 (Fn14) has been established as a potential target for septic acute kidney injury (AKI), making further therapeutic benefits from combined NETs and Fn14 blockade possible. Methods: The concurrence of NETs and Fn14 in mice and patients with septic AKI were assessed by immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and in silico studies. Survival, histopathological and biochemical analyses of wild-type and PAD4-deficient CMV-Cre; PAD4 fl/fl mice with septic AKI were applied to evaluate the efficacy of either pharmacological or genetic NETs interruption in combination with Fn14 blockade. Molecular mechanisms underlying such effects were determined by CRISPR technology, fluorescence-activated cell sorter analysis (FACS), cycloheximide (CHX) pulse-chase, luciferase reporter and chromatin immunoprecipitation (ChIP) assay. Results: NETs formation is concurred with Fn14 upregulation in murine AKI models of abdominal, endotoxemic, multidrug-resistant sepsis as well as in serum samples of patients with septic AKI. Pharmacological or genetic interruption of NETs formation synergizes with ITEM-2, a monoclonal antibody (mAb) of Fn14, to prolong mice survival and provide renal protection against abdominal sepsis, the effects that could be abrogated by elimination of macrophages. Interrupting NETs formation predominantly perpetuates infiltration and survival of efferocytic growth arrest-specific protein 6+ (GAS6+) macrophages in combination with ITEM-2 therapy and enhances transcription of tubular cell-intrinsic Fn14 in a DNA methyltransferase 3a (DNMT3a)-independent manner through dismantling the proteasomes-mediated turnover of homeobox protein Hox-A5 (HOXA5) upon abdominal sepsis challenge or LPS stimuli. Pharmacological NETs interruption potentiates the anti-septic AKI efficacy of ITEM-2 in murine models of endotoxemic and multidrug-resistant sepsis. Conclusion: Our preclinical data propose that interrupting NETs formation in combination with Fn14 mAb might be a feasible therapeutic strategy for septic AKI.

Prognostic Immune-Related Analysis Based on Differentially Expressed Genes in Left- and Right-Sided Colon Adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) can be divided into left-sided and right-sided COAD (LCCs and RCCs, respectively). They have unique characteristics in various biological aspects, particularly immune invasion and prognosis. The purpose of our study was to develop a prognostic risk scoring model (PRSM) based on differentially expressed immune-related genes (IRGs) between LCCs and RCCs, therefore the prognostic key IRGs could be identified. METHODS: The gene sets and clinical information of COAD patients were derived from TCGA and GEO databases. The comparison of differentially expressed genes (DEGs) of LCCs and RCCs were conducted with appliance of "Limma" analysis. The establishment about co-expression modules of DEGs related with immune score was conducted by weighted gene co-expression network analysis (WGCNA). Furthermore, we screened the module genes and completed construction of gene pairs. The analysis of the prognosis and the establishment of PRSM were performed with univariate- and lasso-Cox regression. We employed the PRSM in the model group and verification group for the purpose of risk group assignment and PRSM accuracy verification. Finally, the identification of the prognostic key IRGs was guaranteed by the adoption of functional enrichment, "DisNor" and protein-protein interaction (PPI). RESULTS: A total of 215 genes were screened out by differential expression analysis and WGCNA. A PRSM with 16 immune-related gene pairs (IRGPs) was established upon the genes pairing. Furthermore, we confirmed that the risk score was an independent factor for survival by univariate- and multivariate-Cox regression. The prognosis of high-risk group in model group (P < 0.001) and validation group (P = 0.014) was significantly worse than that in low-risk group. Treg cells (P < 0.001) and macrophage M0 (P = 0.015) were highly expressed in the high-risk group. The functional analysis indicated that there was significant up-regulation with regard of lymphocyte and cytokine related terms in low-risk group. Finally, we identified five prognostic key IRGs associated with better prognosis through PPI and prognostic analysis, including IL2RB, TRIM22, CIITA, CXCL13, and CXCR6. CONCLUSION: Through the analysis and screening of the DEGs between LCCs and RCCs, we constructed a PRSM which could predicate prognosis of LCCs and RCCs, and five prognostic key IRGs were identified as well. Therefore, the basis for identifying the benefits of immunotherapy and immunomodulatory was built.

LncRNA EGOT regulates the proliferation and apoptosis of colorectal cancer by miR-33b-5p/CROT axis.

Accumulating researches have proved that long noncoding RNAs (lncRNAs) regulate a variety of cellular processes during cancer progression. However, the detailed function of most lncRNAs in colorectal cancer (CRC) remains mostly unknown. This study was aimed at exploring the specific role of lncRNA EGOT in CRC. Data from this study revealed that EGOT expression was obviously upregulated in CRC tissues and cell lines, and high EGOT expression indicated poor overall survival of CRC patients. Besides, functional assays proved that EGOT knockdown inhibited cell proliferation and promoted cell apoptosis in CRC. Then, subsequent molecular mechanism assays uncovered that EGOT could bind with miR-33b-5p and negatively regulate miR-33b-5p expression. Additionally, CROT was a downstream target of miR-33b-5p. Further, rescued-function assays suggested that the suppressive influence of EGOT depletion on CRC progression was reversed by miR-33b-5p inhibition or CROT overexpression. In conclusion, lncRNA EGOT mediates the tumor-facilitating part in CRC via miR-33b-5p/CROT pathway.

Prognostic Value of Prolonged Feeding Intolerance in Predicting All-Cause Mortality in Critically Ill Patients: A Multicenter, Prospective, Observational Study.

BACKGROUND: The 2012 European Society of Intensive Care Medicine (ESICM) guidelines provided a clear definition of feeding intolerance (FI). The study aimed to investigate the association between FI based on the current ESICM definition and clinical outcome and to further explore the effect of the duration of FI on mortality. METHODS: Adult patients from 14 general intensive care units (ICUs) with an expected ICU stay ≥24 hours were prospectively studied. Based on FI duration in the first week of admission to the ICU, FI was categorized as 7-day persistent feeding tolerance (FT), delayed FT, delayed FI, and 7-day persistent FI. The primary outcomes were 28-day and 60-day all-cause mortality. RESULTS: Of 499 patients, the prevalence of 3-day and 7-day persistent FI was 39.2% (n = 196) and 25.4% (n = 106), respectively. The patients with 3-day FT had lower risk of 28-day and 60-day mortality rates and higher prevalence in ventilator weaning and vasoactive medication on the seventh day of ICU admission than those with 3-day FI. Three-day FI remained an independent predictor for 60-day mortality. In a subgroup analysis including 418 patients with 7-day survival, compared with those with 7-day persistent FT, the odds ratios of 60-day mortality were 1.67, 1.97, and 2.62 in the patients with delayed FT, delayed FI, and 7-day persistent FI, respectively. CONCLUSION: FI was associated with increased mortality and longer duration of mechanical ventilation and vasoactive support. Prolonged or relapsing FI represented an incremental risk of adverse outcomes in critically ill patients.

[Effects of Converting Farmland into Forest and Grassland on Soil Nitrogen Component and Conversion Enzyme Activity in the Mountainous Area of Southern Ningxia].

The effects of the policy of converting farmland to forest and grassland on soil nitrogen content and conversion enzyme activity were studied. Caragana intermedia, Prunus davidiana, Medicago spp., and Stipa bungeana and a corn control were examined to determine the concentrations of seven soil nitrogen components and the activity of two nitrogen conversion enzymes. The main factors affecting soil nitrogen distributions and transformation was also explored using redundancy analysis (RDA). The results showed that:① Compared with the corn soil, the content of particulate organic nitrogen, light fraction organic nitrogen, microbial biomass nitrogen, and ammonium nitrogen in the Stipa bungeana soil increased by 35.3%, 83.3%, 64.2%, and 110.0%, respectively; soluble organic nitrogen and ammonium in the Medicago spp. soil increased by 0.7% and 67.5%, respectively; the asparaginase and protease activities in the Stipa bungeana soil increased by 360% and 144.8%, respectively, indicating that conversion of farmland to forest and grassland has a promoting effect on nitrogen components and conversion enzyme activity; ②The content of organic nitrogen, light organic nitrogen, particulate organic nitrogen, and soluble organic nitrogen in the Prunus davidiana soil was 3.7%, 133.3%, 70.6%, and 28.1% higher than that of the corn soil, respectively. The light fraction organic nitrogen content of the Caragana intermedia soil and microbial biomass nitrogen content of the Prunus davidiana soil was 16.7% and 49.6% higher than that of the corn soil, respectively. Protease activity in the Caragana intermedia and Prunus davidiana soils was higher than in the corn soil, further indicating that the conversion of farmland to forest and grassland promotes the accumulation of nitrogen components and enhances conversion enzyme activity; ③ The RDA and environmental factor explanation rate results indicated that soil water content, pH, and soil organic carbon were the key factors affecting nitrogen distribution and transformation in the mountainous area of southern Ningxia. Overall, the results show that converting farmland into forest and grassland has changed conversion enzyme activity and has promoted the accumulation of nitrogen components in soils. This provides a theoretical basis for ecological restoration and soil quality management in the Loess Plateau.