The revised definition of acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) was proposed in 2016, but changes in the incidence and impact on prognosis of the re-defined AE compared to those of the previous definition remain unclear. Clinical data of 445 patients with IPF (biopsy proven cases: 165) were retrospectively reviewed. The median follow-up period was 36.8 months and 17.5% (n = 78) experienced AE more than once. The 1- and 3-year incidence rates of AE were 6.7% and 16.6%, respectively, and idiopathic AE accounted for 82.1% of AE. Older age, lower diffusing capacity of the lung for carbon monoxide and 10% relative decline in forced vital capacity for 6 months were independently associated with AE. The in-hospital mortality rate following AE was 29.5%. In the multivariable analysis, AE was independently associated with poor prognosis in patients with IPF. Compared to the old definition, the revised definition relatively increased the incidence of AE by 20.4% and decreased the in-hospital mortality by 10.1%. Our results suggest that the revised definition affects approximately 20% increase in the incidences and 10% reduction in the in-hospital mortality of AE defined by the past definition. The natural course of IPF is variable and unpredictable; some patients have a relatively steady decline in lung function, punctuated by acute respiratory worsening, named acute exacerbation (AE)4. The incidence of AE ranged from 9.6 to 61% and AE was associated with a high mortality rate varying between 12 to 100%10.Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease of unknown etiology, with median survival of 3 years11. Based on the revised definition, a recent study reported that AE of IPF accounted for 30% of acute respiratory deterioration that required hospitalization (n = 106) and was significantly associated with 90-day mortality 12. Most reports of AE have been investigated based on the old definition. However, compared to the old definition, the effect of the new definition on the incidence and outcome of AE has not been reported. As this is important for designing future clinical trials, our study aimed to investigate the incidence, risk factors, and outcomes of AE-IPF by the revised definition and compare them with those of the old definition.In 2016, the revised diagnostic criteria of AE-IPF was proposed, which included any acute respiratory events characterized by acute or subacute worsening or development of dyspnea, typically within 1 month along with bilateral infiltration except for cardiogenic or volume overload pulmonary edema13. Among these, 69 patients who first presented with respiratory deterioration (RD) (n = 57), those treated for lung cancer (n = 11) or underwent lung transplantation (n = 1) were excluded. The remaining 445 patients with IPF (biopsy proven cases: 165) were finally included in this study /European Respiratory Society (ERS)/Japanese Respiratory Society/Latin American Thoracic Association consensus statementudy Fig. . The stu16, and the results were expressed as percentages of the normal predicted values. The 6-min walk test (6MWT) was performed according to the ERS/ATS guidelines17. Bronchoalveolar lavage (BAL) was performed based on ATS guideline18.Clinical and survival data were retrospectively collected from electronic medical records, telephone interviews, and/or records of National Health Insurance of Korea. Forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLco) and total lung capacity (TLC) were measured according to the ATS/ERS recommendation19. AE was defined based on the revised criteria put forth by Collard et al. in 201611 and further categorized as idiopathic or triggered AE, depending on whether underlying triggers could be identified. Patients who did not experience RD during follow-up were classified as the no-RD group, and those who experienced RD other than AE were categorized as the no-AE RD group. The suspected AE was defined as acute respiratory worsening in which all AE criteria could not meet due to missing data.Acute respiratory deterioration (RD) was defined as an acute worsening of dyspnea requiring hospitalization with newly developed radiologic abnormalitiesPneumocystis jiroveci in BAL fluid; serologic tests for cytomegalovirus and species of Mycoplasma, Legionella and Aspergillus; and urinary antigen tests for Streptococcuspneumoniae and Legionella.For microbiologic evaluation, we performed multiple microbiologic tests. Although BAL or endotracheal aspiration could not be performed in all patients with RD due to instability, at least sputum samples as one of respiratory samples were collected and tested in all patients. In addition to respiratory samples, blood and urine samples were tested for microbioloigic evaluation. Microbiological evaluation include viral antigen test using FITC-conjugated anti-virus polyclonal antibody for virus  or respiratory virus multiplex RT-PCR for virus  and direct fluorescence monoclonal antibody staining for 3. The relative changes in forced vital capacity (FVC) ≥ 10% from baseline for 6 months was defined as the disease progression (DP). The relative changes in FVC for 6 months from baseline were calculated as follows; (FVC % predicted after 6 months − FVC % predicted baseline)/FVC % predicted baseline × 100%20.The past definition of AE was based on the diagnostic criteria proposed in 2007t test or the Mann–Whitney U test was used for continuous variables, and the Chi-squared test or Fisher’s exact test was used to compare categorical variables. We analyzed risk factors and mortality rates based on the first AE. Cox proportional hazards analysis was employed to identify predicting variables for AE or the overall mortality. Logistic regression analysis was undertaken to determine predicting factors of in-hospital mortality in patients with AE. Variables with P value < 0.1 in the unadjusted analysis were entered into the multivariable models with backward, stepwise elimination method. Survival analysis was conducted using the Kaplan–Meier method, and differences were assessed by the long-rank test. All P values were two-tailed, and those < 0.05 were considered statistically significant. Data analysis was performed using the Statistical Package for the Social Sciences software version 25.0 .All values were expressed as mean ± standard deviation for continuous variables or percentages for categorical variables. The Student’s The patients’ mean age was 66.4 years, and 76.5% were male. The median follow-up period was 36.8 months (interquartile range 21.8–57.6 months). During follow-up, 119 (26.7%) patients experienced RD more than once (range 1–4 episodes), and 78 (65.5% of those with RD) experienced definite AE (range 1–3 episodes) Table . The 1-,2; resting and the lowest) during the 6MWT and more frequent DP than the no-RD group (Table 2 (resting and the lowest) during the 6MWT, and more frequent DP than those in the no-RD group.Patients in the RD group had higher CRP levels, lower lung function , shorter distance and lower oxygen saturation (SpOup Table . In the 2 (resting and the lowest) during the 6MWT, and DP were significantly associated with occurrence of AE in patients with IPF  than those with no-AE RD (n = 41). The in-hospital mortality between idiopathic and triggered AE groups did not differ . Among the patients with AE, the non-survivors, at the time of hospitalization, had shorter duration of dyspnea before hospitalization, more frequent fever, higher CRP levels, and lower arterial oxygen partial pressure/fractional inspired oxygen (P/F) ratio than the survivors  showed a higher in-hospital mortality rate  patients with IPF died. There were significant differences in overall survival from the diagnosis of IPF between patients experienced AE  and others  during the 6MWT, DP, and AE were significantly associated with poor prognosis in patients with IPF (Table p = 0.002), along with older age, lower BMI and FVC, DP, shorter distance and lower the minimum SpO2 during 6MWT.In the unadjusted Cox regression analysis, older age, lower body mass index (BMI), Charlson comorbidity index, FVC and DLco, shorter distance, and lower SpOPF Table . Followip = 0.003)  patients with IPF, and the 1-, 2- and 3-year cumulative incidences of AE were 4.2%, 8.9%, and 12%, respectively. The in-hospital mortality rates of patients with AE were 32.8%. While a lower P/F ratio was seen as an independent prognostic factor for in-hospital mortality in patients with AE Table , AE was 3) Table .p = 0.211) compared with those with idiopathic AE. However, overall mortality after hospitalization was similar between patients who experienced AE by both the definitions  in patients with IPF Fig. ; 14 patiIn this study using the revised definition of AE, the 1-, 2-, and 3-year incidences of AE were 6.7%, 12.6%, and 16.6%, respectively. Older age, lower DLco and DP (10% relative decline in FVC for 6 months) were predictors for AE. AE was associated with a poor prognosis and appeared to have a significant impact on overall survival in patients with IPF. The revised criteria increased incidence of AE by 20.4% compared to those by the previous definition, and decreased the in-hospital mortality by 10.1%.22 have reported incidence of AE based on the revised definition of AE. A study that included 225 patients with IPF, reported that the 1-year incidence of AE was 7.6%12. Okuda et al., in 107 patients with biopsy-proven IPF, also documented that cumulative incidence of AE was 9.6% for 1 year, 16.8% for 2 year and 23.9% for 3 years21. Moreover, Suzuki et al., using fibrotic ILD cohort (n = 1019), showed that AE occurred in 24% of patients with IPF (n = 462) during follow-up (median period: 3.4 years)22. Though these results were in line with our findings, they did not compare the results obtained using the new criteria with those of the older one.Several studies23. The results of our study are consistent with this finding. However, in our cohort, older age was one of risk factors for AE-IPF, which was not shown in previous studies22. The revised definition includes AE triggered by infection. The elderly are more susceptible to respiratory infections due to age-related dysfunction of the immune system (decrease in innate and adaptive immunity), and blunting of cough reflex or decline in mucociliary clearance24. These suggest that older age can be considered as a plausible risk factor of AE in our study. These results suggest that early diagnosis of IPF and early use of antifibrotic agents, and influenza or pneumococcal vaccination might be a useful prevention strategy of AE in patients with IPF25. Blood biomarkers  were also suggested to be useful in predicting prognosis in patients with AE-IPF26.In our study, older age, lower DLco and DP were independent predictors for AE-IPF. As documented in previous reports, lower lung function is the well-known risk factor for AE22. Okuda et al., showed that 90-day survival rate of the AE group (n = 39) was 50.4%, significantly lower than that of the non-AE group (P < 0.001)21. Suzuki et al., also, reported that AE was an independent predictor for mortality 22.The results of our study indicate that AE was an independent prognostic factor for overall mortality in patients with IPF. Some studies using the revised definition of AE also demonstrated that AE was the independent prognostic factors in patients with IPF27, several studies, using the revised definition of AE, also reported findings similar to our results28. Teramachi et al., in 35 IPF patients with AE, reported that there was no significant difference in 90-day mortality with respect to survival  between idiopathic (n = 24) and triggered AE (n = 11)12. Okuda et al., in 39 IPF patients with AE, also showed that there were no significant differences in 90-day survival rates  between idiopathic (n = 29) and triggered AE (n = 10)21. Moreover, Yamazoe et al., in 64 patients with AE-IPF, reported that there was no difference in terms of in-hospital mortality  between idiopathic (n = 42) and triggered AE (n = 22)28. However, Kato et al. reported that, in their 79 patients with AE-idiopathic interstitial pneumonia , patients with infection-triggered exacerbations  had significantly longer median survival duration than that in those with idiopathic or non-infection-triggered AEIIPs 29. 90-day mortality rate was significantly lower in patients with infection-triggered AE than in patients with idiopathic or non-infection-triggered AE IIPs . A possible cause of reduced in-hospital morality of triggered AE might be that triggered events are relatively easier to correct than idiopathic cases.In our study, there was no difference of in-hospital mortality between idiopathic and triggered AE, which supports the validity of the revised definition of AE. Except for one study conducted by Kishaba et al.3, the revised definition emphasizes the pathophysiology rather than the cause of acute deterioration; any acute deterioration showing the pathophysiology of acute lung injury was defined as an AE. Therefore, the revised definition do not require invasive diagnostic procedures to diagnose AE, and has changed our clinical practice in terms of avoiding invasive procedure to diagnose AE in patients with AE-IPF23. This change seems to be practical for both clinical practice as well as clinical trials. In our study, the revised criteria relatively increased incidence of AE by 20.4% compared to that by the previous one. In addition, mortality rate decreased by 10%, which reflects real clinical situation in terms of clinical outcomes in IPF patients with AE. Our cohort also showed that all suspected AE by the past definition was included as definite AE in the revised definition. This finding suggests that more patients with IPF may be eligible for future clinical trials involving AE-IPF.In contrast to the 2007 diagnostic criteria on AE-IPF28. Second, BAL or endotracheal aspiration was not performed in all patients with RD due to instability, but microbial tests, including respiratory virus PCR panels, were performed for all patients. Third, patients were diagnosed before the era of antifibrotic therapy, when anti-inflammatory agent such as corticosteroid was a standardized therapy. Because treatment with anti-fibrotic agents reduces AE in patients with IPF, we intended to use the clinical data of patients with IPF before the era of antifibrotic therapy to exclude the antifibrotic effect. This enabled comparison of our data with the previous results. Despite these limitations, our study could demonstrate clinical validity of the revised definition of AE in patients with IPF.This study has some limitations. First, it was a retrospective observational study performed at a single center, which may have limited the generalizability of the results. However, baseline characteristics of our patients were similar to those included in previous reportsIn conclusion, per the revised definition, approximately a fifth of patients with IPF experienced AE which exerted a significant impact on the prognosis. Our results suggest that the revised definition reflects 20.4% increase of incidence and 10% reduction of the in-hospital mortality in AE defined by the past definition, by reducing suspected cases of AE and including triggered cases. These results must be considered when interpreting past results and planning future clinical trials.Supplementary Information.


Dexamethasone is commonly used for antiemesis in surgical patients. It has been confirmed that long-term steroid use increases blood glucose level in both diabetic and non-diabetic patients, it is unclear how a single dose of intravenous dexamethasone used pre/intraoperatively for postoperative nausea and vomiting (PONV) prophylaxis would influence the blood glucose and wound healing in diabetic patients.The Pubmed, Cochrane Library, Embase, Web of Science databases, CNKI and Google Scholar were searched. The articles reporting a single dose dexamethasone administered intravenously for antiemesis in surgical patients with diabetes mellitus (DM) were included.I2 = 55.7%, P = 0.004), at the end of surgery , on postoperative day (POD) 1 , on POD 2 , and increased peak glucose level within 24 hours of surgery  compared with control. It indicated that dexamethasone caused the increase of perioperative glucose level at different time points by 0.439 to 1.087 mmol/L (7.902 to 19.566 mg/dL), and the increase of peak glucose level within 24 hours of surgery by 2.014 mmol/L (36.252 mg/dL) compared with control. Dexmethasone had no impact on wound infection  and healing (P < 0.05).Nine randomized controlled trials (RCTs) and 7 cohort studies were included in our meta-analysis. The results showed that dexamethasone increased glucose level intraoperatively  of peak glucose level within 24 hours of surgery in surgery patients with DM, the increase of glucose level at each time point perioperatively was even lower, and had no effect on wound healing. Thus, dexamethasone with a single dose could be safely used for PONV prophylaxis in diabetic patients.The protocol of this systematic review was registered in INPLASY with the registration number INPLASY202270002.The online version contains supplementary material available at 10.1186/s13741-023-00293-4. Dexamethasone is commonly used and very effective to prevent postoperative nausea and vomiting (PONV), and dexamethasone combined with 5-HT3 receptor antagonist is recommended as the first-line antiemetic for children  and MOOSE  guidelines. The protocol of this systematic review was registered in INPLASY with the registration number INPLASY202270002.The inclusion criteria included: (a) studies comparing dexamethasone perioperatively with control  in adult patients with diabetes mellitus undergoing non-cardiac surgery; (b) dexamethasone with a single dose administered intravenously for antiemesis; (c) data about the relationship between dexamethasone and glucose responses with or without wound healing and infection. The exclusion criteria included: (a) studies comparing different doses of dexamethasone without control; (b) dexamethasone administered only postoperatively; (c) dexamethasone with two or more doses for antiemesis; (d) dexamethasone with large dosage for other purposes (not for antiemesis); (e) conference, review or case report.Two researchers independently (Y. J. and J.W.) searched the databases of Pubmed, Embase, Cochrane Library, Web of science, CNKI, and Google Scholar from 1990 to June 2022, and screened the articles. The key words and medical subject headings (MeSH) included dexamethasone, steroids, surgery, surgical, operation, operative, diabetes mellitus, diabetic, diabetes, antiemesis, antiemetic, emesis, emetic, postoperative nausea and vomiting, PONV, glucose, glucose response, adverse events, wound infection and wound healing. The detailed search strategy was shown in Supplementary file http://markummitchell.github.io/engauge-digitizer/).Two researchers (Q.P. and X.L.) independently assessed the quality of each included articles and extracted the data according to the predefined inclusion and exclusion criteria. Any discrepancy was resolved by a consensus process involving a third author (H.L.). The following data were extracted from each article: the author, publication year, study design, allocated groups, sample size, intervention, and outcomes. When the data were presented as median or graphs, we tried to contact the corresponding author by email for the raw data, if no response, we then transferred the data from median to mean ± SD . The evaluated items included selection criteria, comparability and outcome (cohort) or exposure (case-control). The maximum score was 9, and the trial with a score less than 7 was excluded.Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology was used to appraise the overall evidence- based quality of each outcome.I2 value, the levels of heterogeneity were defined as low when I2 ≤ 25%, moderate when I2 ranges 25–50%, and high when I2 > 50%. The fixed-effect model was used when I2 ≤ 50%, and the random-effect model was used when I2 > 50%. Subgroup analysis and sensitivity analysis were performed to explore the source and size of heterogeneity among studies when necessary. The egger test was used for publication bias evaluation, and there was no statistical publication bias if P > 0.05 from egger test.The meta-analysis was conducted using Stata software (version 14). The calculation of effect size for blood glucose was mean differences (MD) with 95% confidential index (CI), the units of glucose were mmol/L and mg/dL, and in the forest plot, the units of glucose level was presented as mmol/L. The MD value of glucose levels at different time points between dexamethasone and control, and the MD value of peak glucose level within 24 hours of surgery between dexamethasone and control represent the magnitude of blood glucose rise caused by dexamethasone. The calculation of effect size for insulin requirement was standardized mean differences (SMD) with 95% CI. The effect size for dichotomous data was presented as odds ratio(OR) with 95% CI. The data of glucose levels at each time point (pre/intra/postoperatively) were expressed as mean, and the trend of glucose changes was presented. The between-study heterogeneity was determined by Our search strategy identified 4511 citations from the databases and other sources. The full versions of 41 articles were retrieved after screening and conducting a detailed selection process. Finally 16 articles . Compared with control, dexamethasone could increase glucose level intraoperatively , at the end of surgery , on POD 1 , and on POD 2  , and at the end of surgery , but there was no significantly differences between groups on POD 1 .Subgroup analysis for RCTs showed that dexamethasone could increase glucose level intraoperatively , on POD 1 , and on POD 2 .Subgroup analysis for cohort studies showed that dexamethasone could increase glucose level at the end of surgery   Fig. , which iI2 = 48.1%, P = 0.000). The cohort study revealed no significant difference between groups (P = 0.539).Subgroup analysis for RCTs showed that dexamethasone increased peak glucose level compared with control . Three cohort studies ; and those on POD1 were from only 1 study .One RCT   Fig. .Fig. 5FoP < 0.05).Two RCTs , except the result of peak glucose level (P < 0.05), see Table Egger test showed that there was no significant publication bias between articles for all outcomes , the increase of glucose level at each time point perioperatively was even lower, and dexamethasone had no effect on wound healing. Thus, dexamethasone with a single dose could be safely used for PONV prophylaxis in diabetic patients.Additional file 1: Supplemental file 1. Detailed search strategy in databases.Additional file 2: Suppl table 1. The trend of mean glucose level [mg/dL(mmol/L)].


PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios ([product]/[substrate]) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA,  The prevalence and morbidity of non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated fatty liver disease (MAFLD) , is incrDietary fatty acids (FA) play an important role in the development of NAFLD . The lipceic.hrc@salud.madrid.org, Approval Number 097/17). All patients gave written informed consent before initiation of the study procedures. All methods were performed in accordance with the relevant guidelines and regulations.This was a prospective cohort study at Hospital Universitario Ramón y Cajal in Madrid (Spain) from January 2018 to December 2018. HIV-uninfected participants diagnosed with NAFLD were recruited at the Metabolic Liver Disease Clinic. HIV-infected participants receiving suppressive antiretroviral therapy were recruited at the HIV Clinic. We included those who presented elevated liver enzymes for at least two determinations, separated by six months. Any transaminase  level above the upper limit of normal in our laboratory was considered. HIV-infected participants were receiving antiretroviral therapy for at least 1 year with undetectable viremia in the last 6 months. All participants underwent abdominal ultrasound and a screening analysis for liver disease. Diagnosis of NAFLD was established by ultrasound confirmation of steatosis and exclusion of other aetiologies of chronic liver disease. Exclusion criteria included viral hepatitis; alcohol abuse (defined by >30 g daily in men and >20 g daily in women); cocaine, heroin, or designer drug abuse; other known liver diseases ; isolated alkaline phosphatase alteration; recent drug toxicity; impossibility of cannulating a peripheral blood line if a liver biopsy is required; pregnancy or desired pregnancy; decompensated liver disease or hepatocarcinoma; and any other comorbidity that, at the investigator’s discretion, could prevent correct compliance with the study protocol. Clinical information was collected through the clinical interview at the baseline visit of the study, together with the review of the medical history recorded in the electronic medical record. Metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) third report . The stuFatty acid methyl esters (FAME) were prepared directly from plasma and serum samples (200 μL), without previous lipid extraction, following the acid-base methylation method as described by Castro-Gomez et al. . Two indFAME analysis was carried out on an Autosystem chromatograph , fitted with a flame ionization detector (FID). Helium was the carrier gas with a column inlet pressure, set at 20 psi and a split ratio of 1:20. The injection volume was 0.5 μL of the sample. The column, a VF-23ms-fused silica capillary column  was held at 60 °C for 1 min after injection. Temperature-programmed at 10 °C/min to 130 °C, then at 3 °C/min to 170 °C, and finally at 10 °C/min to 230 °C, where it was held for 5 min. The injector and detector temperatures were set at 250 °C and 270 °C, respectively. For FAME determination and quantification, anhydrous milk fat  and FA standards  were used. FAME levels in plasma and serum were compared without significant measurement differences; the present work shows comparisons of plasma samples. FA concentrations were expressed as molecular percentages (g FA/100 g fat).Baseline characteristics of patients with and without HIV infection were compared with the Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. We used ratios ([product]/[substrate]) as indirect estimators of desaturases and elongases’ activity, in accord with previous literature . We perfWe included 53 participants diagnosed with NAFLD, of whom 31 (58%) were PLWH and 22 (42%) were HIV-uninfected . Particitrans-palmitoleic (trans C16:1), and behenic (C22:0) acids, and a lower concentration of lignoceric (C24:0) acid. Moreover, they had a marginally significant higher concentration of myristic (C14:0) and pentadecanoic (C15:0) acids. These results are seen graphically in trans-palmitoleic, and behenic acids and a lower concentration of lignoceric acid in PLWH.This prospective study found a similar plasma FA profile in people diagnosed with NAFLD, regardless of HIV status. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, Our findings agree with previous work studying plasma FA profiles in patients with NAFLD ,16. All It is postulated that PLWH are at increased risk for NAFLD due to numerous factors associated with HIV infection. These include sustained immune activation and inflammation, and toxicity of antiretroviral therapy, especially for nucleoside reverse transcriptase inhibitors (NRTIs) used in the past. Other antiretroviral drugs, such as efavirenz, also present an increased risk of chronic liver disease , while melongation of very long chain FA (ELOVL) microsomal enzyme family, which regulates the elongation of SFA and MUFA. Both ELOVL1 and ELOVL6 are biomarkers associated with an increased risk of NAFLD in the HIV-negative population with metabolic syndrome [Strikingly, despite a lower prevalence of risk factors, PLWH have a plasma FA profile comparable to non-HIV NAFLD controls. As mentioned, however, some significant differences were observed, especially lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimate the activity of the elongases ELOVL1 and ELOVL6, respectively ,20. Elonsyndrome . These esyndrome . It was syndrome .Our study has limitations. FA distribution in plasma has more variability than that studied in erythrocyte membranes. However, data may still be compared: the characteristics of dietary patterns were similar in both groups, and we performed adjusted analyses. The groups showed differences in variables such as sex, BMI, diabetes mellitus, and metabolic syndrome. Statistical models were adjusted for sex and BMI. We used ratios to estimate elongases activity but did not measure enzyme expression. This method has been widely used in the literature, so we consider the estimates to be valid. However, the exploratory nature of the data and the restricted sample size demands caution when interpreting the results.We found that although PLWH present a different classical risk factor profile than HIV-uninfected individuals with NAFLD, the plasma FA profile is similar in both groups. However, we found differences that may be justified by the immunological characteristics of the HIV-infected population. Given the burden of NAFLD in PLWH, further studies are warranted to both advance knowledge and to control this disease.


This meta-analysis was performed to evaluate the anatomical efficacy and functional improvement of the conventional inverted internal limiting membrane (ILM), flap covering technique, and ILM flap filling technique for patients with idiopathic macular hole (MH).  Literature from Pubmed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were comprehensively retrieved. The primary outcomes included the MH closure rate and postoperative best-corrected visual acuity (BCVA). The secondary outcomes were the proportion of external limiting membrane (ELM) and ellipsoid zone (EZ) defect recovery. Pooled odds ratios (ORs), weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated using STATA 17.0 software. P=0.29). Similarly, the 2 techniques demonstrated equal effectiveness on the anatomical closure in MH with the average diameter smaller than 650 μm  and larger than 650 μm . However, compared with the filling technique, the inverted ILM flap covering technique was superior in postoperative BCVA  and presented a significantly higher proportion of reconstitution of ELM  and EZ .  7 studies that contained 139 eyes in the inverted ILM flap covering group and 121 eyes in the ILM flap filling group were selected. Pooled data suggested that the surgical treatment resulted in an overall MH closure rate of up to 97.12% (135/139 eyes) in the inverted ILM flap covering group and 99.17% (120/121 eyes) in the filling group, with no significant difference between the 2 groups (OR = 1.98, 95% CI: 0.55 to 7.09, and  The inverted ILM flap covering technique was associated with the superior reconstitution of outer layers of the retina, including ELM and EZ, and more improvement in postoperative BCVA than the ILM flap filling technique. An idioa et al.  introducIn the conventional ILM flap procedure, known as “inverted ILM flap covering,” the ILM is peeled circumferentially to the edge of the hole; after trimming the perimeter, the central remnant of ILM is massaged and then inverted on the hole to cover it . AfterwaThe ILM flap technique has displayed gratifying superiority in anatomical and functional recovery since it was innovatively described for the treatment of MH , 11. Curhttps://prisma-statement.org/) [∗” OR “macular break∗” OR “MH” AND “inverted internal limiting membrane” OR “inverted ILM” OR “ILM covering” OR “ILM insertion” OR “ILM transplantation” OR “ILM transposition” OR “ILM plug.” No language restrictions were applied. The search results were imported into reference management software  for careful screening. Two assessors (MYT and YQG) deleted duplicate documents, sifted through relevant reports, and reviewed the remaining studies by reading the full text of the literature independently. Besides, their reference lists were also searched for available literature.This meta-analysis corresponded with the Cochrane Handbook for Systematic Reviews of Interventions  and Prefnt.org/) . ElectroThe literature according to the following criteria were included: (1) patients diagnosed with IMH, (2) intervention measure was technique containing the inverted ILM flap covering and ILM flap filling procedure, (3) one of the following outcomes should be reported, including the anatomical hole closure rate  detection), or preoperative and postoperative best-corrected visual acuity (BCVA) expressed as the logarithm of the minimal angle of resolution (logMAR), and (4) study design such as prospective randomized controlled trials (RCTs), prospective non-RCT, and retrospective comparative studies were included. Exclusion criteria were as follows: (1) patients complicated with macular retinoschisis, retinal detachment, ocular inflammation, and history of vitrectomy, (2) studies without ILM flap covering or ILM flap filling group, (3) the data were not available for meta-analysis, and (4) case reports, surgical technique, and review literature.https://automeris.io/WebPlotDigitizer) [Two investigators (MYT and GQW), respectively, screened the literature and extracted relevant information manually or by the semiautomated extraction tool WebPlotDigitizer  . The avaThe quality of the selected RCT studies was assessed by using the Cochrane risk of bias assessment tool . Six domP < 0.05 was considered to indicate statistical significance. Statistical heterogeneity between clinical trials was assessed by the χ2 test, with P > 0.05 and I2 < 50%, indicating no significant heterogeneity, and a fixed-effects model was performed to assess. Otherwise, a random-effects model was applied. Sensitivity analysis was utilized to verify the credibility of the statistical conclusion. Besides, the funnel plot, Begg's and Egger's correlation test were conducted for publication bias.All statistical analyses were conducted with Review Manager  and STATA software . The odds ratios (ORs) and 95% confidence intervals (CIs) were reported for dichotomous variables, while the weighted mean difference (WMD) with 95% CI was calculated for continuous variables such as BCVA. The inverse variance (IV) or the Mantel–Haenszel (MH) method was used to deal with the clinical statistics. The number of identified articles through database searching amounted to 761. Of these, 402 articles were duplicates, and 359 articles remained for preliminary review by reading the titles and abstracts. After further screening and retrieving, 343 articles were discarded for irrelevant topics, reviews, letters, case reports, surgical techniques, and infeasibility for retrieval. A total of 14 studies were assessed for eligibility by reading the full text. 4 reports were excluded, including 3 articles for complications except for MH and 1 record for case series. Subsequently, 7 studies (260 affected eyes) met the inclusion and exclusion criteria and were included in the final meta-analysis , 23, 24.I2 = 0%, P=0.95), the fixed-effects model was applied for statistical analysis. The data showed that the ILM flap filling group possessed a better restorative tendency compared with the inverted ILM flap covering group, but the statistical difference was of no significance, with the anatomic success rate of up to 97.12% (135/139 closed eyes) in the inverted ILM flap covering group and 99.17% (120/121 closed eyes) in the ILM flap filling group  (μm as the reclassification standard of the MH size proposed by Ch'ng and his colleagues was carried out [μm (5 articles) was 96.39% and 98.73%, respectively. Similarly, the closure rate was 98.21% and 100.00% in the subgroup of MH larger than 650 μm (2 articles), indicating an absence of significant difference in 2 subgroups   . Consideried out . The poo 650 μm) .I2 = 62.19%, P=0.03). The pooled data did not indicate any significant difference between the 2 groups  (I2 = 37.47% and P=0.17), the postoperative BCVA  in the inverted ILM flap covering group was significantly better when compared to the ILM flap filling group  . Neverthng group .I2 = 5.23% and P=0.37) and EZ reconnection (I2 = 45.43% and P=0.14). The respectively calculated OR was 0.02 (95% CI: 0.00 to 0.08) and 0.11 (95% CI: 0.04 to 0.32) for the proportion of ELM and EZ fully restored. The analysis demonstrated that the inverted ILM flap covering group was associated with a significant efficacy both in ELM and EZ complete recovery compared to the group treated with the ILM flap filling method   .P=0.13 and P=0.23 for MH closure rate analysis, P=0.81 and P=0.98 for preoperative BCVA assessment, and P=0.81 and P=0.51 for postoperative BCVA evaluation. Outcomes of sensitivity analysis demonstrated the satisfactory stability of the calculated meta-analysis results, for which the new statistical results were not statistically different from the initial study results after erasing any one of the studies  in the subgroup that reported the surgical outcomes. Since a large number of studies reported the prompt and efficient reconstruction of the super large MH treated with the filling technique [However, it was still imprudent to conclude that both 2 surgical techniques performed equal effectiveness on MH over 650 echnique , 32, it Based on the results of the present analysis, the preoperative BCVA was of no significant difference between the 2 groups, which indicated that the preintervention effects were balanced and the postoperative BCVA was comparable. Besides, the improvement of postoperative BCVA in inverted ILM flap covering patients was better than that in patients with ILM flap filling. Except for Rossi et al.'s study, all 6 studies undoubtedly suggested that the covering technique obtained a clear superiority in visual gain in contrast to the filling technique. The result of visual prognosis is probably attributable to the reconstitution of the outer retina, including ELM and EZ, where photoreceptors align and reconnect with retinal neurons –36. EquiG (BBG), and triamcinolone acetonide (TA), have been reported to have potentially toxic effects on the retina [However, there are several concerns related to the ILM flap filling technique. On the one hand, filling the ILM flap sheets into the hole might be associated with mechanical injury of RPE in operation. Moreover, the intrusive ILM flap could become an obstacle during the repair period, thus throwing the neurosensory retina rearrangement into disorder . On the e retina –43. The There were several limitations demonstrated when explicating the results of this meta-analysis. First, the number of included studies providing available data was limited, and the inadequate quantity of accessible data affected the ultimate results. Second, the limited number of cases and relatively short follow-up of the patients resulted in a deficiency of additional information such as visual outcomes, recurrence rate, and operative complications in the long run. Therefore, we were not able to conduct a comprehensive analysis without these important outcome indicators. Third, the potential deviation resulting from a shortage of information about the duration of MH, vital dye, and the final endotamponade ought to be taken into consideration when the statistical analysis was performed. Last, converting the information on the graphs to statistical data might bring extra bias.This meta-analysis provided evidence that the inverted ILM flap covering technique could contribute to the superior reconstitution of outer layers in the retina, including ELM and EZ, and consequently more improvement in postoperative BCVA than the ILM flap filling technique, although both obtained significantly high anatomical closure success of MH. However, more randomized and prospective studies with larger sample sizes and longer follow-up duration are necessary to confirm the efficacy of the inverted ILM flap covering technique.


As the primary source of dietary energy, improving fat digestibility can have positive impacts on performance and profitability in pig production. Use of lysolecithin to improve fat and other nutrient digestibility may be able to increase the growth rate and efficiency of growing pigs. In the present study, a combination of lysolecithin, synthetic emulsifiers and monoglycerides was able to significantly increase nutrient and amino acid digestibility in growing pigs, driving significant increases in growth, efficiency and the economics of production.p < 0.05). Average uplift in AA digestibility as a percent of the PC was +1.88%; with greatest improvement for histidine (+4.22%). LEX supplementation effectively compensated energy deficiency of low-density diet and provided additional ME improvement compared to the PC diet (p < 0.05). A second study was conducted to evaluate LEX dose response on the growth performance of pigs fed a low nutrient density diet. Total 450 cross-bred pigs  and 210 females) [Duroc x (Large White x Landrace)] with an average initial BW of 7.19 kg were randomly allocated into 4 dietary treatments: (1) a positive control (PC) formulated with standard specifications, (2) a negative control formulated with −100 kcal ME/kg and −2.5% AA content vs. the PC (NC), (3) NC + LEX at 250 g/t (NC + 250) and (4) NC + LEX at 500 g/t (NC + 500). Results showed significant improvement with LEX supplementation on the final BW, average daily gain (ADG) and feed conversion ratio (FCR) of pigs of >50 kg body weight. Across the study, NC + 500 significantly increased ADG vs. PC and NC, and significantly reduced FCR compared to all other treatments. FCR of negative control diets improved by 9 and 15 points with the supplementation of 250 g/t and 500 g/t of LEX, respectively (p < 0.05). FCR in the NC + 250 diet was statistically similar vs. PC, which was significantly reduced compared to the NC. Taken together, these studies demonstrate that the addition of an absorption enhancer containing a combination of lysophospholipids, monoglycerides and synthetic emulsifiers can improve growth performance in growing pigs, driven by increased nutrient digestibility and retention.Two studies were conducted to determine the impact of an absorption enhancer containing a combination of lysophospholipids, monoglycerides and synthetic emulsifiers (LEX) on apparent ileal digestibility, metabolizable energy (ME), and growth performance of growing pigs. In the digestibility study, 12 male crossbred [Duroc x (Large White x Landrace)] pigs with an initial body weight (BW) of 30 kg were randomly allocated to two dietary treatments: (1) a positive control (PC) receiving standard diets formulated to 3100 kcal ME/kg, and (2) a negative control formulated with −100 kcal ME/kg and −2.5% AA content vs. PC and supplemented with LEX at 500 g/t. Apparent ileal digestibility of essential AA was significantly increased for lysine, methionine, threonine, histidine, isoleucine and phenylalanine in the LEX treatment ( Efficient fat utilization has great economic significance in maintaining profitable pig production since fat is both an important and expensive feed ingredient . The praLysophospholipids can improve the emulsification of feed fats, advance mixed micelle formation, and enhance the absorption of nutrients by increased cell membrane permeability ,6,7,8. ZPrevious research has shown the potential of combining lysophospholipids with other active ingredients such as monoglycerides and synthetic surfactants in improving the absorption of nutrients . In poulBoth studies were carried out at the Research Station of Institute of Animal Sciences for Southern Vietnam in Ho Chi Minh City. All experimental procedures were in line with commercial practices, compliant with all local animal welfare legislation, and approved by the Institute of Animal Sciences for Southern Vietnam in Ho Chi Minh City.® Extend, Kemin Industries, Des Moines, IA, USA (LEX)). Ingredient and nutrient composition of the experimental diets is shown in A total of 12 weaned piglets (30 kg live weight) were allocated to two treatments and housed in individual metabolism cages. The positive control (PC) diet was a commercial feed containing 3100 kcal ME/kg, formulated to meet all nutrient requirements. The remaining diet was reformulated to −100 kcal ME and −2.5% amino acid compared to the positive control and supplemented with 500 g/t of a combination of lysophospholipids, monoglycerides and synthetic emulsifiers  was added at 0.2% (DM basis) to diets as an indigestible marker. All feed refusals and faeces were collected daily and weighed and stored at −20 °C prior to subsampling. At the end of collection period, subsamples  were taken after carefully mixing 5-day collected feed refusals and faeces. Chromium oxide (Cr2O3 concentration in the diet (g/kg); If the Cr2O3 concentration in ileal digesta or faeces (g/kg).Digesta samples were weighed, homogenized and frozen at −20 °C. Sub-samples of feed refusals and faeces were dried at 60 °C; and digesta samples were freeze-dried prior to chemical analyses. Samples were subsequently ground and analyzed in duplicate. Chemical analyses including amino acid analysis were run at Institute of Animal Sciences in Ho Chi Minh City according to AOAC methods (2002 and 2006) ,19. CP wThe ME of the diets was calculated as follows :DE = DigFour hundred and fifty pigs ([Duroc × (Large white × Landrace)]) with an average initial weight of 7.19 kg (SD = 0.2) and of similar age of 28 days were randomly allocated according to gender to pens. Fifteen pigs  per pen were randomly allocated to one of the four dietary treatments with different levels of supplements as follows: (1) a positive control diet formulated to meet commercial specifications (PC), (2) a negative control (NC) formulated with 100 kcal ME/kg less ME and 2.5% lower amino acid content compared to PC, (3) NC supplemented with 250 g/t of LEX (NC + 250), and (4) NC supplemented with 500 g/t of LEX (NC + 500).® EXTEND . All pigs were provided with ad libitum access to feed and water through a self-feeder and nipple drinker, respectively. Before the study, from weaning at 28 days of age, all pigs were fed a common corn–soybean meal-based diet formulated to meet the nutritional requirements suggested by National Research Council . Ingredient and nutrient composition of the experimental diets is shown in Pigs were housed in pens and fed the experimental diets for 140 days. Live body weight (BW) was recorded at initial (28 days of age), 56, 112 and 168 days of age. Feed intake was monitored daily to calculate average daily feed intake (ADFI) per phase and overall. Feed refusals (from the previous day) were collected every morning before daily feeding. Collected feed was then dried to attain a moisture content of 13% and weighed. Average daily weight gain (ADG) and feed conversion ratio (FCR) were then calculated from overall bodyweight gain and total feed intake. At the end of the experiment, backfat thickness at P2 was measured by Aloka machine.Using the method of Wealleans et al. , performTotal bacterial count and coliform counts were determined using standard methods ,25. Totap < 0.05 was considered statistically significant; p < 0.1 was considered to indicate a near-significant trend.Data were analysed by ANOVA using Minitab Statistical Software version 16.2.0 (2010). Differences between means were tested by using Tukey’s Honest Standard Difference. An analysis of variance was done according to the following model:p > 0.05); whereas the ME intake was significantly lower in the PC compared to NC + 500 (p < 0.05) due to higher ME concentration (p < 0.05) (p < 0.05).The intake of dry matter and crude protein did not differ significantly across the treatments ( < 0.05) . HoweverLEX supplementation improved the ileal digestibility of crude protein and essential amino acids, as shown in The results of BW, DMI, ADG and FCR in three growth stages are shown in p < 0.05). Reduction in ME and amino acid content resulted in lower growth performance of NC compared to the PC (p < 0.05), while LEX supplementation on top of NC diets resulted in significant improvement in body weight, and average daily gain (ADG) as the pigs grew older (112 days and beyond). Final BW of pigs fed NC + 500 was higher than that of both the NC and PC (p < 0.05). Daily feed intake in pigs across all treatments were not significantly different (p > 0.05). Feed conversion ratio (FCR) showed differences across treatments at 56–112 and 112–168 age days. At 56–112 days, NC + 500 resulted in a 14 point improvement in FCR compared to the NC group during both the 56th–112th day period and 112th–168th day period (p < 0.05).There was a significant difference in the BW of pigs at 112 and 168 days across the different treatments (p < 0.05). Supplementation of LEX facilitated improvement in growth performance with the most significant effect produced by LEX at 500 g/t. Feed conversion ratio (FCR) of negative control diets was improved by 0.09 and 0.15 with the supplementation of 250 g/t and 500 g/t of LEX, respectively (p < 0.05). There was no significant difference in backfat thickness between treatments on day 168. Likewise, there was no significant difference in feed intake between treatments throughout the study.Growth performance for the entire study period and the backfat thickness at slaughtered final weight are presented in Reformulation of growing pig diets and supplementation with LEX also demonstrated feed cost savings compared with the PC. NC + 250 resulted feed cost savings of 10.76 $/t for the starter diet, 9.23 $/t in the grower and 4.71 $ per tonne in the finisher compared to the positive control . LikewisThe average profit margin per pig was also substantially increased for both NC + 250 and NC + 500 compared to the positive control, with pigs fed the higher dose of LEX achieving increased profits of almost 8 USD per pig more than the positive control. When reformulation and improved performance following supplementation with LEX are considered, the changes resulted in improved profit per tonne of feed produced of 15.33 and 26.22 USD for 250 and 500 g/t, respectively.p > 0.05). It appeared that supplementing LEX in pig diets could help to improve digestibility a enhance useful microbial flora of pig intestine.Microbial analysis of faecal samples showed the highest total bacteria count and coliform count for samples collected from pigs fed with the commercially relevant PC diet . There wSeveral factors limit the digestion and absorption of lipids including the age of animals, type of fat, and emulsification of lipids within the gastrointestinal tract ,26,27. GThe beneficial effect of lysophospholipids on all three steps of the fat digestion process  has been extensively researched . Wealleap < 0.05). Previous studies conducted on weaning and lactating pigs have shown similar results: Jones et al. [The major finding from present study is the ability of LEX to improve the utilisation of metabolizable energy, dietary nutrients and amino acids by growing pigs. There was a significant increase in the digestibility of essential amino acids  with the use of LEX p < 0.0. Previous et al.  reporteds et al. . The nuts et al. ,11. An is et al. ,14. TherThe improved emulsification of fats could not only enhance the digestion of the lipids but also of other nutrients. For example, Honda et al.  found thLysophospholipids supplementation has been reported to have beneficial effects on gut microbiota, integrity and gene expression. Polycarpo et al.  found reThe present study showed that the addition of LEX significantly increased the performance of growing pigs fed lower nutrient dense diets, which reinforces the findings of previous studies that reported beneficial effect of lysophospholipid supplementation on the performance of weaning pigs . HoweverLysophospholipids in combination with monoglycerides and synthetic surfactants (LEX) improved the nutrient digestibility and growth performance of pigs fed low nutrient dense diets. Supplementation of LEX could be used to improve growth performance and profitability of commercial pig production.


The xyloglucans of all aquatic Araceae species examined had unusual structures compared with those of other non-commelinid monocotyledon families previously examined.Lemna minor was earlier shown to have xyloglucans with a different structure from the fucogalactoxyloglucans of other non-commelinid monocotyledons. We investigated 26 Araceae species (including L. minor), from five of the seven subfamilies. All seven aquatic species examined had xyloglucans that were unusual in having one or two of three features: < 77% XXXG core motif [L. minor (Lemnoideae) and Orontium aquaticum (Orontioideae)]; no fucosylation ; and > 14% oligosaccharide units with S or D side chains [Spirodela polyrhiza and Landoltia punctata (Lemnoideae) and Pistia stratiotes ]. Orontioideae and Lemnoideae are the two most basal subfamilies, with all species being aquatic, and Aroideae is the most derived. Two terrestrial species [Dieffenbachia seguine and Spathicarpa hastifolia ] also had xyloglucans without fucose indicating this feature was not unique to aquatic species.The aquatic Araceae species The online version contains supplementary material available at 10.1007/s00425-023-04071-w. Xyloglucans (XGs) are a family of non-cellulosic polysaccharides (hemicelluloses) that occur in the primary cell walls of all land plants (embryophytes) and in the most recently diverged lineages of their ancestors, the charophycean green algae Fry . Howeverd-glucopyranose (β-d-Glcp) residues with some of these having an α-xylopyranose (α-Xylp) residue attached to them at O-6. Other substituents may be present on some of the α-Xylp residues, giving a number of different side chains on the glucan backbone. A single-letter code is used to describe the structures of these side chains -linked β- → 4-linkO-6 Fig. , with thendo-(1 → 4)-β-glucanase (XEG), or less specifically with an endo-cellulase [endo-(1 → 4)-β-glucanase] and to identify and quantify the oligosaccharides released   XG included XXGG, XSGG, XLGG and LSGG  Harris . These XAllium cepa (onion), A. sativa (garlic) and their hybrid  are fucogalactoxyloglucans similar to those in the primary cell walls of most eudicotyledons . However, in contrast to Poaceae XG, it was also established that the XGs of Acorus, which comprises two emergent aquatic species. The Alismatales is a sister to the rest of the monocotyledons and consists of the large family Araceae and 13 smaller families. The liliids are composed of five orders in phylogenetic sequence: Petrosaviales, Pandanales , Dioscoreales (yams), Liliales , and Asparagales . The Asparagales is a sister to the fourth group, the commelinid monocotyledons, first recognized chemically and histochemically by the presence of ester-linked ferulic acid in their primary cell walls  with pulsed amperometric detection (PAD) and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) , which had some XXGn core motif (23%)  although mostly XXXG core motif (77%) and a much smaller proportion (6%) of the fucosylated oligosaccharides (XXFG and XLFG). The species examined in the Liliales, Dioscoreales, and Pandanales also had XGs with mostly the XXXG core motif, but with some of the XXGn core motif , with the fucosylated oligosaccharides XXFG and XLFG being released.In their study of monocotyledon XGs, Hsieh and Harris  treated Zantedeschia aethiopica and the aquatic species Lemna minor. Z. aethiopica XG had a similar XGO profile to eudicotyledon fucogalactoxyloglucans with only the XXXG core motif, although the total percentage for the two fucosylated XGOs was quite low at 11%. However, the XGO profile of the floating aquatic duckweed species Lemna minor was quite different, with a high proportion of the XXGn core motif (80%) and neither of the two fucosylated XGOs, XXFG and XLFG.No representative of the order Petrosaviales was examined, but two species were examined in the Alismatales both in the aroid family Araceae: the terrestrial species Lemna and four other genera) formerly regarded as a separate family, Lemnaceae, are part of the Araceae. Cusimano et al.  and species in the Rheophytes clade  in the aquatic, early diverging subfamily Lemnoideae and Orontium aquaticum in the aquatic, basal subfamily Orotioideae  and Cryptocoryne aponogetonifolia and Lagenandra ovata (Rheophytes clade)  Fig. . The othd Harris  except aIn the present study, we examined 26 species of Araceae. The species, clade numbers and names, as used by Cusimano et al. , the souAIRs were isolated following the procedure of Popper et al.  as modif4 (10 ml) to prevent possible β-oxidation of the polysaccharides and alkaline peeling. The suspension was then filtered using Miracloth, and the filtrate cooled on ice for 20 min before it was adjusted to pH 5.0 by adding 17.4 M acetic acid. One drop of toluene was added to the solution to stop microbial growth, before it was dialysed, first against tap water at room temperature for 24 h, and then against distilled water for 1 h. The resulting dialysate was freeze dried.This was carried out as described by Hsieh and Harris , 2012. TPaenibacillus sp.  (10U) in 100 mM sodium acetate buffer (pH 5.5) at 40 °C for 20 min. The samples were then heated to 100 °C for 2 min to stop the reaction. Buffer-only control incubations were also carried out.The extracted non-cellulosic polysaccharide preparations (1–2 mg) were incubated with a high purity, recombinant XEG (GH5) (EC 3.2.1.151) from L. punctata was an exception in that it was treated with recombinant XEG from A. aculeatus (EC 3.2.1.151) exactly as described by Hsieh and Harris (The sample (2 mg) of extracted non-cellulosic polysaccharides from the AIR of d Harris , 2012.+ of the oligosaccharides. An exception was the sample from L. punctata for which the spectrometer described in Hsieh and Harris (−1 in water) and NaCl , and an aliquot (1 µl) was dried onto a sample plate. A reference preparation of tamarind XGOs (Megazyme) (10 µl)  was treated in the same way. The spectrometer was operated in the reflectron mode at an accelerating voltage of 20 kV with a delay time of 200 ns. For each spectrum, data from 1000–2000 laser shots were averaged using Bruker flexAnalysis software. A 6 M NaOH extract of an AIR of hypocotyls of the eudicotyledon Vigna radiata (family Fabaceae) was also treated with the XEG from Paenibacillus sp. as above and, after mass spectrometry, sodium adduct ions [M + Na]+ of the oligosaccharides were compared with those obtained from a similar extract treated with the XEG from A. aculeatus in the study of Hsieh and Harris (+adduct ion (on a height basis) as a percentage of the total intensities of ions identified as [M + Na]+ adduct ions of XGOs; absolute response factors were not determined.A MALDI-TOF mass spectrometer  was used to identify the various XGOs by determining the molecular weights of the sodium adduct ions [M + Na]d Harris , 2012 wad Harris . The XGOPaenibacillus sp. from the 6 M NaOH extract of the AIR of the reference eudicotyledon V. radiata had high proportions of sodium adduct ions [M + Na]+ corresponding to XXXG, XXFG and XLFG  and was similar to the profile released by the XEG preparation from A. aculeatus from a similar extract from the same species , accounted for > 76%. Most profiles had the XXXG in high proportions, XLXG/XXLG in varying proportions, and the fucosylated XXFG. Only a few profiles in subfamily Monsteroideae and subfamily Aroideae, Dracunculus clade also had XLFG, and the profiles of five species  had neither XLFG nor XXFG. The profiles of some species had XLLG, but in varying proportions. Except for one species Arum pictum , the XGs of all had some repeating XXGn core motif, with most of the XGOs with this core motif being XXG and XXGG. Although XXG oligosaccharides are likely to be released directly from the XGs, it is possible they result from further action of the XEG preparation on XXGG as it has been found that the Paenibacillus sp. XEG preparation can degrade XSGG into XSG  in the basal subfamily Orontioideae, and L. minor (23% XXXG core motif) in the subfamily Lemnoideae, which is sister to the rest of the Araceae subfamilies , Spirodela polyrhiza and Landoltia punctata had 94% and 87% XXXG core motif, respectively. The xyloglucans of O. aquaticum, S. polyrhiza and L. punctata, but not L. minor, were fucosylated, although only XXFG was released, and except for S. polyrhiza, in only small proportions. The XGO profiles of the XGs of L. punctata and S. polyrhiza, but not L. minor, were also unusual in having significant percentages of XGOs containing S/D side chains, with L. punctata containing XXSG/XXDG (22%) and XLSG/XLDG (11%), and S. polyrhiza containing only XXSG/XXDG (15%).Two of the Araceae species in which the XXXG core motif accounted for < 77% were aquatic species in the two earliest emerging subfamilies, Orontioideae and Lemnoideae. These two species had XGs with particularly low percentages of this core motif and were A. gracile (subfamily Pothoideae) contained only 62% XXXG core motif and was the third exception in the Araceae species examined to contain < 77%. Another species in the same genus, Anthurium andraeanum, had 80%. The XG of A. gracile was also unusual in being the only species in the two subfamilies to yield an XGO containing S/D side chains, XXSG/XXDG (8%).The profiles of the XGs in the species examined of the two subfamilies that form the Bisexual Climbers clade Fig. , PothoidZantedeschia clade, the Rheophytes clade, and the Dracunculus clade.Because the most derived subfamily of Araceae, Aroideae, is large, we consider separately the XGO profiles of the XGs of the species in the three major clades, the Zantedeschia clade, the four species examined had 79–87% XXXG core motifs, but two of these D. seguine and S. hastifolia, both in subclade Spathicarpeae, yielded no fucosylated XGOs and the other two species Aglaonema costatum (subclade Aglaonemateae) and Philodendron hederaceum (subclade Philodendron) yielded XXFG , but no XLFG. The xyloglucans of P. hederaceum and D seguine also yielded XXSG/XXDG (3%) and XLSG/XLDG (9%), respectively.In the C. aponogetonifolia and L. ovata (subclade Cryptocoryneae), are aquatic and their XGs had 94 and 97% XXXG core motifs, respectively, but yielded no fucosylated XGOs and no XGOs with S/D side chains.In the Rheophytes clade, both species examined, Dracunculus clade, three of the examined species, Amorphophallus dunnii, Syngonium auritum and Xanthosoma sagittifolium, are in the Amorphophallus subclade and the rest in the Pistia subclade. Those in the Amorphophallus subclade had XGs with 82–86% XXXG core motifs, and all yielded both XXFG and XLFG, with S. auritum yielding particularly high total percentages (23%) of both fucosylated XGOs (15% XXFG and 8% XLFG). The XGs of each species in this subclade yielded a small percentage of XGOs with S/D side chains: A. dunnii yielded XLSG/XLDG (2%), and S. auritum and X. sagittifolium yielded XXSG/XXDG . The six species examined in the Pistia subclade had XGs with 77–100% XXXG core motifs, with Arum pictum having 100% and the aquatic species Pistia stratiotes having 92%. The XGs of all the examined species yielded fucosylated XGOs, with all but three yielding both XXFG and XLFG. The exceptions yielded only XXFG, but only in small proportions for P. stratiotes (6%) and Colocasia esculenta (1%). However, this subclade had species with the highest total percentages of both fucosylated XGOs (XXFG and XLFG), with A. pictum yielding 34% and Alocasia macrorrhizos 28%. The only species in this subclade to yield XGOs with S/D side chains was the aquatic species P. stratiotes, which yielded XXSG/XXDG (3%) and a high percentage (35%) of XLSG/XLDG.In the O. aquaticum (subfamily Orontioideae) had XG with < 77% XXXG core motif. L. minor (subfamily Lemnoideae) had XG with both < 77% XXXG core motif and no F side chains. S. polyrhiza and L. punctata XG yielded > 14% XGOs with S/D side chains. In subfamily Aroideae, the XG of P. stratiotes (clade Dracunculus) also had > 14% XGOs with S/D side chains, whereas in the Rheophytes clade C. aponogetonifolia and L. ovata the XG had no F side chains. However, the lack of F side chains as a feature is not unique to aquatic species as it also occurs in the terrestrial species D. seguine and S. hastifolia, both in the Zantedeschia clade (subclade Spathicarpeae) (see above).The XGs of the seven aquatic Araceae species examined all had one or two of the following three unusual features: < 77% XXXG core motif, no F side chains, or > 14% XGOs with S/D side chains. + with m/z 527 (Hex3), 629   were present in substantial proportions in the XGO profiles of some species (Table 4), m/z 923  , and m/z 1541 (Hex6Pent4). The structural identities of Hex3 and Hex4 and the source polysaccharide are unknown, but Steck et al. (Paenibaccillus sp. XEG preparation had (1 → 3),(1 → 4)-β-glucanase activity and released oligosaccharides with sodium adduct ions corresponding to Hex3 and Hex4, probably β-Glcp-(1 → 4)-β-Glcp-(1 → 3)-Glcp and β-Glcp-(1 → 4)-β-Glcp-(1 → 4)-β-Glcp-(1 → 3)-Glcp. The XX may be formed from some of the released XXXG oligosaccharides as Steck et al. (Paenibaccillus sp. XEG preparation released XX (m/z 629) as well as XG (m/z 494).In many of the species examined, sodium adduct ions of other oligosaccharides were found in addition to those of XGOs. Sodium adduct ions [M + Na]k et al.  reportedk et al.  found thn core motif. However, our hypothesis that the XGs of all aquatic Araceae species have low proportions (< 77%) of the repeating XXXG core motif [high proportions (> 23%) of the repeating XXGn core motif] and no F side chains, was not supported. The seven aquatic species examined in the present study had XGs that were unusual in having one or two of the following features: a < 77% XXXG core motif, no F side chains, or > 14% XGOs with S/D side chains. O. aquaticum in the basal subfamily Orontioideae had XG with < 77% XXXG core motif. The duckweed L. minor in the early diverging subfamily Lemnoideae had XG with both a < 77% XXXG core motif and no F side chains. Both O. aquaticum and L. minor had XGs with particularly low percentages of the XXXG core motif, 45% and 23%, respectively. The two other duckweed species examined S. polyrhiza and L. punctata had XGs that yielded > 14% XGOs with S/D side chains. In the most derived subfamily Aroideae, where the aquatic habit is a secondary acquisition  also had > 14% XGOs with S/D side chains, whereas in the Rheophytes clade C. aponogetonifolia and L. ovata the XG had no F side chains. However, XGs with no F side chains were not unique to these species in the Rheophytes clade, D. seguine and S. hastifolia, both terrestrial species in the Zantedeschia clade of subfamily Aroideae, had XGs with no F side chains. S/D side chains also occurred in the XGOs of XGs of a number of other Araceae species, but the percentages of these XGOs did not exceed 14%.The present results show that the XGs of the Araceae are mostly similar in structure to those of the other non-commelinid monocotyledons that have been examined in the orders Asparagales, Liliales, Dioscoreales and Pandanales -β-d-Galp present in F side chains , although all primary walls contained XGs only those of the phloem cells had F side chains  (Pfeifer and Classen f) form (side chain S) or in the pyranose (Arap) form (side chain D). As far as we are aware, S side chains have not previously been reported in XGs of monocotyledons, but they have been found in XGs of species in the eudicotyledon orders Solanales, Lamiales, and Gentianales  (family Oleaceae) in the Lamiales  in the Gentianales  Ceratopteris richardii, where only the gametophyte generation was examined, and Equisetum hyemale, where it occurred in only small proportions  residues are in the furanose  in the basal subfamily Orontioideae and of L. minor (77%) in the early emerging subfamily Lemnoideae. Such high proportions may occur only in the XGs of species in these subfamilies, whereas the XGs of the other two species examined in the Lemnoideae, S. polyrhiza and L. punctata had low proportions of the XXGn core motif, 6% and 13%, respectively. High proportions (> 14%) of XGOs with S or D side chains were also released from the XGs of S. polyrhiza and L. punctata, as well as from the XG of P. stratiotes in the derived subfamily Aroideae. Thus, there appears to be no clear-cut phylogenic trend in the XG structures of aquatic species in this family.In conclusion, our hypothesis was not supported. However, all of the aquatic species examined had XGs that were unusual in having either one or two of the following features > 23% of the repeating XXGSYH, JL, DW and PHL performed the experiment. SYH, JI, BI, HCL, MK, CHC, PHL, PJH and YH analysed the data. SYS, PJH and YH wrote the manuscript.Supplementary file1 (DOCX 1487 KB)Below is the link to the electronic supplementary material.


As the largest shallow freshwater lake in the North China Plain, Baiyangdian lake is essential for maintaining ecosystem functioning in this highly populated region. Sediments are considered to record the impacts of human activities.The abundance, diversity and metabolic pathways of microbial communities in sediments were studied by metagenomic approach to reveal patterns and mechanism of C, N, P and S cycling under the threat of lake eutrophication.Nocardioides (Actinobacteria), Thiobacillus, Nitrosomonas, Rhodoplanes and Sulfuricaulis (Proteobacteria).For instance, the abundance of Nocardioides were positively correlated to TN, EC, SOC and N/P ratio in pathways of phytase, regulation of phosphate starvation, dissimilatory sulfate reduction and oxidation, assimilatory sulfate reduction, assimilatory nitrate reduction and reductive tricarboxylic acid (rTCA) cycle. Many key genes in C, N, P, S cycling were closely related to the reductive citrate cycle. A complete while weaker sulfur cycle between SO42− and HS− might occur in Baiyangdian lake sediments compared to C fixation and N cycling. In addition, dissimilatory nitrate reduction to ammonia was determined to co-occur with denitrification. Methanogenesis was the main pathway of methane metabolism and the reductive citrate cycle was accounted for the highest proportion of C fixation processes. The abundance of pathways of assimilatory nitrate reduction, denitrification and dissimilatory nitrate reduction of nitrogen cycling in sediments with higher TN content was higher than those with lower TN content. Besides, Nocardioides with plural genes encoding key enzymes involved in nasAB and nirBD gene were involved in these pathways.Many genera, with plural genes encoding key enzymes involved in genes, belonging to Proteobacteria and Actinobacteria which were the most main phylum in bacterial community of Baiyangdian sediment were involved in C, N, S, P cycling processes, such as Nocardioides involved in the processes of assimilatory nitrate reduction, denitrification and dissimilatory nitrate reduction of nitrogen cycling may have important effects on nitrogen transformation. And ovetrifiers . The euttrifiers . Pesticitrifiers . It is ctrifiers . To the trifiers . It is dtrifiers ,b. The ctrifiers .In shallow lakes, eutrophication is widespread which leads to phytoplankton and algal blooms and then hypoxic or anoxic episodes when the organisms submerge and decompose, and is generally caused by increased P, N and organic matter . As the 2.2.1.2. Baiyangdian is the ecological hinterland of Xiong’an New Area. As a carrier of ecological resources and a sink of environmental load, water environment of Baiyangdian is tightly related to the ecological security of Xiong’an New Area. In our study, we want to basically reflect the whole physicochemical property of Baiyangdian Lake, so total 10 typical sediment samples (0–10 cm depth) which were intensively mixed of 4–6 buckets with grab bucket were collected during November 25 ~ 26, 2021. Specific sampling sites were marked as S1 to S10 in In northern China, Baiyangdian Lake is located in the center of Hebei province at 38°43′ to 39°02′ N, 115°38′ to 116°07′ E  with a w2.2.2Cr2O7; total nitrogen (TN) concentration was measured using the classical Kjeldahl digestion method and the total phosphorus (TP) concentration was determined by alkaline digestion followed by molybdate colorimetry  and pH of sediment were measured at a soil to water mass ratio of 1:5 using a surveying instrument  equipped with a calibrated combined glass electrode . SOC wasorimetry .4 and 1 g NaCl were added. Subsequently, the mixture was centrifuged at 5000 rpm for 5 min after shaking for 30 s. The extract (1.8 ml) was mixed with 100 mg primary secondary amine sorbent, 150 mg anhydrous MgSO4 and 30 mg graphitized carbon black. They were shaken vigorously for 30 s and centrifuged at 9000 rpm for 5 min  were measured. Briefly, 10 g of sediment after being centrifuged was extracted by 10 ml acetonitrile. After shaking by hand for 30 s, 7.5 g anhydrous MgSOor 5 min . The fin2.3.® Bacterial DNA Kit for Soil  according to the manufacture’s instruction. The fresh sediment sample was used directly for DNA extraction. Extracted DNA was checked using 2% agarose gels. After quality assessment, DNA was stored at −80°C until further analyses. Metagenomic libraries of ten sediment samples were performed by Illumina HiSeq 2,500 platform. Raw sequence data (40.37 Gb) were generated. Sequences were cleaned and assembled using Seqprep, Sickle, BWA, and SOAPdenovo (Version 1.06), and the length of contigs >500 bp were retained for further bioinformatics analyses. CD-HIT was used to build a non-redundant gene catalog, and MetaGene software was used for ORF prediction. Taxonomic assignment was carried by using BLASTP alignment against the integrated non-redundant (NR) database of the National Center for Biotechnology Information  of NCBI using DIAMOND software (Version 0.8.35). On the other hand, for function analysis, DIAMOND software was adopted to blast Unigenes to KEGG (Kyoto Encyclopedia of Genes and Genomes) database  and positive correlation with EC, SOC, N/P (p < 0.01). In addition, EC had significant negative correlation with pH (p < 0.05) and positive correlation with N/P , Actinobacteria (9.39% ~ 25.96%), Chloroflexi (8.83% ~ 19.45%), Acidobacteria (2.99% ~ 10.01%), Gemmatimonadetes (0.67% ~ 5.97%), unclassified_d__Bacteria (1.55% ~ 2.16%), Bacteroidetes (0.33% ~ 5.09%), Candidatus_Rokubacteria  in pathway of phosphonate degradation and was negatively related N/P in pathway of phosphorus. Sulfur metabolism pathway was mainly composed of 4 reaction modules  were positively correlated with the module M00173.As shown in  and CBB . The abu modules : assimil modules : incompl modules : complet modules . P-cycli4.p < 0.05). And, there is no obvious difference in total phosphorus content. Compared with the highly contaminated situation  of Baiyangdian in 2018 reported in January this year  in methane metabolism and the reductive citrate cycle (M00173) module in carbon fixation were further analyzed  were prevalent in soil ecosystem. K01078 (acid phosphatase) and K03788 (acid phosphatase (class B)) belonging to phosphoesterase were not detected in Baiyangdian sediment metagenome, possibly meaning the absence of phosphoesterase metabolism in microbiota. Gene ppk was reported to be a phylogenetic marker of phosphorus removal communities and was widely used to investigate P removal organisms. In addition, it was closely linked the patterns underlying endogenous P release from sediments (ppk) in Baiyangdian sediment metagenome might be associated with the release of underlying endogenous P. The same change trend in the ten sediment samples was also shown in some genes with relatively high abundance, such as, pstABCS, phnCDE and ugpABCE. It might suggest that the strength of P cycling in Baiyangdian lake. And, high microbial potential for efficient phosphate uptake systems  was also detected in P depleted soil (phnA) might increase TP content by breaking C-P bonds. This interesting conclusion was also found in our previous studies  was the main pathway of methane metabolism and the reductive citrate cycle module  accounted for the highest proportion of C fixation processes.Baiyangdian lake sediment was under weak alkaline conditions. Compared with the highly contaminated situation of Baiyangdian in 2018, TN content have dropped almost 40% and TP content have dropped about 35%, however it was still under eutrophication threat. TN showed a relatively greater impact on bacterial communities than TP. The status of OPPs was at an acceptable level of risk and was not the main source of TP. Proteobacteria was the most main phylum in sediment, and was proved to indispensable contribute to C, N, P, S cycling. At site S4, 3-Hydroxypropionate cycling of C fixation was the strongest while the weakest function of denitrification and complete nitrification of N cycling. Many genera involved in C, N, S, P cycling processes, such as, The data presented in the study are deposited in the NCBI repository, accession number PRJNA908081.BK was responsible for writing manuscript. RX was responsible for writing and correcting manuscript. YH, YW, LZ, and ZW were responsible for measurement of environmental factor. JB, KZ, JA, MJ, and WP were responsible for determining research direction. All authors contributed to the article and approved the submitted version.This study was financially supported by National Natural Science Foundation of China (NSFC) and National Research and Development Agency of Chile(ANID) for the China-Chile Joint Projects on Water Resources Management (grant no. 51961125201 in China and NSFC190012 in Chile), and Fuzhou University Testing Fund (project number: 2022T011).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Results showed that in 989 CAP patients, 22 important variables were identified as risk factors. The sensitivity, specificity, and accuracy of the ANNs model training group were 88.9%, 90.1%, and 89.7%, respectively. When ANNs were used in the test group, their sensitivity, specificity, and accuracy were 85.0%, 87.3%, and 86.5%, respectively; when ANNs were used to predict ARDS, the area under the receiver operating characteristic (ROC) curve was 0.943 ). The nine most important independent variables affecting the ANNs models were lactate dehydrogenase (100%), activated partial thromboplastin time (84.6%), procalcitonin (83.8%), age (77.9%), maximum respiratory rate (76.0%), neutrophil (75.9%), source of admission (68.9%), concentration of total serum kalium (61.3%), and concentration of total serum bilirubin (50.4%) . The ANNs model and the logistic regression models were significantly different in predicting and evaluating ARDS in CAP patients. Thus, the ANNs model has a good predictive value in predicting and evaluating ARDS in CAP patients, and its performance is better than that of the logistic regression model in predicting the incidence of ARDS patients.This study aimed to explore the independent risk factors for community-acquired pneumonia (CAP) complicated with acute respiratory distress syndrome (ARDS) and to predict and evaluate the risk of ARDS in CAP patients based on artificial neural network models (ANNs). We retrospectively analyzed eligible 989 CAP patients (632 men and 357 women) who met the criteria from the comprehensive intensive care unit (ICU) and the respiratory and critical care medicine department of Changzhou Second People's Hospital, Jiangsu Provincial People's Hospital, Nanjing Military Region General Hospital, and Wuxi Fifth People's Hospital between February 2018 and February 2021. The best predictors to model the ANNs were selected from 51 variables measured within 24 h after admission. By using this model, patients were divided into a training group ( Community-acquired pneumonia (CAP) is one of the most common infectious diseases in the world, and the nosocomial mortality of CAP patients is about 13% . The morPrediction of ARDS in CAP patients is mainly based on their clinical symptoms, degree of hypoxia , lung imaging findings, and reliable biomarkers . With thNo risk prediction models have been proposed to predict the clinical ARDS in CAP patients. Therefore, it is particularly important to assess the risk of concurrent ARDS in CAP patients. In this retrospective study, a predictive model was constructed to predict the concurrent ARDS in CAP patients, which may provide information for the prevention of ARDS in CAP patients.This retrospective case-control observational study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the ethics committee of our hospital. This was a retrospective study that was approved by the institutional review board, but patient-specific informed consent was not obtained. This study was approved by the Ethics Committee of Changzhou Second People's Hospital, which is affiliated with Nanjing Medical University (IRB: 2020YLJSE086). Furthermore, all the data were provided only to investigators with privacy protection. All the raw data were collected according to the procedures outlined in the epidemiological guidelines.There were 2,228 CAP patients  randomly included from the comprehensive intensive care unit (ICU) and the respiratory and critical care medicine departments of Changzhou Second People's Hospital, Jiangsu Provincial People's Hospital, Nanjing Military Region General Hospital, and Wuxi Fifth People's Hospital between February 2018 and February 2021.9/L or <4 × 109/L, with or without left nucleus migration. (c) Chest imaging revealed a newly patchy infiltrating shadow, leaf/segment solid contrast, ground-glass opacity, or interstitial changes with or without pleural effusion. A clinical diagnosis was established once it met one of the a, c, and b characteristics, when pulmonary tuberculosis, pulmonary tumors, noninfectious pulmonary interstitial disease, pulmonary edema, atelectasis, pulmonary embolism, pulmonary eosinophil infiltration, or pulmonary vasculitis were excluded. Berlin 2012 diagnostic criteria for adult ARDS [2/FIO2 ≤ 300 mmHg, and positive end-expiratory pressure (PEEP) = 5 cmH2O; moderate: 100 mmHg < PaO2/FIO2 ≤ 200 mmHg, and PEEP = 5 cmH2O; severe severity: PaO2/FIO2 ≤ 100 mmHg, and PEEP = 5 cmH2O. If the altitude was above 1,000 m, the correction factor should be calculated as PaO2/FIO2 = atmospheric pressure/760.Diagnostic criteria for CAP in China  are as f+) level, total serum natrium (Na+) level, total serum magnesium (Mg2+) level, fraction of inspiration O2 (FiO2), potential of hydrogen (pH), oxygen partial pressure (PaO2), partial pressure of carbon dioxide (PaCO2), lactic acid (LAC), glasgow coma scale (GCS) score, nutritional risk score, lung injury score, and acute physiology and chronic health evaluation (APACHE). In addition, the gender, age, and source of admission (emergency department and outpatient department), the patient had the worst examination result within 24 h of admission.According to the 51 clinical risk factors of CAP patients with statistically significant were recorded as follows: age, gender, source of admission , maximum temperature (MT), maximum heart rate (MHR), maximum systolic blood pressure (MSBP), maximum respiratory rate (MRR), urine volume within 24 h, complement C4 (C4), hypertension, diabetes, c-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYM), eosinophil count (EO), fibrinogen equivalent unit (FEU), fibrinogen (FBG), activated partial thromboplastin time (APTT), alkaline phosphatase (ALP), albumin (ALB), total protein (TP), total bilirubin (TBIL), prealbumin (PA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase(LDH), creatine kinase isoenzyme (CK-MB), troponin I (TNI), B-type natriuretic peptide (BNP), creatinine (CREA), blood urea nitrogen (BUN), uric acid (UA), red blood cell count (RBC), hemoglobin (HGB), platelet (PLT), glucose (GLU), total serum kalium . Exclusion criteria were as follows: (1) There was confirmed severe respiratory dysfunction before the onset of CAP, such as acute respiratory distress syndrome, acute respiratory failure, severe pulmonary edema, and acute exacerbation phase of chronic obstructive pulmonary disease; (2) patients were admitted to hospital for pneumonia more than 2 times or patients required long-term oxygen therapy after tracheostomy; (3) the patient was transferred from other departments to the general ICU or the Department of Respiratory and Critical Care Medicine during the hospitalization; (4) presence of hospital-acquired pneumonia during hospitalization; (5) cardiac pulmonary edema during hospitalization; (6) presence of other risk factors on admission, cancer, heart failure or kidney failure, blood disease, and tuberculosis; (7) the disease condition was stable or normal within 48 h after admission; (8) patients with >30% deletions in the clinical risk variables; (9) patients with missing data in the identified clinical variables; (10) hospital stay <24 h; (11) incomplete clinical information.Xi is used as the input neurons; the dependent variable Yj  is the output neurons, and the output layer is ARDS ; its transfer parameters are expressed by the activation function identity. ANNs were conducted based on the building block of the single implicit layer with the classes separated through the following equation:x represents the input, w_i represents the weights, b represents the bias, and y represents the output.The 3-layer network model, including an input layer, output layer, and hidden layer, is mainly used to analyze the data. The independent variable K as the number of hidden layers, all data are normalized by K is determined as 1 hidden layer including five neuronal units. As synaptic weights, its transfer function is dominated by the hyperbolic tangent function and reported by the activation function tangent curve. All the data were divided into a training dataset and a validation dataset at 7 : 3 ratio. The training dataset is used for network learning to build the prediction model, and the validation dataset is used to evaluate the performance of the model.With The logistic regression (LR) model is a generalized linear regression model, similar to the ANN model. In this model, the dependent variables serve as the output one, which is a binary variable . The independent variables are the clinical risk factors as initial input ones, such as age, sex, heart rate, and hypertension. Independent variables can be continuous or categorical variables. In the logistic regression analysis, the weight of each independent variable can be obtained, and the risk factors for developing ARDS are determined. Meanwhile, the weight can be used to predict the likelihood of developing ARDS in a specific person based on the risk factors. The combination of each predictor was employed to predict the ARDS by a link function, logistic. The dataset was randomly divided into training and validation groups at a 1 : 1 ratio and the dataset in the training group was used to construct the LR model.X ± SD), and compared with an independent sample t-test between two groups. Data without normal distribution are expressed as medians (P25–P75), and compared with a nonparametric Kruskal–Wallis rank-sum test between the groups. Categorial data are expressed by frequency and rate, and compared between groups by the chi-square test. A value of P < 0.05 was considered statistically significant. ANN analysis was performed using SPSS Clementine11.1. The LR and ANN models were established to predict the risk of developing ARDS in CAP patients. Predictive performance was evaluated by sensitivity (SEN) and specificity (SPE). Dichotomous variables were created from continuous variables according to clinically important cut-off values.  was used to delineate the receiver operating characteristic (ROC) curves, and the area under the ROC curve (AUC) was calculated.All data were analyzed using SPSS version 26.0 statistical software. Data with normal distribution are expressed as mean ± standard deviation  with a mean age of 68.48 ± 29.49 years were diagnosed with CAP alone, and 323 (32.7%) CAP patients developed ARDS . AccordiX1–X19, including the dependent variables X1–X4, gender X1, admission source X2, hypertension X3, and diabetes X4. Covariates X1–X19 were entered sequentially, including age X1, heart rate X2, MRR X3, CRP X4, PCT X5, ESR X6, NEUT X7, EO X8, FEU X9, APTT X10, TBIL X11, ALB X12, LDH X13, CREA X14, HGB X15, GLU X16, PLT X17, K+X18, and Na + X19. The output layer was ARDS . The number of hidden layers as interneurons was set as 5. The topological stratification structure of the neural network model is plotted , APTT (84.6%), PCT (83.8%), age (77.9%), MRR (76.0%), NEUT (75.9%), admission source (68.9%), K+(61.3%), and TBIL (50.4%)   .P < 0.05). Age, gender, MHR, MRR, admission source , hypertension, CRP, PCT, ESR, NEUT, EO, FEU, APTT, TBIL, ALB, LDH, CREA, HGB, PLT, GLU, K+, and Na+ were included into the multivariate LR analysis as predictive variables. The final LR equation was logit (P) = −2.745 + 3.948 × admission source + 0.004 × CRP + 0.045 × PCT + 0.008 × ESR − 0.009 × NEUT − 0.47 × ALB + 0.03 × LDH, and P represents the predicting probability of the LR model . The AUC was calculated in the LR and ANN models established using the validation dataset and used to identify the ARDS. The AUC of the ANN model was 0.943 (95% CI: 0.918–0.968), and the AUC of the LR model was 0.942 (95% CI: 0.923–0.961)  .CAP developed severe CAP and needs intensive care patients, the most common complication is ARDS. ARDS is a heterogeneous syndrome, including direct and indirect causes of lung injury, and pulmonary ARDS is a CAP sepsis-like inflammatory reaction and alveolar endothelial injury . Some st+, and TBIL played important roles in predicting the occurrence of ARDS in CAP patients, and some previous studies have investigated the specific risk factors of ARDS in CAP patients. As a key enzyme in the glycolytic pathway, LDH is a cytoplasmic enzyme in most organs, which is associated with an inflammatory response and cellular damage. Zhou et al. found that bacterial or viral mRNA clearance is highly correlated with LDH level, and CAP patients infected by bacteria or viruses may have inflammasome activation, induction of apoptosis, and invasive symptoms, which can partly explain the association of LDH with CAP and ARDS [This study for the first time investigates the predictive model of ARDS in CAP patients with conventional variables. In this model, all objective and commonly used clinical variables collected within 24 h after admission were included. The predictive model of ARDS in CAP patients constructed with the ANN model has good predictive and calibration power. In our study, LDH, APTT, PCT, age, MRR, NEUT, admission source, Kand ARDS . Zhou etand ARDS . Pathophand ARDS . CAP patand ARDS , and theand ARDS . It has and ARDS . Tang etand ARDS . The immand ARDS , which iand ARDS . The souand ARDS , 26. Fu and ARDS . Our resand ARDS . These mand ARDS , which wand ARDS , 31, whiP > 0.05). ANN was used in this study. Compared with the traditional LR, ANN is a nonlinear mathematical model, and its unique working principle has almost no restrictions on the characteristics of data used for analysis, which helps fit complex multifactorial diseases and has good sensitivity and specificity [CAP patients have a high risk for ARDS. In the present study, a predictive model was established to predict ARDS in CAP patients. The previous pre-established ARDS model based on different risk factors on admission has a good predictive ability and focuses on the prediction of ARDS in CAP patients. The clinical outcomes and biomarker characteristics of CAP patients with ARDS differ from patients with ARDS unrelated to non-CAP risk factors, which reflects the unique potential clinical factors and the special pathogenic mechanism of CAP . In the cificity . TherefoThere were still limitations in this study: First, the sample size was small in patients with ARDS, and thus more clinical studies with a large sample size are needed to improve the accuracy of the prediction model and confirm our study. Second, some predictors have been repeatedly mentioned in the studies, such as smoking, body mass index, acute physiology, and chronic health evaluation II, complement C3, but they were not included as potential predictors in this study. Third, there was an overlap between some predictors in this study . However, the aim of this study was not to establish an independent association between risk factors and ARDS. Instead, our study aimed to determine the combination of variables that can achieve the best predictive performance for CAP-related ARDS. Fourth, the case size in the present study was not very well established, due to the heterogeneity in the ARDS heterogenicity, compromising the identification ability of these predictors. Fifth, early lack of CAP patients with a conclusion urea respiratory rate and age 65 (CURB-65) for grouping, To further predict the high-risk group (CURB-65 score 3 points) model. Sixth, causal inference is an important aspect of machine learning , but theIn conclusion, the predictive model constructed in this study based on the ANN model using the indicators collected early after admission can be used to calculate and stratify ARDS in CAP patients. Specifically, the model can be used to calculate risk and intervene in the early targeting of meaningful markers in this study. The model may provide a reference for the early allocation of medical resources and help to guide the clinical management of CAP patients.