Handgrip strength (HS) is a risk factor of all-cause mortality and cardiovascular diseases. However, the influencing factors and mechanisms contributing to this correlation remain unclear. Therefore, we aimed to explore factors related to HS and investigated the mechanism underlying its risk predictive value. BMI) and body surface area (HSBSA). Body composition was assessed via bioimpedance spectroscopy. Physical fitness was measured using a cardiopulmonary exercise test system. Univariate, multiple linear regression analyses and receiver operator characteristic curve (ROC) were conducted to evaluate the associations between various participant characteristics and HS.  This was a prospective, cross-sectional study. One hundred forty-five participants were recruited from December 2019 to November 2020. HS was measured using a hydraulic hand dynamometer and adjusted for body mass index . Lean-tissue, protein, total water, and inorganic salt percentages were positively correlated, and fat percentage was negatively correlated with HSBMI in men and with HSBMI and HSBSA in women (p < 0.05). Multiple regression revealed that VO2max was independently associated with HSBSA in both sexes  and independently associated with HSBMI in women . ROC analysis showed that HSBMI and HSBSA can moderately identify normal VO2max in men  and marginally identify normal VO2max in women .  The average participant age was 21.68 ± 2.61 years . We found positive correlations between HSBSA may moderately reflect cardiorespiratory fitness levels in healthy young adults, particularly in males. Clinical trials registry site and number: China Clinical Trial Center (ChiCTR1900028228). BMI- and BSA-adjusted HS could serve as indicators of physical health, and HS Handgrip strength (HS) is a simple measurement and a useful indicator of physical strength. HS has been found to be strongly correlated with maximum upper and lower body strength and overall muscle strength . TherefoBMI/HSBSA) has been used to reduce the influence of heterogeneity on the results [Previous studies have shown that HS depends on age, sex, body size, socioeconomic status, and physical activity levels , 11; mal results .2max, a representation of cardiorespiratory fitness (CRF), is closely correlated to physical health. Low VO2max is recognized as a strong and independent risk factor for all-cause mortality, CVD [2max was consistent with HS affecting health outcomes in healthy population [2max in paraplegic men [VOity, CVD , diabeteity, CVD , and neoity, CVD  in healtpulation , 18. A regic men . TherefoChiCTR1900028228).This was a prospective, cross-sectional study. This study is part of the “Study for the application value of grip strength on the unaffected side in patients with stroke”, which involves two steps. The first step is to explore the correlation between HS and CRF in healthy young adults, the aim of the current study. The next step is to test whether the association between grip strength and cardiorespiratory fitness persists in stroke patients, which will be undertaken in the future. Our overall goal is to extrapolate the associations found in healthy young adults to stroke patients and to provide a useful predictive tool for stroke patients who have difficulty undertaking cardiopulmonary exercise tests. In the current study, the data were obtained from the rehabilitation center of Shenzhen Second People's Hospital and Shenzhen Dapeng New District Nan'ao People's Hospital, Shenzhen City, China. This study conforms to the standards of the Declaration of Helsinki, was approved by the Ethics Committee of Shenzhen Second People's Hospital (KS20191119005), and was registered at the China Clinical Trial Center (https://www.danielsoper.com), a minimum sample size of 70 participants of each sex was needed to achieve 90% power and to detect an effect size (Cohen's f2) of 0.26 attributable to 5 independent variables using an F-Test  with a significance level  of 0.05. Combined with a 10% shedding rate, 154 subjects were needed for this study. The participants were recruited from December 2019 to November 2020 based on the following inclusion and exclusion criteria. The inclusion criterion was healthy young adults (aged 18–24 years) with a stable physical condition. The exclusion criteria were (1) congenital heart disease, (2) history of cardiac arrest, (3) neurological or muscular disorders, (4) fever or infection, and (5) allergy to electrode pads. Before data collection, participants were informed of the objectives and methodology of the study, and written informed consent was obtained. Tea or coffee was prohibited for at least 3 h before the tests. Tests were performed in an evaluation room with a temperature of 22–25°C. Except for scientific purposes, personal information and experimental data were kept strictly confidential.Study participants were recruited using a convenience sample of young adult interns in the hospital. Based on the sample size calculation method for a multiple regression study (2), body surface area (BSA), and resting heart rate ; (3) body composition, including lean-tissue percentage (%), fat percentage (%), protein percentage (%), total water percentage (%), and inorganic salt percentage (%); (4) physical fitness, including AT (ml/kg·min), VO2max (ml/kg·min), HRrest (rpm), HRAT (rpm), HRmax (rpm), RERmax, VEmax (ml/min), Loadmax (W), Psysmax (mmHg), Pdiamax (mmHg), METmax, ΔVO2/ΔLoad, ventilatory equivalent for carbon dioxide (VE/VCO2), and oxygen uptake efficiency slope (OUES); and (5) living habits, such as smoking status (current smoker or nonsmoker) and exercise habits . BMI was calculated as body weight/height in meters squared (kg/m2). BSA was calculated using Mosteller formula [rest was calculated as the average heart rate during 10 min of quiet sitting. Body compositions were measured using a body bioimpedance spectroscopy . Physical fitness was measured via a cardiopulmonary exercise test (CPET) evaluation system .Data for the following parameters were recorded within 72 hours after admission (baseline): (1) demographic factors, such as sex and age (years); (2) anthropometric factors, such as height (m), weight (kg), body mass index , and the mean of the right- and left-side values was recorded as the average HS (HSaverage). HS is partly associated with body size [average for BMI and BSA and created two new indicators, HSBMI and HSBSA, respectively.HS was measured using a hydraulic hand dynamometer . Based on previous authoritative research , the staody size ; therefo2max) [In accordance with the “Clinician's Guide to Cardiopulmonary Exercise Testing in Adults: A Scientific Statement from the American Heart Association” , the gra2max) . Gas exc2max (ml/kg·min). According to previous studies [2max < 30 ml/kg · min is defined as abnormal, and VO2max ≥ 30 ml/kg · min is normal. In female young adults, VO2max < 25 ml/kg · min is regarded as abnormal, and VO2max ≥ 25 ml/kg · min is normal. The anaerobic threshold (AT) was determined by the V-slope and ventilatory equivalents methods [2 from a line of identity drawn through a plot of VCO2 versus VO2 in the V-slope method, as well as the point at which a systematic increase in the ventilatory equivalent for oxygen (VE/VO2) occurs without an increase in the VE/VCO2 in the ventilatory equivalent method [a log10VE + b (a as OUES), which can reflect the linear relationship between logarithmically transformed VE and VO2 [Oxygen uptake at maximum load was recorded for each participant as VO studies , in malet method . The res2max) were excluded from the final analysis. Secondary indicators that were partially missing were filled in with a mean value. The correlation between HSBMI and HSBSA and other characteristics were analyzed by Pearson or Spearman analysis. Multivariate linear regression analysis was conducted to explore factors independently correlated with HSBMI and HSBSA. To avoid potential multicollinearity, once a variable had been used to adjust for other variables, it was not included as a covariate in the multivariate linear regression analysis. The receiver operating characteristic curve (ROC) was used to investigate the relationship between sensitivity and specificity. The optimal cutoff scores of HSBMI and HSBSA were determined as the score with the highest sum of sensitivity and specificity. The area under the curve (AUC) was calculated to identify the discrimination potential of HSBMI and HSBSA cutoff score in normal VO2max. Because male and female young adults differ substantially in terms of muscular fitness and CRF, statistical analyses were performed separately to analyze the different variables related to HSBMI/HSBSA in the two sexes. Analyses were performed using SPSS version 21.0 . Figures were processed using GraphPad Prism version 6.01 . Two-sided p values < 0.05 were considered statistically significant.Continuous variables with a normal distribution are expressed as mean ± standard deviation (SD). Categorical variables are expressed as frequency or percentage. The sample size was calculated based on the recorded numbers and reference to an earlier study . Particin = 2), arrhythmia (n = 1), refusal (n = 3), and missing important data (n = 5), 145  healthy, Chinese young adults (average age 21.68 ± 2.61 years) were included for the final data analysis. Basic and anthropometric-related characteristics of the included participants are summarized in left, HSright, and HSaverage), body composition-related factors  and CRF-related factors  in males were much higher than those in females (p < 0.05). Conversely, the fat percentage and resting heart rate in males were much lower than those in females (p < 0.05), indicating that muscular fitness, body composition, and CRF were much different between male and female young adults in this study. Therefore, it was necessary to analyze male and female participant data separately.The study flowchart is shown in 2max, VEmax, Loadmax, and METmax) were all significantly correlated with HSBMI and HSBSA (p < 0.05). In young female adults, body composition, including lean-tissue percentage, fat percentage, protein percentage, total water percentage, and inorganic salt percentage, were all significantly correlated with HSBMI (p < 0.05). Furthermore, CRF-related factors  were all significantly correlated with HSBMI and HSBSA (p < 0.05). These results reflected that HSBMI and HSBSA were associated with various health-related indicators and had the potential to reflect overall health conditions.The results of the correlation analysis are presented in BMI, HSBSA with anthropometric variables, and CRF-related variables. Based on the results of the univariate correlation analysis, having excluded factors of collinearity, the dominant factors correlated with HSBMI and HSBSA were selected into the multivariate linear regression. As shown in BMI independently , and VO2max was positively associated with HSBSA independently . In females, VO2max was positively associated with both HSBMI and HSBSA independently .Multivariate linear regression analysis was performed to analyze the independent association among HSBMI explained 20.7% of the variance of VO2max , and HSBSA explained 21.4% of the variance of VO2max . While in female participants, HSBMI explained 5.9% of the variance of VO2max , and HSBSA explained 7.1% of the variance of VO2max .The results of the linear regression analysis are presented in BMI and HSBSA used to distinguish a normal level of VO2max were 2.17 and 33.83 , with an area under the curve (AUC) of 0.754 and 0.769 . In female participants, the optimal cutoffs in HSBMI and HSBSA used to distinguish a normal level of VO2max were 1.17 and 15.86 , with an AUC of 0.643 and 0.635 .The results of ROC analysis are presented in BMI and HSBSA. Multivariate regression analysis revealed that VO2max was independently associated with HSBSA in both male and female young adults. These findings confirm HS as an indicator of physical health and reveal the possible mechanism underlying the risk predictive value of HS.In this study, we explored factors associated with HS to identify potential mechanisms underlying health outcomes in healthy young adults. Our results indicated that several types of health-related factors, including body composition, physical fitness, and CRF, were correlated with HSHS is affected by many demographic factors, such as age, sex, and BMI. The highest HS scores typically occur between the ages of 24 and 39 years. During normal aging, HS will decrease due to changes in anabolic resistance and reduced physical activity participation . RiviatiBMI and HSBSA. Our findings are consistent with an earlier study, in which HS was positively correlated with lean tissue mass, lean tissue index, and serum albumin level in hemodialysis patients [BMI and HSBSA; therefore, these associations may explain why a low level of HS is correlated with high cardiovascular risk [2max, indicating that the relationship between HS and CRF was more stable than that between HS and other factors.Anthropometric indicators also influence HS. In the current study, lean-tissue percentage, protein percentage, total water percentage, and inorganic salt percentage were positively correlated with HSpatients . The pospatients . Converspatients . In thislar risk . FurtherR = 0.549, p ≤ 0.001) [2max with nonexercise factors in frail populations in the future [Previous studies have indicated a close association between HS and cardiovascular health and cardiac structure and function –35. Beye≤ 0.001) , which ie future , 41.The mechanism underlying the association between HS and CRF remains unclear. As reported in the literature, pyruvate dehydrogenase (PDH) might be one of the links. Love et al. found that PDH phosphatase activity is associated with muscle aerobic capacity . Muscle BMI/HSBSA and CRF was strong in young male adults but weak in young female adults. This may be because HS is strongly influenced by the heritability of sexually dimorphic traits [2max level is the result of the combined effect of muscle strength and heart and lung function during extreme exercise, and because HS is strongly associated with overall muscle strength [An interesting finding of this study was that the association between HSc traits , rangingc traits . Anotherc traits . Similarstrength , the dom2max may partly explain why HS is a risk factor of all-cause mortality and cardiovascular diseases. Second, the results provide evidence to support muscle strength training as a means to improve CRF. Third, HS, as a simple evaluation index, can moderately reflect the level of CRF and accordingly may act as a potential predictor of CRF levels in frail populations or communities where cardiopulmonary exercise testing is not possible.The clinical significance of this study lies in the following. First, the close relationship between BMI- and BSA-adjusted HS and VOThere are some limitations to the present study. First, our research subjects were young healthy Chinese adults within a narrow age range limiting generalization to other populations. In future studies, subjects from different age groups should be included. Moreover, we excluded participants with congenital heart disease, a history of cardiac arrest, and muscular disorders. Therefore, the findings of this study cannot be generalized to people with these conditions. Finally, our sample size was small. Future studies with larger sample sizes are necessary to ensure generalizability of the findings.BMI and HSBSA were correlated with various health-related indicators, including body composition factors  and CRF factors . HSBSA was independently associated with VO2max levels, especially in males. These associations may partly explain why HS is correlated with health risks. Therefore, we suggest that HSBMI and HSBSA could serve as indicators of physical health, and HSBSA could be used to partially reflect CRF levels in healthy young adults. Larger studies are required to strengthen our conclusions and explore the application value of HS in varied populations.Our results showed that HS


Fecal calprotectin (FC) is a non-invasive biomarker used in inflammatory bowel disease (IBD) management and risk stratification of non-specific gastrointestinal symptoms. Leukocyte esterase is an inexpensive and widely available point-of-care inflammatory marker present on urinalysis test strips.We aim to assess the diagnostic accuracy of fecal leukocyte esterase (FLE) relative to FC and endoscopy and demonstrate its use as an alternative biomarker for IBD.In this prospective cohort study, 70 patients who had FC ordered as part of standard clinical care also received FLE testing. FLE levels were compared to various FC cut-off values, endoscopy and pathology findings as gold standard.As the FC cut-off increased from 50 to 500 μg/g, FLE sensitivity increased from 67% to 95% while the specificity decreased from 86% to 76%. The area under the receiver operating characteristic (AUROC) increased from 0.79 to 0.90. An FLE of ≥1+ had the best test characteristics. Amongst patients who underwent endoscopic evaluation, FLE demonstrated an identical sensitivity (75%) and specificity (86%) to FC in predicting endoscopic inflammation. AUROC was 0.80 for FLE and 0.85 for FC with an optimal cut-off of ≥2+ and 301 μg/g, respectively. When used to distinguish between active IBD and no/inactive IBD patients, FLE had a sensitivity of 84% and specificity of 90%, comparable to the 84% and 83%, respectively, of FC. AUROC was 0.88 for FLE and 0.91 for FC with an optimal cut-off of ≥2+ and 145 μg/g, respectivelyFLE demonstrates adequate correlation and comparable accuracy to FC in predicting endoscopic inflammation and distinguishing between patients with active versus inactive IBD.None


In addition, hepatic mRNA sequencing further indicated that the HJZ group can regulate the peroxisome proliferator-activated receptor (PPAR) pathway and inflammatory signaling pathway, as validated by RT-PCR and Western blot. We also found that different doses of JZG may regulate lipid metabolism through differentiated pathways, as LJZ mainly through the promotion of hepatic lipid hydrolysis, while HJZ mainly through the improvement of hepatic lipid oxidation. Taken together, JZG could modulate gut dysbiosis with dose-effect, alleviate inflammation level, and regulate hepatic lipid metabolism, which may subsequently contribute to the improvement of NAFLD. Our study revealed the underlying mechanisms in the improvement of NAFLD by a Chinese herbal compound, providing future guidance for clinical usage.Recently, accumulating evidence revealed that nonalcoholic fatty liver disease (NAFLD) is highly associated with the dysbiosis of gut microbiota. Jiang Zhi Granule (JZG), which is composed of five widely used Chinese herbs, has shown hypolipidemic effect, while whether such effect is mediated by gut microbiota is still unclear. Here, we found that both low and high doses of JZG (LJZ and HJZ) could improve hepatic steatosis and function, as well as insulin resistance in NAFLD mice. 16S rRNA gene sequencing revealed that JZG treatment could reverse the dysbiosis of intestinal flora in NAFLD mice, exhibiting a dose-dependent effect. Notably, HJZ could significantly reduce the relative abundance of Desulfovibrionaceae, while increasing the relative abundance of such as S24_7 and Lachnospiraceae. PICRUSt analysis showed that HJZ could significantly alter the functional profile of gut microbiota, including the reduction of the lipopolysaccharide biosynthesis and sulfur metabolism pathway, which is verified by the decreased levels of fecal hydrogen sulfide (H NAFLD is one of the most common chronic liver diseases worldwide, and its incidence is rising rapidly –4. NAFLDThe gut microbiota is the largest microbial community in the human body, playing important roles in the host homeostasis . StudiesMany herbal remedies and their active components used in traditional Chinese medicine (TCM) have shown overt anti-obesity and anti-NAFLD effects, while gut microbiota has been implied as one of the important targets –27. JianGynostemma pentaphyllum (Thunb.) Makino (15 g), Polygoni cuspidati rhizome (15 g), Folium nelumbinis (6 g), Artemisia capillaris Thunb (9 g), and Salviae miltiorrhizae Radix (9 g). JZG was administered at the low  and high  doses in mice, according to the clinical equivalent dose [JZG was purchased from Sichuan Neo-Green Pharmaceutical Technology Development Co., Ltd., composed of ent dose . In prevent dose .6 to 8-week-old male C57BL/6 mice were purchased from Shanghai Research Center of Southern Model Organisms  and maintained in specific pathogen-free (SPF) environments. All animal experiments in this study were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine and conducted under the “Guide for the Care and Use of Laboratory Animals” recommended by the US National Institutes of Health.n = 10) and (2) high-fat diet  group . After 16 weeks of HFD diet, the NAFLD mouse model was evaluated to be successfully established by dissection of two mice in each group. Then, the HFD group was randomly divided into three groups of 8 mice each: (1) HFD group, fed a HFD and administered by 0.5% sodium carboxymethyl cellulose intragastrically once daily; (2) LJZ group, fed a HFD and administered LJZ intragastrically once daily; and (3) HJZ group, fed a HFD and administered HJZ intragastrically once daily. After 8-week administration, all animals were sacrificed under anesthesia, and the blood, liver, and intestinal tissues were harvested following refined protocols.After one week of acclimatization, mice were randomly assigned to two groups fed different chows: (1) normal chow diet group  and aspartate aminotransferase (AST) were determined using Catalyst One Chemistry Analyzer. Total triglyceride (TG), total cholesterol (TC), free fatty acids (FFAs), superoxide dismutase (SOD), and malondialdehyde (MDA) in extracted hepatic samples were measured with corresponding assay kits . Serum insulin and LPS-binding protein (LBP) were determined using ELISA kits  according to the manufacturer's instructions.The liver tissues of mice were isolated and fixed in 10% formalin solution for 48 h. The tissues were dehydrated, cleared, waxed, embedded, sliced, and stained with hematoxylin and eosin (H&E). The presence of steatosis was further confirmed using Oil Red O staining of frozen liver sections. The morphological differences of the tissues were examined under a light microscope, and all quantitation was performed in Image-Pro Plus software 6.0.To determine the structure and function profile of gut microbial community, we used Illumina high-throughput sequencing to sequence the 16S rRNA gene V3-V4 region of the gut microbiota in mouse feces. Total bacterial DNA was extracted from mice fecal samples using the DNeasy PowerSoil Kit . Amplicon library for double-ended (2 × 300 bp) sequencing was constructed using the forward primer 338F (5′-ACTCCTACGGGAGGCAGCA-3′) and the reverse primer 806R (5′GGACTACHVGGGTWTCTAAT-3′) on Illumina MiSeq platform. PCR amplicons were purified with Agencourt AMPure Beads  and quantified using the PicoGreen dsDNA Assay Kit . After quantification, amplicons were pooled in equal amounts. The raw reads were quality-filtered and merged . Paired-2O and then 0.01 mL of 50% H2SO4 and 1 mL of diethyl ether. After vortexing for 30 s, the mixture was centrifuged at 4°C and 10000 rpm for another 5 min. 200 μL of the supernatant was acquired and then measured by GC on an Agilent7000B system  equipped with flame ionization, thermal conductivity detectors, capillary columns, and GC ChemStation software. Acetate, butyrate, propionate, valerate, isobutyrate, and isovalerate were quantified using pure standards diluted in diethyl ether.Cecal SCFA concentration was measured by gas chromatography/mass spectrometry (GC/MS). Briefly, 50 mg of cecal content was homogenized with 0.8 mL ddHμL phosphate buffer (pH 7.2). The fecal supernatant was mixed thoroughly before centrifugation at 16000 rpm for 15 min at 4°C. The supernatant was collected and centrifuged again for 10 min. 100 μL of the supernatant was acquired and then was homogenized with 100 μL phosphate buffer solution and 10 μL of Sulphide I reagent . After standing for 5 s, 10 μL of Sulfide II reagent  was added into the mixture. After standing another 5 min at room temperature, the absorbance of the mixture was determined at a wavelength of 665 nm by a Hach DR 5000 spectrophotometer  [The fecal supernatant was prepared according to the ratio of 1 mg feces compared to 2 Germany) .n = 3) which were randomly selected. An RNA Seq library was constructed using Illumina TruSeq RNA Sample Preparation Kit, according to the manufacturer's instructions. We then used the PCR amplification to enrich the library fragments as long as 300-400 bp. Then, the Agilent 2100 Bioanalyzer was used for quality inspection of the library. Then, next-generation sequencing technology  was used to perform paired-end sequencing of these libraries based on the Illumina HiSeq sequencing platform . Then, we use HTSeq to compare the Read Count value of each gene as the original expression of the gene and use FPKM to normalize the expression.Total RNA was extracted from the livers of the NCD, HFD, and HJZ groups  . RT-PCR was performed on a LightCycler96  using iQ SYBR Green Supermix . The relative expression of lipid synthesis-related genes Scd1, PPARγ ), lipid γ ), lipid γ , PPARα [γ [α ), lipid γ [α ), intestγ [α ), and inγ [α , TLR2, Tγ [α ) were ad, PPARγ ,α , Fabp5 , and CD14 .Mouse liver tissues were lysed in RIPA buffer with 1× protease and phosphatase inhibitor cocktail to extract total protein. The total protein concentration in the supernatant was determined using the BCA method. After samples were denatured at 100°C for 5 min, equal amounts of proteins were run on a 10% SDS-PAGE gel and then transferred onto a PVDF membrane. Membrane was blocked with 5% nonfat milk in 0.1% TBST for 2 h at room temperature and then incubated with a primary antibody overnight at 4°C. After extensive washing, the membranes were incubated with the appropriate HRP-conjugated secondary antibody at room temperature for 2 h. Finally, the blots were developed with an ECL reagent. The following primary antibodies were used: GAPDH , YM3029, 1 : 5000), PPARα and intestinal Occludin expression were evaluated using paraffin-embedded liver and ileum tissues, respectively. After deparaffinization, the slides were heated in an autoclave with sodium citrate for antigen repairing, followed by 1% hydrogen peroxide to abolish endogenous peroxidase activity, and blocked with 2% goat serum. Slides were then incubated with primary antibodies including PPARα  and Occludin  at 4°C overnight. HRP-conjugated secondary antibodies (1 : 200) were incubated for 50 min at room temperature. After PBS washing, peroxidase substrate DAB  was used for color development.The hepatic PPARU test; multiple group comparisons were made by the Kruskal-Wallis test or one-way ANOVA, using GraphPad Prism 8.4 software. p < 0.05 was considered statistically significant. Other statistical analyses were described in the corresponding figure legends.Data were presented as the means ± standard deviation. Graphs are depicted as violin plots to display the distribution of the data. Statistical differences in the biochemical index and the distance of the gut microbiota between groups were assessed by the Mann–Whitney After the establishment of NAFLD model by 16 weeks HFD, different doses of JZG were administered intragastrically for 8 weeks to investigate the therapeutic mechanism of JZG. As shown in Furthermore, biochemical parameters in the serum and liver revealed that hepatic TC and TG levels were significantly increased in the HFD group compared to the NCD group and were significantly decreased in the LJZ and HJZ groups compared to the HFD group Figures . Serum ip = 0.08; HJZ vs. HFD: p = 0.059) (p < 0.05) and increased diversity in the HJZ group compared to the HFD group (p < 0.05)  . At fami= 0.059) , JZG, es < 0.05) . Beyond g groups . The gutg groups .To further identify the key bacteria, we performed differential analysis based on the random forest analysis and Wilcoxon rank-sum test. In all, 20 families were identified as the discriminative families among four groups through random forest analysis, and Ruminococcaceae, Paraprevotellaceae, and Desulfovibrionaceae were ranked as the highest discriminative families . All theChanges in the structure and symbiotic relationship of gut microbiota also indicate functional changes. We then performed PICRUSt analysis to predict the function of the gut microbiota. The PCoA analysis of all the bacterial functions based on Bray-Curtis distances revealed that HFD could change the functional profile of the gut microbiota while the HJZ could alter the changes resembling to that in the NCD group . 23 KEGG2S and plasma concentration of LBP induced by HFD  , while there was no difference between the HFD group and JZG group , while bacteria enriched in the NCD and JZG group such as S24_7, Lachnospiraceae, and Bifidobacteriaceae were negatively correlated with NAFLD-associated metabolic parameters.Bacteria-associated metabolites were further detected to verify the results of PICRUSt. HJZ could significantly reduce the increase of fecal concentration of H Figures . The totZG group . The corZG group . We founWe then performed hepatic mRNA sequencing to analyze the metabolic changes on transcriptome level during JZG treatment. We found that compared with the NCD group, the expression of 479 genes was significantly upregulated and that of 459 genes was significantly downregulated by HFD. Meanwhile, compared with the HFD group, the expression of 58 genes was significantly upregulated and that of 57 genes was significantly downregulated by the HJZ group , lipid hydrolysis-related genes , lipid oxidation-related genes , and lipid transport gene (Fabp5) in liver tissues was measured by RT-PCR. The results showed that, compared with the HFD group, the LJZ group significantly upregulated the expression of genes involved in lipid hydrolysis (α genes in the livers of LJZ and HJZ groups was verified by Western blot and immunohistochemistry (Figures RT-PCR analysis was preformed to verify the transcriptome results on lipid metabolism and inflammatory signaling pathways. The expression of lipid synthesis-related genes (Scd1 and PPARdrolysis  and the drolysis ; both thdrolysis . The hig Figures . Meanwhi Figures . Otherwi Figures , indicat Figures .Many natural herbs have been reported to be effective in the treatment of metabolic diseases, while intestinal microbiota is highly supposed as one of the pivotal targets. In this study, we found that JZG, a Chinese herbal compound prescription, could improve hepatic steatosis and liver function in a NAFLD mouse model and further investigated the effects of JZG targeted at intestinal microbiota through multiomics approach. Our results showed that different doses of JZG could not only ameliorate gut dysbiosis in NAFLD mice with a dose-effect but also improve liver steatosis through differentiated regulatory pathways of lipid metabolism, as LJZ through the promotion of hepatic lipid hydrolysis, while HJZ through the improvement of hepatic lipid oxidation.2S, a toxic gas for colonic epithelial cells [2S and the LBP in the HJZ group [Desulfovibrio vulgaris from Desulfovibrionaceae also showed anti-NAFLD effects [The present study showed that different doses of JZG have dose-dependent effect on intestinal microflora. Both doses of JZG could change the gut flora, while the structure and function of gut microbiota in the HJZ group were much more resembling to that in the NCD group, while diverging to that in the HFD group. Our finding is consistent with a previous intervention study that found higher doses of berberine and metformin played a better role in gut microbiota regulation . Notablyal cells , 47. Moral cells –52. As fJZ group . Interes effects , which h effects . Lachnos effects  which co effects . We founGynostemma pentaphyllum, one vital ingredient of JZG, also could enrich beneficial intestinal bacteria and modulate inflammatory intestinal microenvironment [Akkermansia muciniphila [As a consequence of the improved dysbiosis of gut microbiota, we also found that JZG could improve the intestinal barrier function, the intestinal and hepatic inflammation levels, insulin resistance, and hepatic lipid accumulation. A previous study has reported that extraction from ironment . Anotheriniphila . Our resiniphila  and induiniphila . TLR2 exiniphila , 62. JZGα and Fabp5 on both RNA and protein levels. PPARα is the master regulator of lipid metabolism in the liver by regulating the expression of genes involved in fatty acid uptake and intracellular trafficking, lipid deposition, and, mostly, β-oxidation [Finally, our study revealed the underlying mechanisms of the regulation of hepatic lipid metabolism by JZG with dose effect. Transcriptome results showed that the HFD group can inhibit fatty acid degradation and PPAR signaling pathways, while the HJZ group could reverse the obesogenic effects. Our results found that the HJZ group mainly increased the expression of genes related with fatty acid oxidation, while the LJZ group mainly increased the expression of genes related with lipolysis. A previous study of Flavokawain A also found a dose-effect of anti-inflammatory effects . Anotherxidation . Fabp5 rxidation , 67. TheIn conclusion, our study suggested that JZG could modulate bacterial composition and function with dose-effect, improve gut permeability, alleviate intestinal and hepatic inflammation level, and regulate liver lipid metabolism and then may subsequently ameliorate NAFLD. Our study shed light on further investigation of the clinical utility of Chinese herbal compound, which has been understudied in the treatment of NAFLD.


Actinidia arguta) leaf under different N regimes tested three times in field conditions during the 2015 growing season in two cultivars (‘Weiki’ and ‘Geneva’). Leaf total antioxidant capacity using ABTS, DPPH and FRAP tests was evaluated in the years 2015 to 2017, which experienced different weather conditions. Both cultivars exhibited a significant fall in leaf L-ascorbic acid (L-AA) and reduced glutathione (GSH) as well as global content of these compounds during the growing season, while total phenolic contents slightly (‘Weiki’) or significantly (‘Geneva’) increased. There was a large fluctuation in antioxidative enzyme activity during the season. The correlation between individual antioxidants and trolox equivalent antioxidant capacity (TEAC) depended on the plant development phase. The study revealed two peaks of an increase in TEAC at the start and end of the growing season. Leaf L-AA, global phenolics, APX, CAT and TEAC depended on the N level, but thiol compounds were not affected. Over the three years, TEAC decreased as soil N fertility increased, and the strength of the N effect was year dependent. The relationship between leaf N content and ABTS and FRAP tests was highly negative. The antioxidant properties of kiwiberry leaves were found to be closely related to the plant development phase and affected by soil N fertility.The aim of this study was to assess the enzymatic and non-enzymatic antioxidant status of kiwiberry ( Actinidia arguta (Siebold et Zucc.) Planch. ex Miq.), commonly known as kiwiberry, is a new product on the market that is experiencing growing consumer acceptance as well as an increasing area of production worldwide [A. arguta have also been evaluated in terms of biological activity [A. arguta leaves are proposed as a potentially valuable food additive that offers protection against many diseases caused by oxidative stress [Reactive oxygen species (ROS) and antioxidants are inherent elements in the metabolism of aerobes. ROS are produced during normal metabolic processes and serve as cell-signalling molecules . If theiorldwide . Kiwiberorldwide ,12 and iorldwide ,14,15. Torldwide . In factactivity ,18,19. Te stress ,19. Highe stress ,21.Arabidopsis thaliana L. leaves [Coffea arabica L. leaves [Vaccinium myrtillus L. [Plant antioxidant metabolism is genetically determined ,23,24,25. leaves  and Coff. leaves . Appropr. leaves . In turnillus L. . In summillus L. ,38. To eillus L. ,39.Actinidia arguta plants as a comprehensive source of food rich in bioactive compounds.Another important factor regarding tissue chemical content and composition is the plant development phase ,30,31,40Actinidia arguta) [Actinidia arguta leaves.A large amount of recent research has indicated leaves to be an extraordinary source of value-added compounds ,41,44,45 arguta) ,18,19. S arguta) ,44. Apar arguta) ,26,40,41A. arguta is a dioecious woody vine, leaf nutrient concentration varies not only by year or sampling date but also by plant gender and shoot type (determinate and indeterminate) for many tested nutrients [Plant antioxidant status provides important information about the plant metabolism in given environmental conditions ,46,47. Autrients . TherefoThe weather data collected throughout the experiment are presented in In detail, the time-dependent changes of the ascorbate and glutathione status, the concentration of L-cysteine (the precursor to glutathione) and global phenolics show A strong decrease in L-AA and total ascorbate (L-AA + DHAA) concentrations progressed with each time point at a very similar intensity for both cultivars A,B. SimiArabidopsis thaliana, while in coffee leaves a high activity of the enzymatic antioxidant system during the coffee fruit ripening stage was noted [A. arguta leaves and other fruit plant leaves is not presented in the literature.Looking at the changes in enzyme activity A–C, largas noted . In the Vaccinium ashei leaves sampled at the end of fruit ripening (December—late spring/early summer in Brazil) compared with those sampled in March (late summer/early autumn) [Vaccinium ashei leaf extract, the directions of changes were not as uniform between different cultivars. Therefore these changes may be dependent on the quali-quantitative leaf phenolic pattern of a given species or even cultivars. Quantitative and qualitative variations in phenolic content between species and cultivars are common phenomena [Much more research has been devoted to leaf phenolic content, both total concentration and individual compounds, and total antioxidant activity ,24,44,45 autumn) . However autumn) , such ashenomena ,15,54. Ihenomena . During henomena .Summarising this part of the results, it can be concluded that the ascorbate–glutathione cycle and related enzymes show large changes in concentration/activity, indicating a close relationship with the plant development cycle and high sensitivity to overall external conditions. Leaf global phenolic variation was rather low and cultivar dependent: in one cultivar, phenolic concentration did not change over the period tested and in the other, it significantly increased. However, it can be expected that the content of some individual phenolics may increase and others decrease ,30,46. TThe correlation between individual compounds and total antioxidant capacity as well as between leaf N contents and TEAC measured in different tests over three points of time in 2015 is presented in In turn, the relationship between leaf N content and TEAC measured using ABTS and FRAP assays was highly negative, especially at T2 point time. The opposite relationship occurred in the case of DPPH, namely the found correlation was positive .In view of the above results, research on antioxidant capacity continued in order to assess leaf biological value fluctuations based on ABTS, FRAP and DPPH tests, using the same cultivars as in the case of individual compounds and maintaining the same soil conditions in 2016–2017 A–F. The The interaction between the sampling time and N level did not in principle appear . The yeaHigh variability in consecutive years in the distribution of precipitation and temperature over the growing season, caused by climate change among other things, led to significant differences in the results of the open field study from year to year ,55. IrreCompared with FRAP and ABTS, the DPPH value C,D was rNutrient availability is a key controlling factor of biomass production and yield quality, but there are also increasing expectations in society for the development of an ecologically friendly management of mineral nutrition in agro-ecosystems . Althougp ≤ 0.05 (Tukey test). N1, N2, N3—30, 50 and 80 mg N kg−1 DW respectively; DHAA: dehydroascorbic acid. In this study, the N effect on the tested antioxidants was several times lower than the time of leaf sampling, and concerned only selected components  obtained in 2015. Values marked with a different letter in rows differ significantly at mponents . The dismponents . The N2 mponents ; Table 5ficiency . Ascorbificiency . Since aficiency .Coffea arabica L.) antioxidant enzymes  are more active in N-deficient plants, indicating a clear inverse relationship between antioxidant enzyme activities and applied N [a fluorescence measurements, ‘Weiki’ and ‘Geneva’ express different sensitivities to nitrogen deficiency [Lactuca sativa L.) with low N, Zhou et al. [In contrast, in coffee leaves  [The accumulation of phenolic compounds in plant tissues is often negatively affected by high N nutrition ,32,46. Ax Rchb.) . Regardix Rchb.) .Spinacia oleracea L. cv. Manatee) [This long-term study revealed an inverse relationship between increasing soil N level and antioxidant capacity . The cleManatee) . The resManatee)  suggest Manatee) .The recently described kiwiberry fruit antioxidants revealed that total ascorbate and glutathione pools were not dependent on soil N fertility, phenolic content or TEAC decreases, while enzymatic antioxidants were activated under the highest N dose . Compari−1, three soil N levels were chosen for examination in this experiment: 30 (N1), 50 (N2) and 80 (N3) mg N kg−1 of dry soil weight (DW). These are considered to be low, medium and high supply levels respectively. Plant rows were fertilised with ammonium nitrate (34% N) at the beginning of April and again four and eight weeks later in three equal doses. The weather data were collected throughout the experiment using the Vantage Pro2 Plus weather station . Weather data for the 2015–2017 seasons are presented in Leaf samples of ‘Weiki’ and ‘Geneva’ cultivars were acquired from the authors’ scientific project partner, the commercial A. arguta orchard located in Bodzew, Mazowieckie Voivodeship, Poland (51°47′49.9″ N + 20°48′44.0″ E) in 2015, 2016 and 2017. Examined cultivars varied with respect to leaf surface , while both cultivar show similar chlorophyll content . Both cuLeaf samples for antioxidant analysis were collected at three time points during the growing season, starting on 28 May in 2015, 2 June in 2016 and 8 June in 2017, and continuing every six weeks until the end of August (T1–T3 respectively). T1 represented the stage of fully developed leaves, T2 the peak of the most intensive fruit growth, and T3 the start of fruit physiological maturity (seed colour changed from white to brown). At each time point, three leaf samples per treatment were collected. Each sample consisted of 20 fully developed leaves collected from terminating shoots of female plants, located at the same height of the canopy. Terminating shoots end their growth quickly, so it can be assumed that in the following time point physiologically older leaves were sampled. Leaves of a similar size (for a given cultivar) were gathered evenly from shoots on both sides of each plant and represented the typical appearance for the particular N treatment. Leaves were frozen in liquid nitrogen and transferred to a freezer at −80 °C. The leaf samples were ground in mortars with liquid nitrogen to a fine powder before analysis.g or 48,000× g for determination of glutathione and ascorbate respectively. Total contents of glutathione (tGSH: GSH + GSSG) and L-cysteine (L-Cys) were measured in the supernatant after reduction with dithiothreitol (DTT) and derivatisation with monobromobimane. Monobromobimane derivatives were detected fluorometrically at 480 nm by excitation at 380 nm with a Waters 474 Scanning Fluorescence Detector . Oxidised glutathione (GSSG) was detected after the irreversible alkylation of the free thiol group of GSH with NEM and the following reduction of GSSG with DTT. Reduced glutathione (GSH) concentration was then calculated by subtracting the tGSH and GSSG results. Thiol derivatives were separated on a Luna C18 100 Å column  applying a solution of 10% methanol  and 90% methanol containing 0.25% (v/v) glacial acetic acid  at a flow rate of 1 mLmin−1. The concentration of L-ascorbic acid (L-AA) was analysed directly in the supernatant obtained after the extraction procedure. The total concentration of ascorbate  was measured after complete reduction of DHAA with DTT. Separation was carried out using an AtlantisTM dC18 column  coupled with a UV-VIS detector (Waters 2487) at 268 nm under isocratic conditions. The mobile phase contained 10% methanol and 2% NH4H2PO4 with a pH of 2.8. The concentrations of the above-mentioned compounds were calculated using a standard curve and expressed in mg*kg−1 FW.Thiol compounds and ascorbate. The concentration of ascorbate, glutathione and L-cysteine compounds was determined using high-performance liquid chromatography (HPLC) . First, −1 FW.Total phenolics content (TPC). TPC in leaf samples was measured with the Folin–Ciocalteu method  using a −1 FW .Trolox equivalent antioxidant capacity (TEAC). Three different well-documented tests were applied to evaluate TEAC in leaves: FRAP ,66, ABTSg for 20 min at 4 °C. The activity of APX , CAT  and GR  was measured spectrophotometrically  by monitoring the decrease in absorbance at 290 nm, 240 nm and 340 nm for APX, CAT and GR, respectively [−1 FW).Antioxidative enzyme activity. Leaf tissue powder was weighed (200 mg) and suspended in 100 mM potassium phosphate buffer  containing insoluble polyvinylpolypyrrolidone (PVPP), Triton X–100 (0.5%) and ascorbate (5 mM). The mixture was centrifuged at 48,000 http://statistica.io—access date 7 July 2017, USA). Due to varying weather conditions in each season and large differences in results between cultivars, each year’s results were elaborated separately for each cultivar tested. N level and leaf sampling time were the main factors. As the interaction between these factors did not in principle appear  using Statistica version 13.0 software  and the tested enzymatic and non-enzymatic antioxidants was performed .Actinidia arguta (Siebold et Zucc.) Planch. ex Miq.) leaf enzymatic and non-enzymatic antioxidants under different N regimes were tested three times in field conditions during the growing season for two commercially important cultivars (‘Weiki’ and ‘Geneva’). Leaf total antioxidant capacity using ABTS, DPPH and FRAP tests was evaluated over three years that experienced different weather conditions. In the context of fruit plant leaf antioxidant quality, there has been little examination previously of factors other than genetic ones, such as edaphoclimatic conditions, agronomic approaches or the plant development phase, and in the case of Actinidia arguta leaves, there appears to be no data at all. A research stimulus was that fruit leaves could be used as an extraordinary source of value-added compounds. The ascorbate–glutathione cycle and related enzymes  showed considerable changes in concentration/activity, indicating a close relationship with the plant development cycle and high sensitivity to overall external conditions. Leaf global phenolic variation was rather low throughout the growing season and was predominantly cultivar dependent. The strength of the correlation between individual antioxidants and TEAC at specific time points reflected antioxidant dynamics during the growing season. For most components tested, the close positive relationship in the case of ABTS and FRAP tests, but not DPPH, was revealed. Leaf L-AA, global phenolics, APX, CAT and TEAC also depended on the N level, while thiol compounds were not affected. Over the three years, TEAC decreased with increasing soil N fertility, and the intensity of the N effect was year dependent. These results suggest that the antioxidant properties of kiwiberry leaves are closely related to the plant development phase, which with proper N handling might be a suitable way for the acquisition of plant material with greater biological activity and potential health benefits.Kiwiberry (


Efficacy of pancreatic enzyme inhibitors in acute pancreatitis (AP) is unclear in China.We aimed to present the current status of AP and evaluate the efficacy of pancreatic enzyme inhibitors in a larger population in China.A retrospective, cross-sectional, real-world, multicenter analysis of a large dataset of patients presenting with AP from four hospitals of China over a two-year period was performed. Data were collected from the existing clinical records and the patients were grouped into medication group (somatostatin or octreotide or somatostatin and octreotide) and no medication group. Pair wise propensity score matching was performed for comparing somatostatin, octreotide and somatostatin/octreotide. The end points were incidence of disease complications, organ failure, hospitalization duration, and recovery time taken (hours) for serum amylase/serum lipase to normalcy.A total of 3900 patients were recruited and 2775 patients were included for analysis. A total of 1100, 661, 676 and 338 patients received either somatostatin or octreotide or somatostatin and octreotide or no medication, respectively. The incidence of complications (7.6% vs 13.6%), organ failure (4.5% vs 7.4%), and the instances of entering ICU (9.3% vs 13.3%) were higher in unmedicated group. Complications at discharge (2.91 times), organ failure (2.53 times), and hospitalization stay were higher in octreotide-treated patients compared with somatostatin-treated patients. In comparison to the octreotide group, the serum amylase/lipase recovery time was shorter in the somatostatin group.This real-world study suggested that the use of pancreatic enzyme inhibitors was positively associated with greater clinical efficacy in AP patients and somatostatin might be more effective than octreotide in real-world settings in China.The online version contains supplementary material available at 10.1186/s12876-021-01799-1. Acute pancreatitis (AP) is a gastrointestinal disease caused by sudden edema of pancreas that may lead to multiorgan failure or death. In the past few decades, the incidence of AP is on the rise throughout the world –4. In maGenerally, mild AP is treated using supportive care measures. Moderate AP and SAP are treated with pharmacological interventions to decrease the morbidity and mortality rates . SomatosThis study was designed as a real-world, retrospective, cross-sectional, multicenter study on patients hospitalized with AP in different regions of China. Electronic medical records (EMR) from multiple hospitals in different regions of China  were extracted. The four hospitals were: The First Hospital of China Medical University, The First Affiliated Hospital of Fujian Medical University, The Affiliated Hospital of Qingdao Medical University, and The Affiliated Hospital of Guizhou Medical University. All these hospitals are tier-3 affiliated hospitals  of medical universities. This study was approved by the respective ethical committee from the individual hospitals and was done in compliance with the Chinese laws before study initiation.Patients hospitalized between January 1, 2016 and December 31, 2017 with confirmative diagnosis for AP were included in this study  using the Data Process & Application Platform (DPAP) account. All the data were collected from the existing clinical records of 42 departments comprising of 5,363 EMR data, 32,279 lab data (AMY/LPS) and 6,608 abdominal CT images. The details of demographic characteristics, disease characteristics, treatment, and prognosis of all eligible AP patients were extracted from the database and structured into a standard data model.Treatment groups were divided into four based on supportive medication types for pancreatic exocrine and enzyme inhibition from medical records: somatostatin, octreotide, somatostatin + octreotide and ‘no-medication’ (no use of pancreatic exocrine and enzyme inhibitors). The effectiveness comparisons were performed at two steps: First, we compared the acid and pancreatic exocrine and enzyme inhibitors treatment groups with the no-medication group; The comparison was then conducted between the somatostatin, octreotide and somatostatin + octreotide groups. In the “somatostatin + octreotide” group, patients who received both somatostatin and octreotide during the hospital stay were included. Demographics and disease characteristics were summarized for AP status and management. Treatment outcomes were measured as incidence of disease complications and organ failure. Disease complications were defined as both local complications and systemic complications. Local complications include in detail as follow: acute fluid accumulation, acute necrotic accumulation, pancreatic pseudocyst, encapsulated necrosis, pancreatic abscess, gastrointestinal fistula; systemic complications include: organ failure, systemic inflammatory response syndrome (SIRS), systemic infection, intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and pancreatic encephalopathy (PE). Organ failure was defined as renal failure, respiratory failure, shock, multiple organ dysfunction syndrome (MODS) and multiple organ failure (MOF).P < 0.05 considered as significant.Continuous data were represented as mean, median, and standard deviation. Student’s t-test and the Wilcoxon rank sum test were used for calculating statistical significance for normal and skewed distributions, respectively. Analysis of variance was used to compare statistical difference among different treatment groups for analysis of continuous data. For binary outcomes, disease complication and organ failure, the multivariate logistic regression analyses were performed to evaluate the association between drug treatment groups and each outcome. The factors associated with a prolonged length of hospital stay were determined by logarithmic linear regression analysis. The covariates in the multivariate models include drinking history, etiology, diabetes history, and severity at admission. Furthermore, propensity score matching (PSM) was performed to balance the differences in baseline characteristics as well as to reduce the effects of confounders. Logistic regression model was used to calculate the propensity scores. All statistical analyses were performed using R version 3.4.1 with a During the two-year study period, a total of 5363 patients were hospitalized with pancreatitis and 3900 were diagnosed with AP. The baseline characteristics, demographic details and etiology were summarized in Table Out of 3900 patients, 781 patients with a disease course of more than 7 days or with uncertain disease course, 93 patients with missing smoking/ drinking data and 251 patients with less than 2 days of treatment, were excluded from effectiveness analysis. Among the remaining 2775 patients 2437 were divided in to three group namely somatostatin group (N = 1100), Octreotide group (N = 661) and somatostatin/Octreotide group (N = 676) and received their respective treatments and remaining 338 did not received any medication  received somatostatin alone, 661 (27.1%) received octreotide, and 676 (27.7%) patients received somatostatin/octreotide .P < 0.05) (Supplementary Table 1).In order to assess the necessity and to compare the pharmacologic therapeutic efficacy of AP, treatment outcomes of patients who did not receive any medication (n = 338) were compared with patients who received single pharmacologic treatment (n = 1761). Patients treated with both octreotide and somatostatin were not included due to lack of data regarding the sequence of usage. While the median hospitalization days were more in patients who received medication (12 vs 9), the incidence of complications (7.6% vs 13.6%), organ failure (4.5% vs 7.4%), and the instances of entering ICU (9.3% vs 13.3%) was higher in patients in ‘no-medication’ group. Statistical significance was observed for hospitalization days, complications, organ failure and entering ICU (p = 0.017). Similarly, statistically significant difference in the incidence of complications in the somatostatin/octreotide group to be 1.828 times higher than in the somatostatin group  . Similarly, a statistically significant increase in the risk of incidence of complication was observed in the somatostatin + octreotide group (OR (95% CI) 1.696  (p = 0.011) in comparison to somatostatin group (Table Complications due to AP occurred in 77 (7.0%) patients in the somatostatin group, 57 (8.6%) patients in the octreotide group, and 74 (10.9%) patients in the somatostatin + octreotide group. Multivariable analysis  revealed significant difference in the incidence of complications in the octreotide group to be 1.582 times higher than that in the somatostatin group . However, the incidence of organ failure was 1.7 times significantly higher in the somatostatin + octreotide group compared with the somatostatin group  ) when compared to somatostatin group. Furthermore, a non-significant increase in the incidence of organ failure was observed in somatostatin + octreotide group (OR (95% CI) 1.553  (p = 0.093) when compared with somatostatin group (Table Organ failure occurred in 50 (4.5%), 29 (4.4%), and 45 (6.7%) patients in the somatostatin group, the octreotide group, and the somatostatin + octreotide group, respectively. Multivariable analysis revealed the incidence of organ failure in the octreotide group to be 1.3 times higher than that in the somatostatin group   and the somatostatin + octreotide group (p < 0.001), respectively (Supplementary Table 2).Of the 2437 hospitalized AP patients, 2401 patients were included for analysis after excluding patients who died or gave up treatment during hospitalization. The median hospitalization duration was 11 days [IQR: 8–16 days] for the somatostatin group, 12 days [IQR: 9–17 days] for the octreotide group, and 13 days [IQR: 9–19 days] for the somatostatin + octreotide group. Statistically significant differences were observed among the octreotide group and the somatostatin group, the octreotide/somatostatin group and the somatostatin group  and the somatostatin + octreotide group   for 351 patients in the somatostatin group, 84.88 h (IQR: 59.47–116.45 h) for 204 patients in the octreotide group, and 86.61 h (IQR: 61.54–131.73 h) for 240 patients in the somatostatin + octreotide group. In multivariable analysis (after controlling the confounding of the severity and CCI at admission), the recovery time of AMY in the somatostatin group was significantly shorter than the octreotide group .  for 73 patients in the somatostatin group, 109.220 h (IQR: 61.00–139.29 h) for 80 patients in the octreotide group, and 90.99 h (IQR: 63.53–155.94 h) for 112 patients in the somatostatin + octreotide group. Multivariable analysis revealed no significant difference between three treatment groups  which increases the internal validity of the dataset. We also compared the efficacy of pharmacologic treatment of AP with non-pharmacologic management (medication vs no medication). The results of our study suggested improved outcomes in patients treated with any medication, and among the medications used somatostatin was found to provide better efficacy.The role of pancreatic enzyme inhibitors in the treatment of AP remains unclear. However, several national clinical guidelines exist for the diagnosis and management of AP. But compliance to the recommendations is at the discretion of the treating physicians in different countries. A Japanese guidelines published in 2015, focused on the epidemiology, diagnosis, severity, treatment, post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators but did not provide any specific recommendation on the use of pancreatic enzyme inhibitors . WhereasIn the current study, we found pancreatic exocrine and enzyme inhibition to be effective in controlling rates of complications, organ failure and instances of ICU admission. A previous study with high-dose octreotide as the intervention reported significant reduction in instances of organ failure (44% vs. 66%) . SimilarInvestigations on somatostatin and its analogs in several experimental models of AP showed confounding results. A probable reason could be the diverse endpoints used to assess efficacy and also the underlying cause of AP in the analyzed patients. Since the clinical decision of managing AP in real-world settings is made on a case-to-case basis, there are practical issues with conducting randomized controlled trials evaluating somatostatin and octreotide . The effWith recent advancement in treatment , the lenTo the best of our knowledge, this is the first study to use extensive data generated by big data analysis platform’s uniform EMR for the management of AP in China. This real-world data provided high-quality evidence in the current status of management of AP patients in China. Further, there are no real-world data available for the comparison of somatostatin, octreotide, and somatostatin + octreotide in the pharmacologic management of AP. Based on this real-world evidence from China, somatostatin might be effective than octreotide with respect to both the efficacy and complications at discharge in the patients hospitalized with AP.The main strength of the study is large and real-world data from different regions of China used for the analysis. This broader the view of risk–benefit profile of somatostatin analogs used in the management of AP. The endpoints analyzed were comprehensive encompassing both efficacy and current status of patients with AP in China.Some limitations should be noted when interpreting the results. First, some patients with key information missing were excluded from the analysis, which led to a reduction in the sample size. Another limitation relates to the retrospective nature of the study and limited information recorded in the system; for example, dosage details of medication and meal start time were not captured by the electronic health record in a comprehensive manner, which prevented further assessment and might have an impact on the results to some degree.Additional file 1.Supplementary Table 1. Therapeutic Outcomes in Patients Treated With and Without acid and enzyme inhibition Medication. Supplementary Table 2. Hospitalization Days in Different Treatment Groups . Supplementary Table 3. Matched baseline characteristics comparison between somatostatin vs octreotide in propensity score matching analysis. Supplementary Table 4. Matched baseline characteristics comparison between somatostatin vs octreotide+somatostatin in propensity score matching analysis.


Background: Thrombus perviousness (TP) quantified by thrombus attenuation increase (TAI) assessed on acute non-contrast computed tomography (NCCT) and CT angiography (CTA) may be associated with stroke etiology in anterior circulation ischemic stroke. We investigated whether TP is associated with stroke etiology and recanalization after mechanical thrombectomy in patients with acute basilar artery occlusion (BAO).Methods: Eighty patients with complete BAO and in-house acute imaging from a prospectively maintained database were included. Two raters independently segmented the complete thrombus on co-registered NCCT and CTA to determine TAI in Hounsfield units (HUCTA–HUNCCT); averaged values of the raters were used for analysis. Recanalization to modified treatment in cerebral ischemia (mTICI) score 2b/3 was considered successful, and 90-day modified Rankin Scale score 0–2 was considered favorable.Results: TAI did not differ between patients with different stroke etiologies; median TAI in patients with cardioembolic stroke (n = 36) was −0.47 (interquartile range −4.08 to 7.72), 1.94 (−8.14 to 10.75) in patients with large artery atherosclerosis , and −0.99 (−6.49 to 5.40) in patients with stroke of undetermined origin . Binary logistic regression analyses did not identify TAI as an independent indicator of cardioembolic stroke . There was no association with successful recanalization  or favorable outcome .Conclusion: In contrast to proximal middle cerebral artery occlusions, TP in BAO patients is not associated with cardioembolic stroke etiology. Larger confirmatory studies to establish the potential role of TP for clinical applications should focus on patients with anterior circulation stroke. Basilar artery (BA) occlusion (BAO) is less frequent than anterior circulation stroke and occurs in approximately 10% of all patients with large vessel occlusions . While oIn patients with acute stroke and occlusion of the proximal M1 segment of the middle cerebral artery (MCA), thrombus perviousness (TP)—quantified by thrombus attenuation increase (TAI) on computed tomography (CT) angiography (CTA) relative to non-contrast CT (NCCT)—is associated with cardioembolic stroke etiology , 7. In tThe raw data are not publicly available, as they contain information that could compromise patient privacy; anonymized summary data can be provided by the corresponding author upon reasonable request.We performed an investigator-initiated retrospective study including patients from three different sites of our university hospital. Acute ischemic stroke with BAO enrolled in our prospectively maintained in-house database of consecutive patients undergoing EVT between 2015 and 2020 were eligible for inclusion. Inclusion criteria were as follows: NCCT and CTA on admission in a single session, showing complete BAO, and no administration of intravenous thrombolysis before imaging. Clinical data including demographic baseline data, presumed stroke etiology according to the trial of ORG 10172 in acute stroke treatment , and recanalization status were extracted from the database. Recanalization to modified treatment in cerebral ischemia (mTICI) score ≤ 2b/3 was considered successful, and 90-day mRS score 0–2 was considered favorable.https://www.nitrc.org/projects/mricron).Image analysis was performed as described previously . BrieflyTP was compared between groups using the Kruskal–Wallis test; proportions were compared using analysis of (co-)variance. We calculated multivariable binary logistic regression models including age, sex, and arterial hypertension  to test for a significant association between cardioembolic stroke etiology and outcome. Concordance between readers was quantified as intraclass correlation and determined using a two-way mixed model.The study was designed and conducted in agreement with laws and regulations in the Federal State of Berlin according to which ethics committee approval and patient consent were not required for this retrospective study.N = 36) were older and had higher rates of atrial fibrillation and arterial hypertension. Two patients had stroke of other determined etiology . Intravenous thrombolysis with recombinant tissue plasminogen activator at a dose of 0.9 mg per kg body weight was administered in 50% of all patients. In all patients, endovascular clot removal was attempted, mostly with a Sofia 6F (Plus), a Sofia 5F, or a Trevo device.One hundred sixty-nine patients with a diagnosis of BAO were screened, of which 80 were included in the final analysis . Descripp = 0.955; There was no association between TP and stroke etiology: median (interquartile range [IQR]) values of TAI in patients with cardioembolic stroke, LAA stroke, stroke of undetermined origin, and stroke other determined etiology were −0.47 (−4.08 to 7.72), 1.94 (−8.14 to 10.75), −0.99 (−6.49 to 5.40), and −0.47 (−1.86 to 0.92), respectively . Median thrombus volume was 45.3 mm3 (IQR = 27.0–68.4) and did not differ between groups (p = 0.942).Mean thrombus density ranged from 22.1 to 74.7 HU . There was no association between thrombus density and stroke etiology (p = 0.155). Following adjustment for age, sex, and stroke etiology, TP had a crude OR of 1.5  and adjusted OR of 1.39 (0.70–2.7), p = 0.345) for successful recanalization. In a subgroup of 24 patients with available 90-day mRS, TP had a crude and adjusted OR for favorable outcome (mRS ≤ 2) of 1.05  and 1.1 .Seventy-three patients were successfully recanalized by treatment. TP was nominally lower in recanalizers compared with non-recanalizers  . BrieflyInterestingly, previous studies found that high TAI values in patients with M1 occlusion were associated with cardioembolic stroke etiology , 7. TherIt was recently suggested that TP might differentiate between BAO with and without underlying basilar stenosis . In our The primary limitations of this study include its retrospective nature and relatively small sample size, which increase the likelihood of type II errors. Nonetheless, considering BAO makes up only ~2% of all acute ischemic strokes  Clinical Scientist Program funded by the Charité—Universitätsmedizin Berlin and the Berlin Institute of Health. ME received funding from Deutsche Forschungsgemeinschaft  under Germany's Excellence Strategy—EXC-2049-390688087 and from Bundesministerium für Bildung und Forschung  for the Center for Stroke Research Berlin. CL is a participant in the Berlin Institute of Health-Charité Clinical Fellow Program funded by the Charité—Universitätsmedizin Berlin and the Berlin Institute of Health.ME reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, Sanofi, Novartis, and Pfizer, all outside the submitted work. MS reports no conflicts of interest related to this work. He is a patent holder and shareholder of PhantomX a company producing 3D models for CT. CL reports personal fees from Edwards Lifesciences and fees paid to Charité from Bard, Zoll, and Pfizer, all outside the submitted work. CN reports personal fees from Boehringer Ingelheim, Pfizer Pharma, Britsol-Myers Squibb, Abbott, and Portola, outside the submitted work. LS reports personal fees from Daiichi Sankyo, outside the submitted work. The remaining author declares 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.