Composing functional food from agro-forest wastes: Selectively extracting bioactive compounds using supercritical fluid extraction.

Supercritical fluid extraction (SFE) employing carbon dioxide (SC-CO2) is an efficient method to extract bioactive compounds from agro-forest wastes. These compounds maintain and/or improve food nutrition, safety, freshness, taste, and health and are employed as natural functional food components. To highlight the potential of this technology, we focus on the following current advances: (I) parameters affecting solubility in SFE (pressure, temperature, SC-CO2 flow rate, extraction time, and co-solvents); (II) extraction spectra and yield obtained according to proportion and composition of co-solvents; (III) extract bioactivity for functional food production. Fatty acids, monoterpenes, sesquiterpenes, diterpenoids, and low-polarity phenolic acids and triterpenoids were extracted using SFE without a co-solvent. High-polarity phenolic acids and flavonoids, tannins, carotenoids, and alkaloids were only extracted with the help of co-solvents. Using a co-solvent significantly improved the triterpenoid, flavonoid, and phenolic acid yield with a medium polarity.

Comparison of clinical effects of coronary artery bypass grafting between left anterior small thoracotomy approach and lower-end sternal splitting approach.

OBJECTIVE: To compare the clinical effects of coronary artery bypass grafting (CABG) between the left anterior small thoracotomy (LAST) and lower-end sternal splitting (LESS) approaches for coronary artery disease. METHODS: In total, 110 patients who underwent LAST from October 2015 to December 2020 in Tianjin Chest Hospital were selected as the observation group. Patients who underwent the LESS approach during the same period were analyzed. The propensity score was calculated by a logistic regression model, and nearest-neighbor matching was used for 1:1 matching. RESULTS: The length of hospital stay and ventilator support time were significantly shorter in the LAST than LESS group. The target vessels in the obtuse marginal branch and posterior left ventricular artery branch grafts were significantly more numerous in the LAST than LESS group, but those in the right coronary artery graft were significantly less numerous in the LAST group. CONCLUSIONS: CABG using either the LAST or LESS approach is safe and effective, especially in low-risk patients. The LAST approach can achieve complete revascularization for multivessel lesions and has the advantages of less trauma and an aesthetic outcome. However, it requires a certain learning curve to master the surgical techniques and has specific surgical indications.

The antibacterial and antialgal enhancement of the hydroquinone acrylamide polyurethane coating based on microphase separation.

The undesirable and inevitable adhesion of marine organisms on submerged surfaces has seriously affect the environment, economy and society, so emerging and promising strategies for antifouling are required. Here, the novel and environmental strategy of the antibacterial and antialgal materials was proposed for the application of the antifouling coating without releasing harmful substances. The environment-friendly antifouling agent, the capsaicin derivative N-(2,5-dihydroxy-4-acrylamide meth-ylbenzyl)acrylamide (PHABA), was modified to the molecular chain of the polyurethane. The best tensile strength was up to 23.5 MPa of PUP-25% and the elongation at break was 415% of PUP-25%. The excellent wear resistance (300 wear cycles) and chemical solution resistance (H2SO4, NaOH, and NaCl solutions) revealed the applicability of the coating. PHABA would migrate to the surface of the polyurethane coating with time and enhanced the antibacterial and antialgal properties of the coating. PUP-25% prevented more than 90% of bacterial and algal adhesion, indicating the potential application of the antifouling coating.

Generation mechanism and empirical model of eddy current force and torque in drum-type eddy current separation.

Enhancing the recovery efficiency of non-ferrous metals in eddy current separation is of great significance. In this study, the accuracy of the simulation model was verified by comparing the eddy current force. The transformation mechanism of the Lorentz forces into the eddy current force and torque in non-ferrous metal particles was revealed by analyzing various physical fields. Then, the influence of magnetic field parameters on eddy current, eddy current force, and torque was studied. It shows that the eddy current force and torque are affected by the vector gradient of the magnetic field and the magnetic flux density, respectively. Additionally, the time derivative of the magnetic field impacts the magnitude of the eddy current force and torque by controlling the eddy current. On this basis, the empirical models of eddy current force and torque were established by similarity theory. The results obtained can improve and expand the application of eddy current separation.

Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics" / 药学学报

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension in mice and its mechanism / 中国药理学通报

Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

High-quality acceleration of the Chinese national schistosomiasis elimination programme to advance the building of Healthy China / 中国血吸虫病防治杂志

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

Risk prediction models of dangerous behaviors among patients with severe mental disorder in community / 四川精神卫生

BackgroundThe occurrence rate of dangerous behaviors in patients with severe mental disorders is higher than that of the general population. In China， there is limited research on the prediction of dangerous behaviors in community-dwelling patients with severe mental disorders， particularly in terms of predicting models using data mining techniques other than traditional methods. ObjectiveTo explore the influencing factors of dangerous behaviors in community-dwelling patients with severe mental disorders and testing whether the classification decision tree model is superior to the Logistic regression model. MethodsA total of 11 484 community-dwelling patients with severe mental disorders who had complete follow-up records from 2013 to 2022 were selected on December 2023. The data were divided into a training set （n=9 186） and a testing set （n=2 298） in an 8∶2 ratio. Logistic regression and classification decision trees were separately used to establish predictive models in the training set. Model discrimination and calibration were evaluated in the testing set. ResultsDuring the follow-up period， 1 115 cases （9.71%） exhibited dangerous behaviors. Logistic regression results showed that urban residence， poverty， guardianship， intellectual disability， history of dangerous behaviors， impaired insight and positive symptoms were risk factors for dangerous behaviors （OR=1.778， 1.459， 2.719， 1.483， 3.890， 1.423， 2.528， 2.124， P<0.01）. Being aged ≥60 years， educated， not requiring prescribed medication and having normal social functioning were protective factors for dangerous behaviors （OR=0.594， 0.824， 0.422， 0.719， P<0.05 or 0.01）. The predictive effect in the testing set showed an area under curve （AUC） of 0.729 （95% CI： 0.692~0.766）， accuracy of 70.97%， sensitivity of 59.71%， and specificity of 72.05%. The classification decision tree results showed that past dangerous situations， positive symptoms， overall social functioning score， economic status， insight， household registration， disability status and age were the influencing factors for dangerous behaviors. The predictive effect in the testing set showed an AUC of 0.721 （95% CI： 0.705~0.737）， accuracy of 68.28%， sensitivity of 64.46%， and specificity of 68.60%. ConclusionThe classification decision tree does not have a greater advantage over the logistic regression model in predicting the risk of dangerous behaviors in patients with severe mental disorders in the community. ［Funded by Chengdu Medical Research Project （number， 2020052）］

The enhanced cytotoxicity on breast cancer cells by Tanshinone I-induced photodynamic effect.

Recently, natural photosensitizers, such as berberine, curcumin, riboflavin, and emodin, have received more and more attention in photodynamic therapy. Tanshinone I (TanI) is extracted from a traditional Chinese herb Danshen, and exhibits many physiological functions including antitumor. TanI is a photoactive phytocompounds, but no work was tried to investigate its potential photodynamic effect. This study evaluated the cytotoxicity induced by the photodynamic effect of TanI. The photochemical reactions of TanI were firstly investigated by laser flash photolysis. Then breast cancer cell line MDA-MB-231 was chosen as a model and the photodynamic effect of TanI on cancer cell was evaluated by MTT assay and flow cytometry. The results showed that TanI could be photoexcited by its UV-Vis absorption light to produce 3TanI* which was quickly quenched by O2. MTT assay showed that the photodynamic effect of TanI resulted in more obvious inhibitive effect on cell survival and cell migration. Besides, the photodynamic effect of TanI could induce cell apoptosis and necrosis, lead to cell cycle arrest in G2, increase intracellular ROS, and decrease the cellular Δψm. It can be concluded that the photodynamic effect of TanI can obviously enhance the cytotoxicity of TanI on MDA-MB-231 cells in vitro, which indicated that TanI might serve as a natural photosensitizer.

Reduction in the duration of postoperative fever following NUSS surgery during the COVID-19 pandemic.

BACKGROUND: Our study aimed to compare the prevalence of postoperative fever during the COVID-19 pandemic period with that of the preceding non-pandemic period. METHODS: A retrospective analysis was conducted on patients with pectus excavatum (PE) undergoing minimally invasive repair (also called NUSS procedure) at Nanjing Children's Hospital from January 1, 2017 to March 1, 2019 (Group 2019), and from January 1, 2020 to March 1, 2021 (Group 2021). Data from a total of 284 patients, consisting of 200 (70.4%) males and 84 (29.6%) females with an average age of 9.73 ± 3.41 (range, 4 to 17) years, were collected. The presence of post-operative fever (defined as a forehead temperature of 37.5℃ or above within 72 h post-surgery), as well as the time of operation, duration of postoperative mechanical ventilator and urinary catheter use, and length of hospitalization were all assessed in admitted patients from Group 2019 (n = 144) and Group 2021 (n = 140). Postoperative white blood cell (WBC), C-reactive protein (CRP) levels, and prevalence of postoperative complications (i.e., pneumothorax, pulmonary atelectasis, pneumonia, wound infection, and dehiscence) were also determined. RESULT: Our results showed a statistically significant decrease in the incidence of postoperative fever within 24 to 72 h of surgery in patients admitted from Group 2019 as compared to Group 2021 (p < 0.001), as well as a decrease in peak body temperature within 72 h (p < 0.05). Meanwhile, no significant differences were observed in age and body mass index (BMI), time of operation, or duration of postoperative mechanical ventilator and urinary catheter use between the two groups (p > 0.05). The average hospitalization length of Group 2021 was significantly shorter than Group 2019 (12.49 ± 2.57 vs. 11.85 ± 2.19 days, p < 0.05). Furthermore, while the WBC count between the two groups 24 h after surgery showed a statistical difference (p < 0.05), no differences in CRP levels or the incidence of postoperative complications were observed (p > 0.05). CONCLUSION: The prevalence of postoperative fever within 72 h of surgery and the length of hospital stay for patients with PE undergoing NUSS surgery were both decreased in Group 2021. We propose that the above phenomenon may be related to increased used of personal protection equipment (such as surgical masks and filtering facepiece respirators (FFRs)) by physicians, nurses, and the patients themselves.

The effect of robot-assisted gait training for patients with spinal cord injury: a systematic review and meta-analysis.

Background: With the aging of the global population, Spinal injuries are often prone to occur and affect human health. The development of technology has put robots on the stage to assist in the treatment of spinal injuries. Methods: A comprehensive literature search were carried out in multiple databases, including PubMed, Medline (Ovid), Web of Science, Cochrane, Embase, Scopus, CKNI, Wang fang, VIP database, Sino Med, Clinical Trails until 20th, June, 2023 to collect effect of robot-assisted gait training for patients with spinal cord injury patients. Primary outcome includes any changes of gait distance and gait speed. Secondary outcomes include any changes in functions (Such as TUG, Leg strength, 10 MWT) and any advent events. Data were extracted from two independent individuals and Cochrane Risk of Bias tool version 2.0 was assessed for the included studies. Systematic review and meta-analysis were performed by RevMan 5.3 software. Results: 11 studies were included in meta-analysis. The result showed that gait distance [WMD = 16.05, 95% CI (-15.73, 47.83), I2 = 69%], gait speed (RAGT vs. regular treatment) [WMD = 0.01, 95% CI (-0.04, 0.05), I2 = 43%], gait speed (RAGT vs. no intervention) [WMD = 0.07, 95% CI (0.01, 0.12), I2 = 0%], leg strength [WMD = 0.59, 95% CI (-1.22, 2.40), I2 = 29%], TUG [WMD = 9.25, 95% CI (2.76, 15.73), I2 = 74%], 10 MWT [WMD = 0.01, 95% CI (-0.15, 0.16), I2 = 0%], and 6 MWT [WMD = 1.79, 95% CI (-21.32, 24.90), I2 = 0%]. Conclusion: Robot-assisted gait training seems to be helpful for patients with spinal cord to improve TUG. It may not affect gait distance, gait speed, leg strength, 10 MWT, and 6 MWT.

Lack of furosemide responsiveness predict severe acute kidney injury after liver transplantation.

Acute kidney injury (AKI) remains to be a common but severe complication after liver transplantation (LT). However, there are still few clinically validated biomarkers. A total of 214 patients who underwent routine furosemide (1-2 mg/kg) after LT were retrospectively included. The urine output during the first 6 h was recorded to evaluate the predictive value of AKI stage 3 and renal replacement therapy (RRT). 105 (49.07%) patients developed AKI, including 21 (9.81%) progression to AKI stage 3 and 10 (4.67%) requiring RRT. The urine output decreased with the increasing severity of AKI. The urine output of AKI stage 3 did not significantly increase after the use of furosemide. The area under the receiver operator characteristic (ROC) curves for the total urine output in the first hour to predict progression to AKI stage 3 was 0.94 (p < 0.001). The ideal cutoff for predicting AKI progression during the first hour was a urine volume of less than 200 ml with a sensitivity of 90.48% and specificity of 86.53%. The area under the ROC curves for the total urine output in the six hours to predict progression to RRT was 0.944 (p < 0.001). The ideal cutoff was a urine volume of less than 500 ml with a sensitivity of 90% and specificity of 90.91%. Severe AKI after liver transplantation seriously affects the outcome of patients. Lack of furosemide responsiveness quickly and accurately predict AKI stage 3, and patients requiring RRT after the operation.

Finite element analysis of 14-year-old adolescent after spinal foraminoplasty at L / 解剖学报

Objective To establish the three-dimensional finite element model of lumbar spine(L) 3-5 segments of the normal spine of 14-year-old adolescents to analyze the biomechanical changes of the lumbar spine after different degrees of lumbar foraminal plasty, and to provide reference for improvement of adolescent foraminoplasty. Methods A14-year-old female volunteer with no previous history of lumbar spine was selected to collect lumbar CT image data and we imported it into Mimics 16.0 software for modeling. ABAQUS software was used to conduct finite element model force analysis. Models M

Progress on the pathological mechanism and treatment of frostbite / 中国临床药理学与治疗学

Frostbite is a tissue injury that occurs when the body is exposed to extreme cold. Its pathological mechanism is complex and has not been fully elucidated. In high cold and high altitude areas, outdoor sports people have a high risk of injury, and severe frostbite has high disability and mortality. Exploring the pathological mechanism of frostbite is helpful to determine the treatment methods and timing. At present, the clinical treatment of frostbite is mainly symptomatic treatment, such as drug treatment and surgical treatment, but the curative effect can not meet the clinical needs. Therefore, it is of great significance to seek more efficient drugs or treatment methods. This article reviews the relevant research progress in pathophysiological mechanism, clinical treatment, cellular and molecular pathways of frostbite in recent years, in order to provide new ideas for future research and clinical treatment.

Role and mechanism of NR1D1 in proliferation and migration of vascular adventitial fibroblasts / 中国药理学通报

Aim To explore the role and mechanism of nuclear receptor subfamily 1,group D,member 1(NR1D1)in the proliferation and migration of mouse adventitial fibroblasts(AFs). Methods Primary AFs isolated from C57BL/6J mice were cultured. Adenovirus carrying Nr1d1 gene was used to overexpress NR1D1 in AFs. The expression of β-catenin was restored by SKL2001. Proliferating cell nuclear antigen(Ki-67)immunofluorescence staining and CCK-8 staining were used to determine cell proliferation,and scratch test was used to determine cell migration. qPCR was used to determine the mRNA level of Nr1d1. Western blot was used to determine the protein levels of NR1D1 and β-catenin. To investigate the role of NR1D1 in intimal hyperplasia,20 male wild type C57BL/6J mice were randomly divided into sham group,carotid artery endothelial injury,sham+SR9009(NR1D1 agonist)group and carotid artery endothelial injury+SR9009(n=5 in each group). They were treated with DMSO or SR9009(100 mg·kg-1·d-1)via intraperitoneal injection for 14 days after operation,respectively. The degree of carotid intimal hyperplasia was measured by HE staining 28 days after operation. Results NR1D1 overexpression significantly reduced the percentage of Ki-67-positive cells(P<0.01),total cell number(P<0.01)and slowed down the rate of wound-healing(P<0.01). NR1D1 overexpression significantly inhibited the expression of β-catenin(P<0.05). After the expression of β-catenin was restored by SKL2001,the inhibitory effects of NR1D1 overexpression on the proliferation and migration of AFs were abolished(P<0.01). Enhanced activity of NR1D1 significantly ameliorated intimal hyperplasia after carotid endothelial injury(P<0.01). Conclusion NR1D1 may inhibit the proliferation and migration of AFs via suppressing the expression of β-catenin.

Prostate cancer with normal serum PSA: a report of 6 cases and literature review / 现代泌尿外科杂志

【Objective】 To analyze the clinical data of prostate cancer patients with normal PSA level confirmed with transperineal prostate biopsy or transurethral prostate surgery, in order to improve the diagnostic level of this disease. 【Methods】 The clinical data of 6 patients were retrospectively analyzed. The age,clinical manifestations, body mass index (BMI),prostate specific antigen density (PSAD),blood triglycerides,blood cholesterol,color ultrasound imaging,magnetic resonance imaging (MRI),pathological types and Gleason scores were analyzed. The clinical characteristics and high-risk factors were summarized. 【Results】 Two cases were confirmed with prostate biopsy and four after prostate resection. Three patients had high blood triglycerides, three were negative for bone imaging, and the other three were not examined. PSAD was 0.017 to 1.215. Color ultrasound indicated that two cases had irregular morphology, two uneven echo, and one both irregular morphology and uneven echo; all six cases had calcification. In the three cases who received MRI, two had PIRADS4 nodules, one had PIRADS5 nodules, invasion of seminal vesicle, rectum, posterior wall of urinary bladder,bilateral thickening of NVB, and lymph nodes enlargement. Pathology suggested prostatic acinar adenocarcinoma in five cases, four of which had a Gleason score of 3+3=6 and one had 5+5=10; one case suggested a high-grade neuroendocrine carcinoma. 【Conclusion】 The clinical detection rate is low for prostate cancer with normal PSA. The biopsy indications should be determined by combining the characteristics and high-risk factors to improve the detection rate.

Application of semiconductor blue laser in day surgery for 22 cases of bladder cancer / 现代泌尿外科杂志

【Objective】 To investigate the feasibility and safety of semiconductor blue laser in the treatment of non-muscle invasive bladder cancer (NMIBC) in the day surgery model. 【Methods】 The clinical data of 22 NMIBC patients (average age 55.8 years and tumor size 1.4 cm) who underwent outpatient screening and accepted blue laser ambulatory surgery in our hospital during Jun.2022 and Sep.2022 were retrospectively analyzed. On the day of admission, transurethral resection of cancer was performed using blue laser en bloc enucleation. On the day of surgery or in the morning of next day, bladder irrigation was stopped, the catheter was removed, and patients were discharged. The baseline data, pre-hospital waiting time, operation time, length of hospital stay, hemoglobin decrease, complications and management, follow-up, medical costs, and patients’ satisfaction rate were recorded. 【Results】 The pre-hospital waiting time was 2 to 7 days, average (4.1±1.3)days. The operation time was 29 to 50 minutes, average (40.8±5.5)minutes. The length of hospital stay was 0.6 to 1.2 days, average (0.9±0.2)days. Hemoglobin decrease was 1 g/L to 8 g/L, average (3.8±1.8)g/L. The catheter was indwelt for 0.5 to 1 day, average (0.7±0.1)day. The medical costs were 13 790 to 16 811 Yuan, average (14 941.5±690.2) Yuan. Patients’ satisfaction rate was 100.0%. Mild intraoperative and postoperative complications occurred in 2 cases. One patient developed symptoms of cystitis which disappeared after 2 days of oral antibiotic cefixime, and another patient developed bladder spasm which was relieved after oral solifenacin succinate tablets. No adverse events such as obturator nerve reflex or bladder perforation occurred. After removal of the catheter, no urinary retention was observed. 【Conclusion】 This study was the first to apply blue laser ambulatory surgery in the treatment of bladder cancer, confirming that it is a safe, feasible, economical and efficient model for selected patients, which can be promoted in suitable hospitals.

The mechanism of cilostazole alleviating intestinal mucosal barrier dysfunction in type 2 diabetic mice / 西安交通大学学报(医学版)

【Objective】 To explore the effect of cilostazol on intestinal barrier function in type 2 diabetes (T2DM). 【Methods】 The GSE142153 dataset was downloaded from GEO database to analyze gene changes in diabetic patients. Eight-week-old male db/db mice and control m/m mice were randomly divided into m/m+cmc, m/m+cilo, db/db+cmc, and db/db+cilo groups. Mice in different groups were given cilostazol and corresponding solvents for 4 weeks. We detected the levels of serum sCD40L and the expression of CD40 in intestinal tissue, and evaluated the mice’s intestinal barrier function by examining intestinal permeability, water content, bacterial number, and tight junction protein expression in different groups. 【Results】 Differential expressed genes were enriched in platelet activation and endothelial barrier function pathways in diabetic patients. Compared with those in the control group, the levels of serum sCD40L in db/db diabetic mice elevated significantly, and the CD40 expression, permeability, water content and bacterial number in intestinal tissue increased obviously, while the expression of tight junction protein decreased. Cilostazol treatment in diabetic mice decreased the levels of serum sCD40L and CD40, and alleviated significantly the intestinal barrier dysfunction. 【Conclusion】 Cilostazol attenuated the damage of intestinal barrier function in T2DM, and its protective effect may be related to the inhibition of platelet activation in diabetic mice.

KHK involved in intestinal barrier impairment by high-fat and high-fructose diet / 西安交通大学学报(医学版)

【Objective】 To explore the effect of high-fat and high-fructose diet on mouse intestinal barrier function, as well as the role of ketohexokinase (KHK), the key enzyme in fructose metabolism, in intestinal barrier impairment. 【Methods】 Eight-week-old male control C57BL/6J mice and Khk-/- mice were randomly divided into control + normal diet (ND), control + high-fat and high-fructose diet (HFHFD), Khk-/-+ normal diet (ND+Khk-/-), and Khk-/-+ high-fat and high-fructose diet (HFHFD+Khk-/-) groups, with eight mice in each group. During the high-fat and high-fructose diet and normal diet, the body weight changes of mice in different groups were recorded. After the intervention, the blood glucose and insulin levels of mice in each group were detected. The intestinal barrier function and inflammation level of mice were evaluated by detecting intestinal water content, permeability, tight junction protein expression, serum and intestinal inflammatory factor levels. 【Results】 Compared with ND group, HFHFD group significantly increased the body weight, blood glucose and insulin levels of mice, increased the intestinal water content and permeability, decreased the expression of tight junction proteins, and increased inflammatory factors of the serum and intestines. In the two groups fed with high-fat and high-fructose diet, the body weight, blood glucose and insulin levels of the HFHFD+Khk-/- group were significantly lower than those of HFHFD group, and the intestinal barrier dysfunction and inflammation were significantly improved. 【Conclusion】 KHK, a key enzyme in fructose metabolism, is involved in the impairment of intestinal barrier caused by high-fat and high-fructose diet. Knockout of Khk gene significantly improved intestinal barrier dysfunction and the inflammation level.