Salvaging donated kidneys from prolonged warm ischemia during ex vivo hypothermic oxygenated perfusion.

Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide-releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.

Hypothermic machine perfusion reduces donation after circulatory death liver ischemia-reperfusion injury through the SERPINA3-mediated PI3Kδ/Akt pathway.

Hypothermic machine perfusion (HMP) has been demonstrated to be more effective in mitigating ischemia-reperfusion injury (IRI) of donation after circulatory death (DCD) organs than cold storage (CS), yet the underlying mechanism remains obscure. We aimed to propose a novel therapeutic approach to ameliorate IRI in DCD liver transplantation. Twelve clinical liver samples were randomly assigned to HMP or CS treatment and subsequent transcriptomics analysis was performed. By combining in vivo HMP models, we discovered that HMP attenuated inflammation, oxidative stress, and apoptosis in DCD liver through a SEPRINA3-mediated PI3Kδ/AKT signaling cascade. Moreover, in the hypoxia/reoxygenation (H/R) model of BRL-3A, overexpression of SERPINA3 mitigated H/R-induced apoptosis, while SERPINA3 knockdown exacerbated cell injury. Idelalisib (IDE) treatment also reversed the protective effect of SERPINA3 overexpression. Overall, our research provided new insights into therapeutic strategies and identified potential novel molecular targets for therapeutic intervention against DCD liver.

ALDH2 deficiency exacerbates MCD-diet induced MASLD by modulating bile acid metabolism.

Aldehyde dehydrogenase 2 (ALDH2), an acetaldehyde dehydrogenase in mitochondria, is primarily responsible for metabolizing alcohol-derived acetaldehyde and other endogenous aldehydes. Inactivating ALDH2 rs671 polymorphism is found in up to 8 % of the global population and 40 % of the East Asian population. Recent studies have shown that rs671 SNP mutation in the human ALDH2 gene is associated with an increased risk of metabolic dysfunction-associated steatotic liver diseases (MASLD), but the mechanism remains unclear. Here, we identify the role of ALDH2 in MASLD. Firstly, ALDH2 activity was lower in MASLD patients and the methionine-choline deficiency (MCD) diet induced MASLD model. Secondly, activation of ALDH2 activity with Alda-1 (ALDH2 agonist) attenuated MCD-diet induced hepatic triglyceride (TG) accumulation and steatosis, whereas the opposite result was observed with cyanamide (CYA, ALDH2 inhibitor). Furthermore, ALDH2 deficiency exacerbated hepatic steatosis, inflammation, and fibrosis in the MCD-diet induced mice. RNA sequencing (RNA-seq) revealed that oxysterol 7-α hydroxylase (Cyp7b1) and the related metabolic pathway significantly changed in the MCD-diet challenged ALDH2-/- mice. In ALDH2-/- mice, the expression of Cyp7b1 was downregulated and FXR/SHP signaling was inhibited, reducing the alternative bile acid (BA) synthetic pathway. In our in vitro experiments, knockdown of ALDH2 exacerbated TG accumulation in hepatocytes, whereas the opposite result was observed with overexpression of ALDH2. Moreover, chenodeoxycholic acid (CDCA) rescued ALDH2 downregulation induced TG accumulation in hepatocytes. Our study reveals that ALDH2 attenuates hepatocyte steatosis by regulating the alternative BA synthesis pathway, and ALDH2 may serve as a potential target for the treatment of MASLD.

New Drainage Management Following Liver Transplant Results in Fewer Postoperative Hospital Days.

OBJECTIVES: Drain tube management after liver transplant is controversial. A new peritoneal drainage management protocol was developed to validate clinical characteristics, such as drain characteristics, postoperative complications, duration of postoperative hospital stay, changes in albumin levels, and 30-day readmission rates. MATERIALS AND METHODS: Data from 183 consecutive patients who underwent deceased donor liver transplant at our institution between January 2019 and June 2022 were retrospectively analyzed. A new drain management protocol was implemented on August 1, 2021, which included early removal of the drain tube when the serum albumin level was >3 g/dL and nonchylous fluid drainage was <200 mL/day. RESULTS: When we compared the traditional and new drain management protocol groups (n = 131 vs n = 52), the new management protocol group showed a decrease in the median duration of intraperitoneal drainage. In addition, the median length of postoperative hospital stay decreased from 33 to 27 days and serum albumin levels returned to normal faster at postoperative 3 weeks. No significant differences were found in postoperative hemorrhage, hematoma, hydrops abdominis, infections, biliary complications, orin the rate ofreinterventions and 30-day rehospitalizations. CONCLUSIONS: The new management protocol was associated with fewer postoperative hospital days and faster recovery than traditional management. Our findings may aid in the development of new drain policy recommendations based on preexisting risk factors.

Association of baseline fasting plasma glucose with 1-year mortality in non-diabetic patients with acute cerebral infarction: a multicentre observational cohort study.

OBJECTIVES: Evidence on the association between fasting blood glucose and mortality in non-diabetic patients who had a stroke is limited. We aimed to investigate the association of baseline fasting plasma glucose (FPG) with 1 year all-cause mortality in non-diabetic patients with acute cerebral infarction (ACI). DESIGN: A multicentre prospective cohort study. SETTING: Four grade A tertiary hospitals in the Xi'an district of China. PARTICIPANTS: A total of 1496 non-diabetic patients within 7 days of ACI were included. MAIN OUTCOME MEASURES: The outcome was 1 year all-cause mortality. Baseline FPG was analysed as a continuous variable and was divided into four quartiles (group Q1-group Q4). We used multivariable Cox regression analyses, curve fitting and Kaplan-Meier (K-M) analyses to explore the association of baseline FPG with 1 year all-cause mortality in non-diabetic patients with ACI. RESULTS: After controlling for confounders, multivariable Cox regression analyses indicated a 17% increase in 1 year all-cause mortality for every 1 mmol/L of baseline FPG increase (HR=1.17, 95% CI 1.02 to 1.35, p=0.030). Patients from the Q4 group had 2.08 times increased hazard of 1 year all-cause mortality compared with the Q1 group (HR=2.08, 95% CI 1.13 to 3.82, p=0.019), while the survival rate of patients in group Q4 was decreased compared with that in other groups (p<0.001). The curve fitting revealed a positive but non-linear association of baseline FPG with 1-year all-cause mortality in non-diabetic patients with ACI. CONCLUSION: In non-diabetic patients with ACI, elevated baseline FPG is an independent risk factor for 1-year all-cause mortality, and the two are positively and non-linearly associated. These results suggest that high FPG should be seen as a concern in non-diabetic patients with ACI.

Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi'an Stroke Registry Study of China.

INTRODUCTION: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. METHODS: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. RESULTS: Among 2,288 participants, the mean TyG index was 8.8  0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98-2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09-7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. CONCLUSION: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients.

Pachymic acid protects hepatic cells against oxygen-glucose deprivation/reperfusion injury by activating sirtuin 1 to inhibit HMGB1 acetylation and inflammatory signaling.

Ischemia-reperfusion injury is an important cause of liver injury occurring during liver transplantation. It is usually caused by inflammatory response and oxidative stress-induced oxidative damage. Pachymic acid (PA) has various biological activities such as anti-inflammatory, antioxidant and anti-cancer. However, the action mechanism of PA in hepatic ischemia-reperfusion injury is currently unknown. In this study, liver cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate a hepatic ischemia-reperfusion injury model. The binding relationship between PA and sirtuin 1 (SIRT1) was analyzed by molecular docking. Cell viability was detected by Cell Counting Kit-8. Expression levels of SIRT1 and high mobility group box 1 (HMGB1) were detected by western blot. Subsequent levels of inflammatory factors were detected by related kits and western blot. Meanwhile, related kits were used to examine levels of oxidative stress markers including reactive oxygen species, malondialdehyde, superoxide dismutase and cytotoxicity-associated lactate dehydrogenase. Finally, cell apoptosis was detected by flow cytometry and western blot. The results showed that PA significantly ameliorated OGD/R-induced decrease in SIRT1 expression, increase in HMGB1 acetylation and HMGB1 translocation. Moreover, the elevated levels of inflammatory factors, oxidative stress indexes and cell apoptosis upon exposure to OGD/R were reversed by PA treatment. Moreover, the addition of SIRT1 agonist and inhibitor further demonstrated that PA exerted the aforementioned effects in OGD/R-exposed cells by targeting SIRT1. Thus, the present study revealed the mechanism by which PA ameliorated OGD/R-induced hepatic injury via SIRT1. These results might provide a clearer theoretical basis for the targeted treatment of OGD/R-induced hepatic injury with PA.

Elevated non-HDL-C/HDL-C ratio increases the 1-year risk of recurrent stroke in older patients with non-disabling ischemic cerebrovascular events: results from the Xi'an Stroke Registry Study of China.

BACKGROUND: Few studies have explored the prognostic role of nontraditional lipid-related indicators in non-disabling ischemic cerebrovascular events (NICE). In this study, we aimed to investigate the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and the1-year risk of recurrent stroke in patients with NICE. METHODS: Total cholesterol (TC), HDL-C, and patient information were collected at admission. Recurrent stroke events were followed up 3, 6, and 12 months after onset. Non-HDL-C levels were calculated by subtracting HDL-C from TC. The non-HDL-C/HDL-C ratio was treated as a continuous variable and in quartiles (Q1-Q4). Stratified multivariate Cox regression was used to investigate the relationship between the non-HDL-C/HDL-C ratio and the 1-year risk of recurrent stroke in patients with NICE. RESULTS: Overall, 1,659 patients with NICE were enrolled. For each unit increase in the non-HDL-C/HDL-C ratio, the 1-year risk of recurrent stroke in patients aged ≥ 65 years (older patients) with NICE increased by 64% in the adjusted model (hazard ratio [HR]: 1.64, 95%confidence interval [CI]:1.18-2.27, P = 0.003), and the HRs were 3.21 and 4.24 times higher in the Q3 and Q4 groups than that in the Q1 group, which was considered to be the reference (adjusted model Q3: HR: 3.21, 95%CI: 1.05-9.83, P = 0.041; adjusted model Q4: HR: 4.24, 95%CI: 1.30-13.85, P = 0.017). However, there was no significant difference in patients younger than 65 years. Both curve fitting and Kaplan-Meier cumulative risk analysis showed that an elevated non-HDL-C/HDL-C ratio significantly increased the 1-year risk of recurrent stroke in older patients with NICE. The optimal range for the non-HDL-C/HDL-C ratio should be no higher than the Q2 group (2.256-2.939). Stratified Cox regression analysis showed that these results tended to be stable for different comorbidities (all P for interaction > 0.05). CONCLUSIONS: Elevated non-HDL-C/HDL-C ratios significantly increased the 1-year risk of recurrent stroke in older patients with NICE. Therefore, clinicians need to pay more attention to this indicator when managing older patients with NICE.

Hypothermic oxygenated perfusion attenuates DCD liver ischemia-reperfusion injury by activating the JAK2/STAT3/HAX1 pathway to regulate endoplasmic reticulum stress.

BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) in donation after cardiac death (DCD) donors is a major determinant of transplantation success. Endoplasmic reticulum (ER) stress plays a key role in hepatic IRI, with potential involvement of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and the antiapoptotic protein hematopoietic-lineage substrate-1-associated protein X-1 (HAX1). In this study, we aimed to investigate the effects of hypothermic oxygenated perfusion (HOPE), an organ preservation modality, on ER stress and apoptosis during hepatic IRI in a DCD rat model. METHODS: To investigate whether HOPE could improve IRI in DCD livers, levels of different related proteins were examined by western blotting and quantitative real-time polymerase chain reaction. Further expression analyses, immunohistochemical analyses, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and transmission electron microscopy were conducted to analyze the effects of HOPE on ER stress and apoptosis. To clarify the role of the JAK2/STAT3 pathway and HAX1 in this process, AG490 inhibitor, JAX1 plasmid transfection, co-immunoprecipitation (CO-IP), and flow cytometry analyses were conducted. RESULTS: HOPE reduced liver injury and inflammation while alleviating ER stress and apoptosis in the DCD rat model. Mechanistically, HOPE inhibited unfolded protein responses by activating the JAK2/STAT3 pathway, thus reducing ER stress and apoptosis. Moreover, the activated JAK2/STAT3 pathway upregulated HAX1, promoting the interaction between HAX1 and SERCA2b to maintain ER calcium homeostasis. Upregulated HAX1 also modulated ER stress and apoptosis by inhibiting the inositol-requiring enzyme 1 (IRE1) pathway. CONCLUSIONS: JAK2/STAT3-mediated upregulation of HAX1 during HOPE alleviates hepatic ER stress and apoptosis, indicating the JAK2/STAT3/HAX1 pathway as a potential target for IRI management during DCD liver transplantation.

Plasma lncRNA LIPCAR Expression Levels Associated with Neurological Impairment and Stroke Subtypes in Patients with Acute Cerebral Infarction: A Prospective Observational Study with a Control Group.

INTRODUCTION: This prospective observational study with a control group aimed to compare the plasma levels of long non-coding RNA (lncRNA) LIPCAR between patients with acute cerebral infarction (ACI) and healthy controls, and to assess the prognostic abilities of LIPCAR for adverse outcomes of patients with ACI at 1-year follow-up. METHODS: Eighty patients with ACI, of whom 40 had large artery atherosclerosis (LAA) and 40 had cardioembolism (CE) and who were hospitalized at Xi'an No. 1 Hospital from July 2019 to June 2020, were selected as the case group. Age- and sex-matched non-stroke patients from the same hospital throughout the same time period were chosen as the control group. Real-time quantitative reverse transcription polymerase chain reaction was used to measure the levels of plasma lncRNA LIPCAR. The correlations of LIPCAR expression among the LAA, CE, and control groups were assessed using Spearman's correlation analysis. Curve fitting and multivariate logistic regression were used to analyze the LIPCAR levels and 1-year adverse outcomes of patients with ACI and its subtypes. RESULTS: The expression of plasma LIPCAR in the case group was noticeably higher than that of the control group (2.42 ± 1.49 vs. 1.00 ± 0.47, p < 0.001). Patients with CE had considerably higher levels of LIPCAR expression than those with LAA. The National Institute of Health Stroke Scale score and modified Rankin scale score on admission were significantly positively correlated with LIPCAR expression in patients with CE and LAA. Furthermore, the correlation was stronger in patients with CE than in those with LAA, with correlation coefficients of 0.69 and 0.64, respectively. Curve fitting revealed a non-linear correlation between LIPCAR expression levels, 1-year recurrent stroke, all-cause mortalities, and poor prognoses, with a cut-off value of 2.2. CONCLUSION: The expression level of lncRNA LIPCAR may play a potential role in the identification of neurological impairment and CE subtype in patients with ACI. Increased 1-year risk of adverse outcomes may be associated with high levels of LIPCAR expression.

Acute cerebral infarction is the second-leading cause of death worldwide. Therefore, available diagnostic and prognostic tools are of the utmost importance. It is easy to acquire hematologic biomarkers and to provide direct information related to the severity of brain injury and the risk of stroke. However, it has been shown that the study of hematologic markers in aspects of both identifying stroke subtypes and predicting neurological impairment are still few and imperfect in clinical application of stroke prognosis. The long non-coding RNA LIPCAR plays an important role in the pathophysiology of cardiovascular disease. Nonetheless, to date, no exploration has been carried out on the correlation between lncRNA LIPCAR, severity on admission, and prognosis of stroke subtypes. Thus, this study aimed to investigate the plasma levels of lncRNA LIPCAR expression and their correlations in patients with acute cerebral infarction and its subtypes. Our results show that the plasma levels of LIPCAR expression of the patients with acute cerebral infarction were noticeably higher than those of the non-stroke control patients. Patients with cardioembolism subtype had considerably higher levels of LIPCAR expression than those with large artery atherosclerosis. The National Institute of Health Stroke Scale score and modified Rankin scale score on admission were significantly correlated with LIPCAR expression in patients with cardioembolism and large artery atherosclerosis; the correlation was stronger in patients with cardioembolism than in patients with large artery atherosclerosis, with correlation coefficients of 0.69 and 0.64, respectively. Furthermore, curve fitting revealed a non-linear correlation between LIPCAR expression levels and 1-year outcome events. The expression level of lncRNA LIPCAR may play a potential role in the identification of neurological impairment and cardioembolism subtype in patients with acute cerebral infarction.

Serum homocysteine level is an independent risk factor for 1-year stroke recurrence in patients with acute ischemic stroke and H-type hypertension: results from the Xi'an stroke registry study of China.

Background: H-type hypertension has a high prevalence in China. However, the association of serum homocysteine levels with 1-year stroke recurrence in patients with acute ischemic stroke (AIS) and H-type hypertension has not been studied. Methods: A prospective cohort study of patients with AIS admitted to hospitals between January and December 2015 in Xi'an, China, was conducted. Serum homocysteine levels, demographic data, and other relevant information were collected from all patients upon admission. Stroke recurrences were routinely tracked at 1, 3, 6, and 12 months after discharge. The blood homocysteine level was studied as a continuous variable and tertiles (T1-T3). A multivariable Cox proportional hazard model and a two-piecewise linear regression model were utilized to evaluate the association and ascertain the threshold effect regarding the serum homocysteine level and 1-year stroke recurrence in patients with AIS and H-type hypertension. Results: Overall, 951 patients with AIS and H-type hypertension were enrolled, of whom 61.1% were male. After adjusting for confounders, patients in T3 had a significantly increased risk of recurrent stroke within 1 year, compared with those in T1 as the reference (hazard ratio = 2.24, 95% confidence interval: 1.01-4.97, p = 0.047). Curve fitting showed that serum homocysteine levels were positively curvilinearly correlated with 1-year stroke recurrence. Threshold effect analysis showed that an optimal threshold of serum homocysteine level <25 µmol/L was effective in reducing the risk of 1-year stroke recurrence in patients with AIS and H-type hypertension. Elevated homocysteine levels in patients with severe neurological deficits on admission significantly increased the risk of 1-year stroke recurrence (p for interaction = 0.041). Conclusions: In patients with AIS and H-type hypertension, the serum homocysteine level was an independent risk factor for 1-year stroke recurrence. A serum homocysteine level of ≥25 µmol/L significantly increased the risk of 1-year stroke recurrence. These findings can inform the creation of a more precise homocysteine reference range for the prevention and treatment of 1-year stroke recurrence in patients with AIS and H-type hypertension and provide a theoretical foundation for the individualized prevention and treatment of stroke recurrence.

Study on the law of initial gas expansion energy and its feasibility in coal and gas outburst prediction.

In order to explore the relationship between IEERG and outburst intensity and verify the feasibility of the former in predicting coal and gas outburst, a series tests with different gases and different gas pressures were conducted on the basis of self-developed coal and gas outburst simulation system and IEERG measuring instrument. The results show that with the increase of gas pressure, the IEERG increases gradually. Under the same gas pressure, the coal has the strongest adsorption capacity for CO2, followed by CH4 and N2. When the IEERG is less than 24.40 mJ·g-1, no outburst will occur. When the IEERG is greater than 24.40 mJ·g-1, weak outburst will occur. When the IEERG is greater than 34.72 mJ·g-1, strong outburst will occur. This shows that the magnitude of IEERG is closely related to the outburst. The larger the IEERG, the greater the possibility of outburst and the greater the intensity of outburst. It is feasible to predict the risk of outburst using IEERG, and it can be quantified.

A novel ameliorated rat model of reversible obstructive jaundice. / ä¸€ç§æ–°åž‹æ”¹è‰¯å¼å¯é€†æ€§æ¢—é˜»æ€§é»„ç–¸å¤§é¼ æ¨¡åž‹çš„å»ºç«‹.

Obstructive jaundice is a common clinical symptom generally caused by bile duct stones, inflammatory hyperplasia, and tumors. It is characterized by hyperbilirubinemia and may trigger a variety of complications such as hypotension, kidney injury, endotoxemia, multiple organ dysfunction syndrome, and even death (Pavlidis and Pavlidis, 2018; Liu et al., 2021). Relieving bile duct obstruction and providing adequate drainage have been considered as the most effective therapies for obstructive jaundice. However, it has not yet been established whether it is beneficial to treat affected patients by pre-operative biliary drainage (Blacker et al., 2021). Moreover, the pathophysiological changes or mechanisms associated with the reversal of organ function following the relief of bile-duct obstruction are unclear (Huang et al., 2004). Therefore, it is necessary to establish an experimental model of reversible obstructive jaundice to simulate biliary drainage in clinical practice.

Factors influencing the success of cryopreserved parathyroid autotransplantation: A systematic review.

Permanent hypoparathyroidism is a postoperative complication of thyroid and parathyroid surgery and can be cured by cryopreserved parathyroid autotransplantation (CPAT). However, due to the lack of unified and standardized guidelines, the limited ability of the parathyroid tissue itself to withstand cryopreservation, and some yet-to-be-defined processes or technologies, the success rate of cryopreserved parathyroid autotransplantation varies between institutions; it is low for some institutions and high for others. Due to the sparsity of data, views vary on which factors most influence the success rate of cryopreserved parathyroid autotransplantation. In this review, we analyzed the following probable influencing factors: ischemic period before cryopreservation; processes of cryopreservation and thawing, including freezing medium; freezing and thawing methods; duration of cryopreservation; examination of the graft before transplantation; graft site; mass of transplanted tissue fragments; blood calcium level; and the evaluation criteria for cryopreserved parathyroid autotransplantation success. Although the effects of these factors are debatable, we hypothesized that examining them in the above-given order to determine whether they affect the success rate of cryopreserved parathyroid autotransplantation could be beneficial to maximizing the success rate. Our findings led us to conclude that cryopreserved parathyroid autotransplantation operations should be standardized. Standardized guidelines for cryopreserved parathyroid autotransplantation that include such factors as ischemic period time, freezing and thawing methods, and recipient status should be established based on a comprehensive analysis of these factors.

Aldehyde Dehydrogenase 2 Protects the Kidney from Ischemia-Reperfusion Injury by Suppressing the IκBα/NF-κB/IL-17C Pathway.

Objective: Ischemia-reperfusion injury (IRI) is an important cause of delayed functional recovery after transplantation. This study is aimed at investigating the molecular mechanism of ALDH2 in a kidney ischemia-reperfusion model based on RNA-seq. Methods: We performed kidney ischemia-reperfusion in ALDH2-/- and WT mice and evaluated kidney function and morphology using SCr, HE staining, TUNEL staining, and TEM. We used RNA-seq to compare mRNA expression in ALDH2-/- and WT mice after IR, and then, we verified the related molecular pathways by PCR and western blotting. In addition, activators and inhibitors of ALDH2 were used to alter the activity of ALDH2. Finally, we established a model of hypoxia and reoxygenation in HK-2 cells and clarified the role of ALDH2 in IR by interfering with ALDH2 and using an NF-κB inhibitor. Results: After kidney ischemia-reperfusion, the SCr value increased significantly, kidney tubular epithelial cells were damaged, and the apoptosis rate increased. In the microstructure, mitochondria were swollen and deformed, and ALDH2 deficiency aggravated these changes. The NF-κB pathway and IL-17 pathway were significantly enriched in ALDH2-/- mice compared with WT mice according to KEGG enrichment analysis of the RNA-seq data. The PCR results showed that the mRNA expression levels of IκBα and IL-17B, C, D, E, and F were significantly higher than those in the WT-IR group. Western blot verification results showed that ALHD2 knockdown resulted in increased phosphorylation of IκBα, increased phosphorylation of NF-κB, and increased expression of IL-17C. When we used ALDH2 agonists, the number of lesions and the expression levels of the corresponding proteins were reduced. Knockdown of ALDH2 in HK-2 cells resulted in a higher proportion of apoptotic cells after hypoxia and reoxygenation, but inhibiting the phosphorylation of NF-κB prevented the increase in apoptosis and reduced the protein expression level of IL-17C. Conclusion: ALDH2 deficiency can lead to the aggravation of kidney ischemia-reperfusion injury. RNA-seq analysis and validation by PCR and western blotting revealed that this effect may be due to the promotion of IκBα/NF-κB p65 phosphorylation during ischemia-reperfusion caused by ALDH2 deficiency, which then leads to an increase in inflammatory factors, including IL-17C. Thus, cell death is promoted, and kidney IRI is eventually aggravated. We link ALDH2 deficiency with inflammation, revealing a new idea for ALDH2-related research.

Effect of Matrix Metalloproteinase 23 Accelerating Wound Healing Induced by Hydroxybutyl Chitosan.

Skin wounds may cause severe financial and social burden due to the difficulties in wound healing. Original inert dressings cannot meet multiple needs in the process of wound healing. Therefore, the development of materials to accelerate healing progress is essential and urgent. In the previous study, we found that the homogeneously synthesized hydroxybutyl chitosan (HBCS) had an effective performance in promoting wound healing. Proteomic analysis of the same specimen suggested that matrix metalloproteinase 23 (MMP23) may play a key role in HBCS expediting the progress of wound healing. In this work, we aim to reveal the underlying mechanism of MMP23 in the dynamic process of cutaneous proliferation and repair period. In order to regulate the expression level of MMP23 in the local wound area, we leaded in adeno-associated virus (AAV) to specifically decreased expression quantity of MMP23 in rat skin. In contrast to the negative control groups, we found that the wound closed faster and the collagen fibers and neovascularization were significantly increased in AAV groups. These findings highlighted that MMP23 was involved in wound healing after traumatic injury, and managing the expression of MMP23 could be a potential intervention target to accelerate wound healing.

Biocompatible and biodegradable chitin-based hydrogels crosslinked by BDDE with excellent mechanical properties for effective prevention of postoperative peritoneal adhesion.

Postoperative peritoneal adhesions are common complications caused by abdominal and pelvic surgery, which seriously impact the quality of life of patients and impose additional financial burdens. Using of biomedical materials as physical barriers to completely isolate the traumatic organ and injured tissue is an optimal strategy for preventing postoperative adhesions. However, the limited efficacy and difficulties in the complete degradation or integration of biomedical materials with living tissues restrict the application of these materials. In this study, novel chitin-based crosslinked hydrogels with appropriate mechanical properties and flexibilities were developed using a facile and green strategy. The developed hydrogels simultaneously exhibited excellent biocompatibilities and resistance to nonspecific protein adsorption and NIH/3T3 fibroblast adhesion. Furthermore, these hydrogels were biodegradable and could be completely integrated into the native extracellular matrix. The chitin-based crosslinked hydrogels also effectively inhibited postoperative peritoneal adhesions in rat models of adhesion and recurrence. Therefore, these novel chitin-based crosslinked hydrogels are excellent candidate physical barriers for the efficient prevention of postoperative peritoneal adhesions and provide a new anti-adhesion strategy for biomedical applications.

Non-Linear Association Between Serum Alkaline Phosphatase and 3-Month Outcomes in Patients With Acute Stroke: Results From the Xi'an Stroke Registry Study of China.

Background: Alkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China. Methods: We enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1-Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3-6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes. Results: Overall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19-3.96; P = 0.011] and patients in Q3 (76.8-92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14-0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0-76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes (P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia (P > 0.05) for all outcomes. Conclusion: Non-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges.

Mild hypothermia ameliorates hepatic ischemia reperfusion injury by inducing RBM3 expression.

Liver ischemia reperfusion injury (IRI) is a serious complication of certain liver surgeries, and it is difficult to prevent. As a potential drug-free treatment, mild hypothermia has been shown to promote positive outcomes in patients with IRI. However, the protective mechanism remains unclear. We established in vivo and in vitro models of hepatic ischemia reperfusion (IR) and mild hypothermia pretreatment. Hepatocytes were transfected with RNA-binding motif protein 3 (RBM3) overexpression plasmids, and IR was performed. Cell, culture medium, blood and tissue samples were collected to assess hepatic injury, oxidative stress, apoptosis and changes in RBM3 expression in the liver. Upregulation of RBM3 expression by mild hypothermia reduced the aminotransferase release, liver tissue injury and mitochondrial injury induced by liver IR. Hepatic IR-induced p38 and c-Jun N-terminal kinase (JNK) signaling pathway activation, oxidative stress injury and apoptosis could be greatly reversed by mild hypothermia. Overexpression of RBM3 mimicked the hepatoprotective effect of mild hypothermia. Mild hypothermia protects the liver from ischemia reperfusion-induced p38 and JNK signaling pathway activation, oxidative stress injury and apoptosis through the upregulation of RBM3 expression.

Relationship between serum alkaline phosphatase and poor 3-month prognosis in acute ischemic stroke patients with preserved renal function: results from Xi'an Stroke Registry Study of China.

BACKGROUND: In recent years, alkaline phosphatase (ALP) has been considered as one of the independent risk factors of acute ischemic stroke (AIS) and leads to worse clinical outcomes in patients with renal failure. In this study, we aim to investigate whether serum ALP level is associated with poor early-term prognosis in relationship of AIS patients with preserved renal function. METHODS: A prospectively collected database of AIS patients hospitalized in the Xi'an district of China from January to December, 2015 was analyzed. The demographics, serum ALP levels and stroke outcomes of all patients at 3 months were reviewed. Patients were routinely followed-up for 3 months. Serum ALP level was analyzed as a continuous variable and quintiles (Q1-Q5). Multivariate logistic regression model and a two-piecewise linear regression model were used to investigate the relationship and to determine the threshold effect regarding serum ALP levels and poor 3-month prognosis of AIS patients with preserved renal function. RESULTS: Overall, 1922 AIS patients were enrolled with 62.3% of them being men. The risk of having a poor 3-month prognosis was significantly increased in Q1, Q2, Q3 and Q5, when compared to that in Q4 being as the reference. The highest risk was noted in Q5 (odds ratio 2.21, 95% confidence interval: 1.32-3.73, P = 0.003) after being adjusted for confounders. Further analysis revealed a J-shaped curvilinear relationship between ALP levels and a poor 3-month prognosis of strokes (optimal threshold ALP level = 90 U/L). The relationship between both parameters was not significantly affected by age, sex, drinking, hypertension and leukocyte count (stratified by 10 × 109/L) (P for interaction > 0.05). CONCLUSIONS: Serum ALP was noted as an independent risk factor for a poor 3-month prognosis of AIS patients with preserved renal function. ALP levels higher than 90 U/L could cause an increased risk of a poor 3-month prognosis.