Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

The effects of music therapy on peripherally inserted central catheter in hospitalized children with leukemia.

To explore the effect of music therapy on children with leukemia who have peripherally inserted central catheters (PICC).In this study, we divided 107 patients undergoing PICC into music group (47 cases) and control group (60 cases). The music group received music therapy during PICC, while the control group was given no complementary treatment. The total length of catheterization, the use of sedatives and the changes of pain level and emotion level before and after PICC placement were compared between two groups.Compared with the control group, the total PICC placement time of the music group was significantly shorter (35(30-40) vs. 60(60-60); Z = -8.307; p < 0.001), and the use of sedative medications was also significantly reduced (4.35% (n = 2) vs. 91.84% (n = 45); p < 0.001). Moreover, the pain of catheterization was significantly alleviated. The median difference of pain scores of the music group was significantly less (2(1-3) vs. 5(5-5); p < 0.001). The mood of patients was also improved. The median difference of emotional scores of the music group was significantly more (5(4.75-6) vs. 3(3-3); p < 0.001) than the control group.Music therapy is effective to use in PICC. It can shorten the treatment time, reduce the use of sedative medications, and improve the children's emotion and pain response significantly, which is worth clinical application.

Ultrasonic/CT image fusion guidance facilitating percutaneous catheter drainage in treatment of acute pancreatitis complicated with infected walled-off necrosis.

BACKGROUND: As the firs-line treatment for acute pancreatitis (AP) related infectious walled-off necrosis (WON), percutaneous catheter drainage (PCD) are usually accomplished under CT or US guidance, either of which has certain disadvantages. It is necessary to verify the clinical effects of using US and CT images fusion as guidance of PCD. METHODS: The total 94 consecutive AP patients with infected WON from January of 2013 to January of 2017 were included. Among these patients with infected WON, 48 received PCD under simple US guidance (US-PCD) and 46 under US/CT images fusion guidance (US/CT-PCD). The clinical data consisting of puncture data, drainage effectiveness indicators, intervention complications were collected. RESULTS: The demographic characteristics and disease related characteristics of two groups were comparable. After 48 h of PCD treatment, the US/CT-PCD group achieved a significantly higher imaging effective rate, and significantly lower inflammatory response indexes and severity score, than the US-PCD group (P < 0.05). The US/CT-PCD group required fewer puncture times and drainage tubes and lower rate of advanced treatment, showing higher operational success rate than the US-PCD group (P < 0.05). Moreover, the US/CT-PCD group exhibited significantly fewer puncture related complications, lower hospital stay, intubation time, and hospitalization expenses than the US-PCD group (P < 0.05). CONCLUSION: PCD treatment under the US/CT images fusion guidance is a reliable intervention with definite clinical effects for AP complicated with infected WON.

[Effects of Yinzhihuang oral liquid and Lonicera japonica extract on hemolysis and hyperbilirubinemia in rats with glucose-6-phosphate dehydrogenase deficiency].

OBJECTIVE: To investigate the effects of different doses of Yinzhihuang oral liquid and different concentrations of Lonicera japonica extract on hemolysis and hyperbilirubinemia in rats with glucose-6-phosphate dehydrogenase (G6PD) deficiency. METHODS: Male Wistar rats were randomly divided into 10 groups (n=10 each): normal control group (untreated), negative control group (saline-treated), positive control group (primaquine-treated), low-, medium- and high-dose Yinzhihuang oral liquid groups (13.4, 26.8, and 53.6 mL/kg, respectively), and low-, medium-, high-, and very-high-concentration Lonicera japonica groups (6.7 mL/kg administered, containing 8, 40, 80, and 160 mg/mL Lonicera japonica extract, respectively). A rat model of acetylphenylhydrazine-induced G6PD deficiency was established in all groups except the normal control group, as confirmed by the morphological changes in erythrocytes observed using Wright's stain. After treatment, routine blood and biochemical tests were conducted to measure hemolytic indices, as well as changes in total and indirect bilirubin levels. RESULTS: Rats with G6PD deficiency demonstrated irregular erythrocytes with a lighter-staining center. In the positive control group, the red blood cell count decreased, while the free hemoglobin count and the reticulocyte percentage increased, as compared with before treatment (P<0.05); in all the Yinzhihuang oral liquid groups and Lonicera japonica extract groups, all the above indices except reticulocyte percentage returned to the levels before treatment (P<0.05). Compared with the positive control group, all the Yinzhihuang oral liquid groups had significantly reduced total and indirect bilirubin levels (P<0.05), and all the Lonicera japonica group had significantly reduced indirect bilirubin levels (P<0.05). However, the total bilirubin level was significantly higher in the Lonicera japonica groups than in the Yinzhihuang oral liquid groups (P<0.05). The low-dose Yinzhihuang oral liquid group demonstrated a significantly greater decrease in total bilirubin level than the medium- and high-dose Yinzhihuang oral liquid group (P<0.05). CONCLUSIONS: Administration of high-dose Yinzhihuang oral liquid and different concentrations of Lonicera Japonica extract do not cause hemolysis in rats with G6PD deficiency. Yinzhihuang oral liquid is more effective in treating hyperbilirubinemia than Lonicera Japonica extract. However, the efficacy of Yinzhihuang oral liquid may not be dose-dependent.

[Effect of rhubarb on neonatal rats with bronchopulmonary dysplasia induced by hyperoxia].

OBJECTIVE: To study the effect of rhubarb on neonatal rats with bronchopulmonary dysplasia (BPD) induced by hyperoxia. METHODS: A total of 64 rats (postnatal day 4) were randomly divided into four groups: air control, rhubarb control, hyperoxia model, and hyperoxia+rhubarb (n=16 each). The rats in the hyperoxia model and hyperoxia+rhubarb groups were exposed to hyperoxia (60% O2) to establish a BPD model. The rats in the rhubarb control and hyperoxia+rhubarb groups were given rhubarb extract suspension (600 mg/kg) by gavage daily. The pathological changes of lung tissue were evaluated by hematoxylin-eosin staining on postnatal days 14 and 21. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by spectrophotometry. The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined by RT-PCR and Western blot respectively. RESULTS: The hyperoxia model group showed reduced alveolar number, increased alveolar volume, and simplified alveolar structure, which worsened over the time of exposure to hyperoxia. These pathological changes were significantly reduced in the hyperoxia+rhubarb group. On postnatal days 14 and 21, compared with the air control and rhubarb control groups, the hyperoxia model group had significantly reduced radical alveolar count (RAC), significantly reduced activity of SOD in the lung tissue, and significantly increased content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P<0.05). Compared with the hyperoxia model group, the hyperoxia+rhubarb group had significantly increased RAC, significantly increased activity of SOD in the lung tissue, and significantly reduced content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P<0.05). CONCLUSIONS: Rhubarb may play a protective role in rats with BPD induced by hyperoxia through inhibiting inflammatory response and oxidative stress.

The Role of Exogenous Hydrogen Sulfide in Free Fatty Acids Induced Inflammation in Macrophages.

BACKGROUND: This study aimed to investigate whether exogenous hydrogen sulfide (H2S) can protect the RAW264.7 macrophages against the inflammation induced by free fatty acids (FFA) by blunting NLRP3 inflammasome activation via a specific TLR4/NF-κB pathway. METHODS: RAW264.7 macrophages were exposed to increasing concentrations of FFA for up to 3 days to induce FFA-induced inflammation. The cells were pretreated with NaHS (a donor of H2S) before exposure to FFA. Cell viability, cell apoptosis, TLR4, NF-κB, NLRP3 inflammasome, IL-1ß, IL-18 and cleaved caspase-3 expression were measured by a combination of MTT assay, ELISA, and immunoblotting. RESULTS: H2S attenuated FFA-induced cell apoptosis, and reduced the expression of NLRP3, ASC, pro-caspase-1, caspase-1, IL- 1ß, IL-18 and caspase-3. In addition, H2S inhibited the FFA-induced activation of TLR4 and NF-κB. Furthermore, NLRP3 inflammasome activation was regulated by the TLR4 and NF-κB pathway. CONCLUSION: The present study demonstrated for the first time that H2S appears to suppress FFA-induced macrophage inflammation and apoptosis by inhibiting the TLR4/ NF-κB pathway and its downstream NLRP3 inflammasome activation. Thus H2S might possess potential in the treatment of diseases resulting from FFA overload like insulin resistance and type diabetes.

[A comparative analysis of neonatal critical illness score and score for neonatal acute physiology, perinatal extension, version II].

OBJECTIVE: To investigate the accuracy and clinical utility of neonatal critical illness score (NCIS) and score for neonatal acute physiology, perinatal extension, version II (SNAPPE-II) in predicting the "dead and abandoned" risk in critically ill neonates. METHODS: A total of 269 critically ill neonates were divided into two groups according to their prognosis: dead/abandoned and improved/cured. The accuracy of these two scoring systems, NCIS and SNAPPE-II, in predicting the "dead and abandoned" risk was compared. RESULTS: The dead/abandoned group had a significantly higher SNAPPE-II score than the improved/cured group (P<0.001), while there was no significant difference in the NCIS score between the two groups (P=0.091). The children who were in line with the individual indicator in the NCIS results had a significantly higher "dead and abandoned" risk than those who were not (P=0.005). CONCLUSIONS: SNAPPE-II is more accurate in early prediction of the "dead and abandoned" risk in critically ill neonates compared with NCIS. NCIS has the ability to predict the "dead and abandoned" risk in children in line with the individual indicator.

A Simple Fluorescence Probe Based on Aggregation-Induced Emission (AIE) Property for the Detection of Mg(2+) Ions.

A simple aggregation-induced emission-based fluorescence probe (1) for Mg(2+) was synthesized by condensation of benzene-1, 2-diamine with 5-bromo-2-hydroxybenzaldehyde, This compound shows favourable character of the AIE-active molecules. More importantly, after addition of Mg(2+) to probe (1) in acetonitrile, the solution changed from colorless to yellow colour solution under ultraviolet (UV) radiation obtained from hand-held UV lamp, this finding suggested that probe (1) can be used to detect Mg(2+) by colorimetric detection. Detection limit can reach 2.31 × 10(-5) M(-1). The practical value of the selective and sensitive fluorescence indicators was confirmed by its application to detection of magnesium ion in acetonitrile.

What is the impact of n-3 PUFAs on inflammation markers in Type 2 diabetic mellitus populations?: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To explore the possible role of n-3 polyunsaturated fatty acids (PUFAs) in lowering inflammation markers in individuals with type 2 diabetes mellitus. METHODS: PubMed, CNKI and Cochrane databases were searched until December 30, 2015; references from papers or reviews were also retrieved and screened. Screening was performed by two independent researchers, and randomized controlled trials reporting the specific n-3 PUFA type, dose, frequency, and duration of treatment, as well as the baseline and follow-up concentrations of inflammation markers, including interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP), were selected for final analysis. Data analysis was performed using RevMan 5.2 software. RESULTS: Eight studies involving 955 participants were included; all reported CRP. Only one included study reported IL-2 or IL-6 while two studies reported TNF-α. N-3 PUFAs significantly reduced CRP concentration compared with control [SMD 95 % CI, 1.90 (0.64, 3.16), Z = 2.96, P = 0.003, random effect model]. CONCLUSIONS: N-3 PUFAs decrease CRP concentration in type-2 diabetes mellitus. However, larger and rigorously designed RCTs are required to confirm this finding and extend it into other inflammatory biomarkers.

Outcome benefit of abdominal paracentesis drainage for severe acute pancreatitis patients with serum triglyceride elevation by decreasing serum lipid metabolites.

BACKGROUND: Our previous reports demonstrated that abdominal paracentesis drainage (APD) exerts a beneficial effect on severe acute pancreatitis (SAP) patients. However, the underlying mechanisms for this effectiveness are not well understood. METHODS: A retrospective cohort of 132 consecutive non-hypertriglyceridemia (HTG)-induced SAP patients with triglyceride (TG) elevation and pancreatitis-associated ascitic fluid (PAAF) was recruited from May 2010 to May 2015 and included in this study. The patients were divided into two groups: the APD group (n = 68) and the non-APD group (n = 64). The monitored parameters mainly included mortality, hospital stay, the incidence of further intervention, levels of serum lipid metabolites and inflammatory factors, parameters related to organ failure and infections, and severity scores. RESULTS: The demographic data and severity scores were comparable between the two groups. Compared with the non-APD group, the primary outcomes (including mortality, hospital stay and the incidence of percutaneous catheter drainage) in the APD group were improved. The serum levels of lipid metabolites were significantly lower in the APD group after 2 weeks of treatment than in the non-APD group. Logistic regression analysis indicated that the decreased extent of free fatty acid (FFA)(odds ratio, 1.435; P = 0.015) was a predictor of clinical improvement after 2 weeks of treatment. CONCLUSION: Treatment with APD benefits non-HTG-induced SAP patients with serum TG elevation by decreasing serum levels of FFA.

The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases.

Mesenchymal stem cells (MSCs) are a group of stem cells derived from the mesodermal mesenchyme. MSCs can be obtained from a variety of tissues, including bone marrow, umbilical cord tissue, umbilical cord blood, peripheral blood and adipose tissue. Under certain conditions, MSCs can differentiate into many cell types both in vitro and in vivo, including hepatocytes. To date, four main strategies have been developed to induce the transdifferentiation of MSCs into hepatocytes: addition of chemical compounds and cytokines, genetic modification, adjustment of the micro-environment and alteration of the physical parameters used for culturing MSCs. Although the phenomenon of transdifferentiation of MSCs into hepatocytes has been described, the detailed mechanism is far from clear. Generally, the mechanism is a cascade reaction whereby stimulating factors activate cellular signalling pathways, which in turn promote the production of transcription factors, leading to hepatic gene expression. Because MSCs can give rise to hepatocytes, they are promising to be used as a new treatment for liver dysfunction or as a bridge to liver transplantation. Numerous studies have confirmed the therapeutic effects of MSCs on hepatic fibrosis, cirrhosis and other liver diseases, which may be related to the differentiation of MSCs into functional hepatocytes. In addition to transdifferentiation into hepatocytes, when MSCs are used to treat liver disease, they may also inhibit hepatocellular apoptosis and secrete various bioactive molecules to promote liver regeneration. In this review, the capacity and molecular mechanism of MSC transdifferentiation, and the therapeutic effects of MSCs on liver diseases are thoroughly discussed.

Abdominal paracentesis drainage ahead of percutaneous catheter drainage benefits patients attacked by acute pancreatitis with fluid collections: a retrospective clinical cohort study.

OBJECTIVE: The efficacy and safety of ultrasound-guided abdominal paracentesis drainage ahead of percutaneous catheter drainage as the new second step of a step-up approach are evaluated. DESIGN: The observed parameters were compared between groups including mortality, infection, organ failure, inflammatory factor levels, indexes of further interventions, and drainage-related complications. PATIENTS: This retrospective study included 102 consecutive patients with acute pancreatitis from June 2009 to June 2011. INTERVENTIONS: In this step-up approach, all patients subsequently received medical management, percutaneous catheter drainage (with or without previous abdominal paracentesis drainage), and necrosectomy if necessary according to indications. The patients were divided into two groups: 53 cases underwent abdominal paracentesis drainage followed by percutaneous catheter drainage (abdominal paracentesis drainage + percutaneous catheter drainage group) and 49 cases were managed only with percutaneous catheter drainage (percutaneous catheter drainage-alone group). MEASUREMENTS AND MAIN RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the abdominal paracentesis drainage + percutaneous catheter drainage group (0%) than the percutaneous catheter drainage-alone group (8.2%) (p = 0.050). Compared with the percutaneous catheter drainage-alone group, the laboratory variables of the abdominal paracentesis drainage + percutaneous catheter drainage group decreased more rapidly, the mean number of failed organs was lower, and the interval from the onset of disease to further interventions was much longer. However, there was no significant difference in the prevalence and duration of infections between the two groups. CONCLUSION: Application of abdominal paracentesis drainage ahead of percutaneous catheter drainage is safe and beneficial to patients by reducing inflammatory factors, postponing further interventions, and delaying or avoiding multiple organ failure.

Effect of percutaneous catheter drainage on pancreatic injury in rats with severe acute pancreatitis induced by sodium taurocholate.

OBJECTIVE: This study investigated the effect of percutaneous catheter drainage (PCD) on pancreatic injury in severe acute pancreatitis (SAP) rats. METHODS: Sixty Wistar rats were equally randomized into three groups: a sham operated control group, an SAP control group, and a PCD group. The levels of inflammatory cytokines, the activity of group II phospholipase A2 (PLA2) in blood and ascitic fluid, and the pancreas level of group II PLA2 and trypsin activity were measured 24 h after the operation. The apoptosis of the pancreatic cells, the expression of cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), active caspase-3, Bcl-2 and Bax in the pancreas was detected. Pancreatic pathological changes were observed. RESULTS: The levels of proinflammatory cytokines, the activity of group II PLA2 and trypsin activity in pancreas in the SAP group were higher than those in the PCD group. The histopathological results revealed that the pancreatic injury was alleviated in the PCD group. The expression of COX-2 and iNOS in the pancreatic tissue in the SAP control rats was higher than that in the PCD rats. The expression of Bcl-2 was decreased and the expression of active caspase-3 and Bax was increased in the pancreas of PCD rats. The apoptosis index of the pancreatic cells in the PCD rats was higher than that in the SAP control rats. CONCLUSION: PCD can relieve SAP-induced pancreatic injury by inhibiting inflammatory reactions, and promoting apoptosis of pancreatic cells.

Hydrogen-rich saline protects against ischemia/reperfusion injury in grafts after pancreas transplantations by reducing oxidative stress in rats.

PURPOSE: This study aimed to investigate the therapeutic potential of hydrogen-rich saline on pancreatic ischemia/reperfusion (I/R) injury in rats. METHODS: Eighty heterotopic pancreas transplantations (HPT) were performed in syngenic rats. The receptors were randomized blindly into the following three groups: the HPT group and two groups that underwent transplantation and administration of hydrogen-rich saline (HS, >0.6 mM, 6 mL/kg) or normal saline (NS, 6 mL/kg) via the tail vein at the beginning of reperfusion (HPT + HS group, HPT + NS group). Samples from the pancreas and blood were taken at 12 hours after reperfusion. The protective effects of hydrogen-rich saline against I/R injury were evaluated by determining the changes in histopathology and measuring serological parameters, oxidative stress-associated molecules, and proinflammatory cytokines. RESULTS: Administration of hydrogen-rich saline produced notable protection against pancreatic I/R injury in rats. Histopathological improvements and recovery of impaired pancreatic function were observed. In addition, TNF-α, IL-1ß, and IL-6 were reduced markedly in the HPT + HS group. Additionally, there were noticeable inhibitory effects on the pancreatic malondialdehyde level and considerable recruitment of SOD and GPx, which are antioxidants. CONCLUSION: Hydrogen-rich saline treatment significantly attenuated the severity of pancreatic I/R injury in rats, possibly by reducing oxidative stress and inflammation.

Unbalanced distribution of materials: the art of giving rise to hepatocytes from liver stem/progenitor cells.

Liver stem/progenitor cells (LSPCs) are able to duplicate themselves and differentiate into each type of cells in the liver, including mature hepatocytes and cholangiocytes. Understanding how to accurately control the hepatic differentiation of LSPCs is a challenge in many fields from preclinical to clinical treatments. This review summarizes the recent advances made to control the hepatic differentiation of LSPCs over the last few decades. The hepatic differentiation of LSPCs is a gradual process consisting of three main steps: initiation, progression and accomplishment. The unbalanced distribution of the affecting materials in each step results in the hepatic maturation of LSPCs. As the innovative and creative works for generating hepatocytes with full functions from LSPCs are gradually accumulated, LSPC therapies will soon be a new choice for treating liver diseases.

Notch inhibition promotes fetal liver stem/progenitor cells differentiation into hepatocytes via the inhibition of HNF-1ß.

In a previous study, the Notch pathway inhibited with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (also called DAPT) was shown to promote the differentiation of fetal liver stem/progenitor cells (FLSPCs) into hepatocytes and to impair cholangiocyte differentiation. The precise mechanism for this, however, was not elucidated. Two mechanisms are possible: Notch inhibition might directly up-regulate hepatocyte differentiation via HGF (hepatocyte growth factor) and HNF (hepatocyte nuclear factor)-4α or might impair cholangiocyte differentiation thereby indirectly rendering hepatocyte differentiation as the dominant state. In this study, HGF and HNF expression was detected after the Notch pathway was inhibited. Although our initial investigation indicated that the inhibition of Notch induced hepatocyte differentiation with an efficiency similar to the induction via HGF, the results of this study demonstrate that Notch inhibition does not induce significant up-regulation of HGF or HNF-4α in FLSPCs. This suggests that Notch inhibition induces hepatocyte differentiation without the influence of HGF or HNF-4α. Moreover, significant down-regulation of HNF-1ß was observed, presumably dependent on an impairment of cholangiocyte differentiation. To confirm this presumption, HNF-1ß was blocked in FLSPCs and was followed by hepatocyte differentiation. The expression of markers of mature cholangiocyte was impaired and hepatocyte markers were elevated significantly. The data thus demonstrate that the inhibition of cholangiocyte differentiation spontaneously induces hepatocyte differentiation and further suggest that hepatocyte differentiation from FLSPCs occurs at the expense of the impairment of cholangiocyte differentiation, probably being enhanced partially via HNF-1ß down-regulation or Notch inhibition.

Effects of treatment with hydrogen sulfide on methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats.

BACKGROUND AND AIM: Oxidative stress and inflammation play important roles in the progression from simple fatty liver to non-alcoholic steatohepatitis (NASH). The aim of this work was to investigate whether treatment with hydrogen sulfide (H2 S) prevented NASH in rats through abating oxidative stress and suppressing inflammation. METHODS: A methionine-choline-deficient (MCD) diet rat model was prepared. Rats were divided into three experimental groups and fed for 8 weeks as follows: (i) control rats; (ii) MCD-diet-fed rats; (iii) MCD-diet-fed rats treated with NaHS (intraperitoneal injection of 0.1 mL/kg/day of 0.28 mol/L NaHS, a donor of H2 S). RESULTS: MCD diet impaired hepatic H2 S biosynthesis in rats. Treatment with H2 S prevented MCD-diet-induced NASH, as evidenced by hematoxylin and eosin staining, reduced apoptosis and activities of alanine aminotransferase and aspartate aminotransferase, and attenuated hepatic fat accumulation in rats. Treatment with H2 S abated MCD-diet-induced oxidative stress through reducing cytochrome p4502E1 expression, enhancing heme oxygenase-1 expression, and suppressing mitochondrial reactive oxygen species formation, and suppressed MCD-diet-induced inflammation through suppressing activated nuclear factor κB signaling and reducing interleukin-6 and tumor necrosis factor α expressions. In addition, treatment of MCD-diet fed rats with H2 S had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers. CONCLUSIONS: Treatment with H2 S prevented NASH induced by MCD diet in rats possibly through abating oxidative stress and suppressing inflammation.

Ultrasound-guided double-tract percutaneous cholecystostomy combined with a choledochoscope for performing cholecystolithotomies in high-risk surgical patients.

BACKGROUND: Cholecystolithiasis is the most common disease treated by general surgery, with an incidence of about 0.15-0.22%. The most common therapies are open cholecystectomy (OC) or laparoscopic cholecystectomy (LC). However, with a greater understanding of the function of the cholecyst, more and more patients and surgeons are aware that preserving the functional cholecyst is important for young patients, as well as patients who would not tolerate anesthesia associated with either OC or LC. Based on these considerations, we have introduced a notable, minimally invasive treatment for cholecystolithotomy. METHODS: We performed a retrospective review of patients with cholecystolithiasis who were unable to tolerate surgery or who insisted on preserving the functional cholecyst. Our particular approach can be simply described as ultrasound-guided percutaneous cholecystostomy combined with a choledochoscope for performing a cholecystolithotomy under local anesthesia. RESULTS: Ten patients with cholecystolithiasis were treated via this approach. All except one patient had their gallbladder stones totally removed under local anesthesia, without the aggressive procedures associated with OC or LC. The maximum number of gallbladder stones removed was 16, and the maximum diameter was 13 mm without lithotripsy. After the minimally invasive surgery, the cholecyst contractile functions of all patients were normal, confirmed via ultrasound after a high-fat diet. Complications such as bile duct injury, biliary fistula, and bleeding occurred significantly less often than with OC and LC. The recurrence rates for each of 2 post-operative years were about 11.11% (1/9, excluding a failure case) with uncertainty surrounding recurrence or residue, and 22.22% (2/9, including one non-recurrence patient with follow-up time of 22 months), respectively. CONCLUSIONS: Ultrasound-guided percutaneous cholecystostomy combined with choledochoscope is a safe, efficient, and minimally invasive cholecystolithotomy method. We recommend this technique for the management of small stones (less than 15 mm) in high-risk surgical patients.

Therapeutic effect and mechanism of electroacupuncture at Zusanli on plasticity of interstitial cells of Cajal: a study of rat ileum.

BACKGROUND: Electroacupuncture (EA) is one of the techniques of acupuncture and is believed to be an effective alternative and complementary treatment in many disorders. The aims of this study were to investigate the effects and mechanisms of EA at acupoint Zusanli (ST36) on the plasticity of interstitial cells of Cajal (ICCs) in partial bowel obstruction. METHODS: A Sprague Dawley rat model of partial bowel obstruction was established and EA was conducted at Zusanli (ST36) and Yinglingquan (SP9) in test and control groups, respectively. Experiments were performed to study the effects and mechanisms of EA at Zusanli on intestinal myoelectric activity, distribution and alteration of ICCs, expression of inflammatory mediators, and c-Kit expression. RESULTS: 1) EA at Zusanli somewhat improved slow wave amplitude and frequency in the partial obstruction rats. 2) EA at Zusanli significantly stimulated the recovery of ICC networks and numbers. 3) the pro-inflammatory mediator TNF-α and NO activity were significantly reduced after EA at Zusanli, However, no significant changes were observed in the anti-inflammatory mediator IL-10 activity. 4) EA at Zusanli re-expressed c-Kit protein. However, EA at the control acupoint, SP9, significantly improved slow wave frequency and amplitude, but had no effect on ICC or inflammatory mediators. CONCLUSIONS: We concluded that EA at Zusanli might have a therapeutic effect on ICC plasticity, and that this effect might be mediated via a decrease in pro-inflammatory mediators and through the c-Kit signaling pathway, but that the relationship between EA at different acupoints and myoelectric activity needs further study.

Robust Graphene-based Aerogel for Integrated 3D Asymmetric Supercapacitors with High Energy Density.

Three-dimensional asymmetric supercapacitors (3D ASC) have garnered significant attention due to their high operating window, theoretical energy density, and circularity. However, the practical application of 3D electrode materials is limited by brittleness and excessive dead volume. Therefore, we propose a controlled contraction strategy that regulates the pore structure of 3D electrode materials, eliminates dead volume in the 3D skeleton structure, and enhances mechanical strength. In this study to obtain reduced graphene oxide/manganese dioxide (rGO/MnO2) and reduced graphene oxide/carbon nanotube (rGO/CNT) composite aerogels with a stable and compact structure. MnO2 and CNT as nanogaskets, preventing the self-stacking of graphene nanosheets during the shrinkage process. Additionally, the high specific capacitor nanogaskets significantly enhance the specific energy density of the rGO aerogel electrode. The prepared rGO/MnO2//rGO/CNT 3D ASC exhibits a high mass-specific capacitance of 216.15 F g-1, a high mass energy density of 74 Wh kg-1 at 3.5 A g-1, and maintains a retention rate of capacitance at 99.89 % after undergoing 10,000 cycles of charge and discharge at 5 A g-1. The versatile and integrated assembly of 3D ASC units is achieved through the utilization of the robust mechanical structure of rGO-based aerogel electrodes, employing a mortise and tenon structural design.