Effectiveness and prognosis of covered stents with different diameters in transjugular intrahepatic portosystemic shunt: a meta-analysis.

PURPOSE: This meta-analysis was designed to evaluate the clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) conducted utilizing stents of different diameters, thus providing recommendations for more logical selections of covered stents for patients with portal hypertension, in particular for the Asian population. MATERIALS AND METHODS: Web of Science, PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang were searched for randomized controlled trials and cohort studies from inception until February 2023. The meta-analysis was carried out using Revman 5.4 Software. Heterogeneity between researches was assessed by the χ2 test and I2 index. The outcomes evaluated were the incidence of post-TIPS hepatic encephalopathy (HE), variceal rebleeding, shunt dysfunction, 1-year overall survival and decrease in portal pressure gradient (PPG). RESULTS: Eight appropriate clinical trials with 1246 patients were selected (638 and 608 patients in the experimental and control groups, respectively). In regards to preoperative PPG reduction, there was no discernible difference between the two groups [mean difference = 1.15, 95% confidence interval (CI) = -0.29-2.58, P = 0.12]. The rate of post-TIPS HE was significantly higher in patients in the 8 mm stent group than in the 6-7 mm stent group [odds ratio (OR) = 0.54, 95% CI = 0.42-0.70, P < 0.00001, I2 = 46%]. There were no significant differences in the rates of variceal rebleeding (OR = 1.05, 95% CI = 0.67-1.65, P = 0.84, I2 = 0%), shunt dysfunction (OR = 0.88, 95% CI = 0.53-1.47, P = 0.64, I2 = 0%) and 1-year overall survival (OR = 0.86, 95% CI = 0.50-1.50, P = 0.61, I2 = 0%). CONCLUSION: Asian populations with portal hypertension may benefit more from TIPS with 6-7 mm covered stents because they can reduce the risk of postoperative HE while offering similar efficacy when compared to 8 mm covered stents.

Electroacupuncture pre-treatment alleviates sepsis-induced cardiac inflammation and dysfunction by inhibiting the calpain-2/STAT3 pathway.

Electroacupuncture (EA) has both anti-inflammatory and cardio-protective effects. Activation of calpain pathway is involved in several myocardiopathy. In sepsis, the role of calpain-2-regulated STAT3 in cardio-protective mechanism of electroacupuncture remains unclear. In this study, we aimed to elucidate the mechanism by which electroacupuncture reduces cardiac inflammation and apoptosis and improves cardiac function during sepsis. Electroacupuncture pretreatment for 7 days was applied in septic cardiomyopathy model induced by lipopolysaccharide (LPS). lipopolysaccharide-induced sepsis was associated with a dramatically systemic inflammation and cardiac dysfunction, which was alleviated by electroacupuncture pre-treatment. Lipopolysaccharide resulted in increases of pro-inflammatory factors (TNF-α,IL1ßand IL-6) and apoptosis (TUNEL staining and BAX/Bcl2) via activation of calpain-2/STAT3 pathway.Electroacupuncture pre-treatment inhibited LPS-induced activation of cardiac calpain-2/STAT3 signalling and ameliorated inflammatory and apoptosis. Additionally, inhibition of calpain-2 expression using the corresponding siRNA decreased the Phosphorylation of STAT3,pro-inflammatory factors and apoptosis in lipopolysaccharide- treated cardiomyocytes, confirming that calpain-2 activated p-STAT3 participate in septic cardiomyopathy. Furthermore, suppression of STAT3 by stattic enhanced anti-inflammatory and anti-apoptosis effects of electroacupuncture. These findings reveal mechanisms of electroacupuncture preconditioning protection against cardiac inflammation and apoptosis in sepsis mouse via calpain-2/STAT3 pathway and may provide novel targets for clinical treatments of the sepsis-induced cardiac dysfunction.

Catalpol as a Component of Rehmannia glutinosa Protects Spinal Cord Injury by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis.

Disturbance of the internal environment in the spinal cord after spinal cord injury (SCI) is an important cause of the massive death of neurons in the injury area and one of the major problems that lead to the difficult recovery of motor function in patients. Rehmannia glutinosa, a famous traditional Chinese medicine, is commonly used in neurodegenerative diseases, whereas an iridoid glycoside extract of catalpol (CAT), with antioxidant, antiapoptotic, and neuroprotective pharmacological effects. However, the neuroprotective and anti-apoptosis mechanism of CAT in SCI remains unclear. In our study, we found that CAT has a restorative effect on the lower limb motor function of rats with SCI by establishing a rat model of SCI and treating CAT gavage for 30 days. Our study further found that CAT has the effect of inhibiting apoptosis and protecting neurons, and the action pathway may reduce endoplasmic reticulum (ER) stress by inhibiting CHOP and GRP78 expression and then reduce apoptosis and protect neurons through the Caspase3/Bax/Bcl-2 pathway. In conclusion, we demonstrated that CAT can treat SCI by inhibiting ER stress-mediated neuronal apoptosis and has the potential to be a clinical drug for the treatment of SCI.

Ischemic stroke induces cardiac dysfunction and alters transcriptome profile in mice.

BACKGROUND: Stroke can induce cardiac dysfunction in the absence of primary cardiac disease; however, the mechanisms underlying the interaction between the neurological deficits and the heart are poorly understood. The objective of this study was to investigate the effects of stroke on cardiac function and to identify the transcriptome characteristics of the heart. RESULTS: Stroke significantly decreased heart weight/tibia length ratio and cardiomyocyte cross-sectional areas and increased atrogin-1 and the E3 ubiquitin ligase MuRF-1, indicating myocardial atrophy in MCAO-induced mouse hearts. RNA sequencing of mRNA revealed 383 differentially expressed genes (DEGs) in MCAO myocardium, of which 221 were downregulated and 162 upregulated. Grouping of DEGs based on biological function and quantitative PCR validation indicated that suppressed immune response and collagen synthesis and altered activity of oxidoreductase, peptidase, and endopeptidase may be involved in MCAO-induced cardiomyopathy. The DEGs were mainly distributed in the membrane or extracellular region of cardiomyocytes and acted as potential mediators of stroke-induced cardiac dysregulation involved in cardiac atrophy. CONCLUSION: Stroke induced a unique transcriptome response in the myocardium and resulted in immediate cardiac atrophy and dysfunction.

Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing.

OBJECTIVE: This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. METHOD: The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. RESULTS: ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. CONCLUSION: ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

Exercise in mice ameliorates high-fat diet-induced nonalcoholic fatty liver disease by lowering HMGCS2.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Exercise is a therapeutic strategy for preventing NAFLD. However, the underlying molecular mechanisms by which NAFLD can be ameliorated through exercise are still not clear. This study investigates the mechanisms by which exercise suppresses NAFLD development induced by a high-fat diet (HFD) in mice. Male 6-week-old C57BL/6J mice were fed a normal diet or HFD for 12 weeks and then induced to swim or remain sedentary for 8 weeks. Histomorphology, inflammatory factors, fat metabolizing enzymes, fibrosis, and steatosis were determined in HFD-fed mouse liver, and levels of hepatic enzymes and molecules in the related pathways were analyzed. NAFLD mice showed evident steatosis, fibrosis, and liver injury, and an increased expression of HMGCS2, Wnt3a/ ß-catenin, and phosphorylated (p)-AMPK in the liver. Exercise significantly attenuated these symptoms and downregulated the level of Wnt3a/ß-catenin in lipotoxic liver tissue. Inhibition of HMGCS2 expression decreased the activation of the Wnt3a/ß-catenin pathway and lowered p-AMPK in palmitate-treated HepG2. Our results suggest that exercise prevents NAFLD-associated liver injury, steatosis, and fibrosis. Exercise-mediated hepatoprotection was achieved partly via the blocking of the upregulation of HMGCS2 and the attenuation of the Wnt3a/ß-catenin pathway.

Exercise Training Reverses Lipotoxicity-induced Cardiomyopathy by Inhibiting HMGCS2.

PURPOSE: This study aimed to determine the effect of exercise training on preventing lipotoxic cardiomyopathy and to investigate the role of the 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) and miR-344g-5p in cardiomyocytes. METHODS: Male C57BL/6 mice were fed a 60% high-fat diet (HFD) for 12 wk then began swimming exercise or remained sedentary for 8 wk. Thereafter, cardiac function was assessed by echocardiography, and heart tissue and plasma were collected for further measurements. The molecular mechanism of exercise was investigated after treating Hmgcs2 siRNA in palmitate-induced neonatal mouse cardiomyocytes. RESULTS: HFD induced myocardial hypertrophy and fibrosis and reduced coronary reserve and cardiac function. HMGCS2 levels increased, but junctophilin-2 (JPH2) levels decreased in HFD mice hearts. Such effects were attenuated by swimming exercise. Mechanistically, Hmgcs2 silencing prevented apoptosis and caspase-3 cleavage and elevated the expression of JPH2 in palmitate-stimulated cardiomyocytes. In addition, exercise promoted miR-344g-5p expression in HFD hearts. The overexpression of miR-344g-5p by chemical mimic reduced HMGCS2, apoptosis, and caspase-3 cleavage and elevated JPH2 expression in palmitate-induced cardiomyocytes. CONCLUSION: Our results suggest that exercise limits lipid metabolic disorder, cardiac hypertrophy, and fibrosis and aids in the prevention of lipotoxic cardiomyopathy. Exercise-mediated cardioprotection by upregulating miR-344g-5p, which targets Hmgcs2 mRNA, prohibits HMGCS2 upregulation and thus lipotoxicity.

The Influence of AGEs Environment on Proliferation, Apoptosis, Homeostasis, and Endothelial Cell Differentiation of Human Adipose Stem Cells.

The aim of this study was to evaluate the changes of proliferation, apoptosis, homeostasis, and differentiation of human adipose-derived stem cells (hASCs) in the simulated diabetic microenvironment and discuss the potential of the mesenchymal stem cell in the treatment of chronic diabetic wound. We simulated diabetic microenvironment with glycation end products (AGEs) in vitro and studied the changes of hASCs in proliferation and apoptosis. We found that AGEs inhibited the proliferation and lead to hASCs apoptosis, and the endothelial cell directed differentiation was also inhibited. AGEs upregulated growth-related oncogene and monocyte chemoattractant protein-1 and downregulated urokinase-type plasminogen activator receptor, which may inhibit the proliferation and transference of endothelial cells. The simulated diabetic microenvironment affects the proliferation, apoptosis, and homeostasis of hASCs, the endothelial cell migration, and the synthesis of collagen protein, leading to delayed wound healing.

Wound Documentation by Using 3G Mobile as Acquisition Terminal: An Appropriate Proposal for Community Wound Care.

The increasing numbers of cases of wound disease are now posing a big challenge in China. For more convenience of wound patients, wound management in community health care centers under the supervision of a specialist at general hospitals is an ideal solution. To ensure an accurate diagnosis in community health clinics, it is important that "the same language" for wound description, which may be composed of unified format description, including wound image, must be achieved. We developed a wound information management system that was built up by acquisition terminal, wound description, data bank, and related software. In this system, a 3G mobile phone was applied as acquisition terminal, which could be used to access to the data bank. This documentation system was thought to be an appropriate proposal for community wound care because of its objectivity, uniformity, and facilitation. It also provides possibility for epidemiological study in the future.

[Advances in the research of treating refractory diabetic wounds with stem cells].

With the growth of aging society, China has become the country of population with the highest incidence of diabetes in the world. Diabetes leads to pathological changes in vascular and nervous system, rendering the diabetic skin fragile and hard to heal if wounded; in the end most diabetic wounds tend to become chronic skin ulcers. The refractory diabetic wound is the result of various endogenous and exogenous factors. It is a quite complicated pathophysiologic event which lacks an effective and specific therapeutic method in clinic. The use of stem cells could be a new approach of treating diabetic chronic wounds since they have a potential ability of self-renovation and multi-directional differentiation which will promote angiogenesis and wound healing process, thus be beneficial in the care of ischemia diseases of the lower limb. This article reviews basic theory of treating diabetic wound and the changes in microenvironment, and prompts many successful cases in curing refractory diabetic wounds.

[Research progress in treatment of bone defect with osteomyelitis by using drug-carried bionic nano-bone].

OBJECTIVE: To review the research progress in the treatment of bone defect or osteomyelitis with drug-carried bionic nano-bone so as to offer some theoretic supports and experimental references for those relative researchers. METHODS: The related literature was reviewed. The research progress in the treatment of bone defect or osteomyelitis with drug-carried bionic nano-bone was analyzed, which included the designing and preparing of drug-carried nano composites, the way of making infected bone defect animal models, and the general steps, test indexes and results. RESULTS: Traumatic osteomyelitis and bone defect were two kinds of disease to difficulty cure in nowadays clinical orthopaedics. The osteomyelitis, especially chronic one was quite troublesome during the treatments. Many researchers made artificial bone with nano-materials and added drugs into them by various ways for the purpose of controlling infection and repairing bone defection simultaneously. But these researches were still at the laboratory phase, lacking the criterions of making relative animal models, and needed to be improved in the way of drug slow-releasing and nano-scaffold producing. CONCLUSION: The drug-carried bionic nano-bone as a kind of newly emerging replacement material has splendid effects in the treatments of traumatic large area bone defect or osteomyelitis and will have a brilliant future.