Cell size and xylem differentiation regulating genes from Salicornia europaea contribute to plant salt tolerance.

Cell wall is involved in plant growth and plays pivotal roles in plant adaptation to environmental stresses. Cell wall remodelling may be crucial to salt adaptation in the euhalophyte Salicornia europaea. However, the mechanism underlying this process is still unclear. Here, full-length transcriptome indicated cell wall-related genes were comprehensively regulated under salinity. The morphology and cell wall components in S. europaea shoot were largely modified under salinity. Through the weighted gene co-expression network analysis, SeXTH2 encoding xyloglucan endotransglucosylase/hydrolases, and two SeLACs encoding laccases were focused. Meanwhile, SeEXPB was focused according to expansin activity and the expression profiling. Function analysis in Arabidopsis validated the functions of these genes in enhancing salt tolerance. SeXTH2 and SeEXPB overexpression led to larger cells and leaves with hemicellulose and pectin content alteration. SeLAC1 and SeLAC2 overexpression led to more xylem vessels, increased secondary cell wall thickness and lignin content. Notably, SeXTH2 transgenic rice exhibited enhanced salt tolerance and higher grain yield. Altogether, these genes may function in the succulence and lignification process in S. europaea. This work throws light on the regulatory mechanism of cell wall remodelling in S. europaea under salinity and provides potential strategies for improving crop salt tolerance and yields.

Ginsenoside Rg1 promotes fetal hemoglobin production in vitro: A potential therapeutic avenue for ß-thalassemia.

ß-thalassemia, a globally prevalent genetic disorder, urgently requires innovative treatment options. Fetal hemoglobin (HbF) induction stands as a key therapeutic approach. This investigation focused on Ginsenoside Rg1 from the Panax genus for HbF induction. Employing K562 cells and human erythroid precursor cells (ErPCs) derived from neonatal cord blood, the study tested Rg1 at different concentrations. We measured its effects on γ-globin mRNA levels and HbF expression, alongside assessments of cell proliferation and differentiation. In K562 cells, Rg1 at 400 µM significantly increased γ-globin mRNA expression by 4.24 ± 1.08-fold compared to the control. In ErPCs, the 800 µM concentration was most effective, leading to an over 80% increase in F-cells and a marked upregulation in HbF expression. Notably, Rg1 did not adversely affect cell proliferation or differentiation, with the 200 µM concentration showing an increase in γ-globin mRNA by 2.33 ± 0.58-fold, and the 800 µM concentration enhancing HbF expression by 2.59 ± 0.03-fold in K562 cells. Our results underscore Rg1's potential as an effective and safer alternative for ß-thalassemia treatment. By significantly enhancing HbF levels without cytotoxicity, Rg1 offers a notable advantage over traditional treatments like Hydroxyurea. While promising, these in vitro findings warrant further in vivo exploration to confirm Rg1's therapeutic efficacy and to unravel its underlying mechanistic pathways.

Computerised modified paramedian approach technique versus conventional midline approach technique of lumbar puncture: a randomised control trial protocol.

INTRODUCTION: The lumbar puncture (LP) technique is widely used for diagnostic and therapeutic purposes. In recent years, the paramedian approach technique (PAT) has gained increasing interest due to its advantages over the conventional midline approach technique (MAT) that has been traditionally employed in clinical practice for LP. However, there have been inconsistent discussions regarding the efficacy of different LP techniques. Based on digital virtual human and computer simulation techniques, a new approach called computerised modified PAT (CMPAT) was proposed. Therefore, the aim of this study is to discuss a randomised controlled trial (RCT) protocol to investigate and compare the effects of CMPAT and MAT in patients undergoing LP. METHODS AND ANALYSIS: We will conduct a prospective, multicentre RCT. The study will recruit 84 patients aged 18-99 years who require LP. Participants will be randomly assigned to either the CMPAT treatment group (group A) or the MAT treatment group (group B). The primary outcome measure will be the number of needle insertion attempts required for a successful LP. Secondary outcomes will include the puncture success rate, pain assessment in the back, head, and legs, and the occurrence of complications. The measurement of these secondary outcomes will be taken during the procedure, as well as at specific time points: 30 min, 6 hours, 1 day, 3 days, 7 days, 2 weeks and 4 weeks after the procedure. Pain levels will be assessed using a Numerical Rating Scale. ETHICS AND DISSEMINATION: Ethical approval (2022YF052-01) has been obtained from the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China. The research findings will be published in an international peer-reviewed scientific journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300067937.

Inhibiting the m6A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.

Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown. Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition. Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression. Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.

GANT61, an inhibitor of Gli1, inhibits the proliferation and migration of hepatocellular carcinoma cells.

Constitutive activation of Hedgehog (Hh) signaling has been implicated in many cancers including hepatocellular carcinoma (HCC). Among them, the terminal glioma-associated oncogene homolog 1 (Gli1) regulates the expression of critical genes in the Hh pathway. The current study aims to evaluate the anti-HCC effect of the Gli1 inhibitor, GANT61. In vitro analysis including cell counting kit-8 (CCK-8) assay, flow cytometry, and migration and invasion assay were adopted to evaluate the effect of GANT61 on HCC cell lines. In vivo, xenograft studies were also performed to verify the effect of GANT61 on HCC. By CCK-8 assay, we found that GANT61 could significantly reduce the growth of HCC cell lines Huh7 and hemophagocytic lymphohistiocytosis (HLE), and their IC50 concentrations were 4.481 and 6.734 µM, respectively. Flow cytometry shows that GANT61 induced cell cycle arrest in the G2/M phase and accelerated apoptosis of both HLE and Huh7 cells. While migration and invasion assay shows that GANT61 weakens cells' migration and invasion ability. Besides that, GANT61 inhibits the expression of Gli1, FoxM1, CyclinD1, and Bcl-2, upregulates the level of Bax protein, and also reverses the epithelial-mesenchymal transition program by downregulating the expression of Vimentin and N-Cadherin and upregulating the expression of epithelial E-Cadherin expression. Furthermore, GANT61 inhibits the growth of subcutaneous xenografts of Huh7 cells in nude mice. Overall, this study suggests that Gli1 is a potential target for therapy and GANT61 shows promising therapeutic potential for future treatment in HCC.

PHT1;5 Repressed by ANT Mediates Pi Acquisition and Distribution under Low Pi and Salinity in Salt Cress.

Salinity and phosphate (Pi) starvation are the most common abiotic stresses that threaten crop productivity. Salt cress (Eutrema salsugineum) displays good tolerance to both salinity and Pi limitation. Previously, we found several Phosphate Transporter (PHT) genes in salt cress upregulated under salinity. Here, EsPHT1;5 induced by both low Pi (LP) and salinity was further characterized. Overexpression of EsPHT1;5 in salt cress enhanced plant tolerance to LP and salinity, while the knock-down lines exhibited growth retardation. The analysis of phosphorus (P) content and shoot/root ratio of total P in EsPHT1;5-overexpressing salt cress seedlings and the knock-down lines as well as arsenate uptake assays suggested the role of EsPHT1;5 in Pi acquisition and root-shoot translocation under Pi limitation. In addition, overexpression of EsPHT1;5 driven by the native promoter in salt cress enhanced Pi mobilization from rosettes to siliques upon a long-term salt treatment. Particularly, the promoter of EsPHT1;5 outperformed that of AtPHT1;5 in driving gene expression under salinity. We further identified a transcription factor EsANT, which negatively regulated EsPHT1;5 expression and plant tolerance to LP and salinity. Taken together, EsPHT1;5 plays an integral role in Pi acquisition and distribution in plant response to LP and salt stress. Further, EsANT may be involved in the cross-talk between Pi starvation and salinity signaling pathways. This work provides further insight into the mechanism underlying high P use efficiency in salt cress in its natural habitat, and evidence for a link between Pi and salt signaling.

Endowing the Operability of Supercapacitors at High Temperatures by Regulating the Solvation Structure in Dilute Hybrid Electrolyte with Trimethyl Phosphate Cosolvent.

The redox stabilities of different oxygen donor solvents (C═O, P═O and S═O) and lithium salt anions for supercapacitors (SCs) electrolytes have been compared by calculating the frontier molecular orbital energy. Among six lithium difluoro(oxalate)borate (LiDFOB)-based mono-solvent electrolytes, the dilute LiDFOB-1,4-butyrolactone (GBL) electrolyte exhibits the highest operating voltage but suffers from electrolyte breakdown at elevated temperatures. Trimethyl phosphate (TMP) exhibits the highest redox stability and a strongly negative electrostatic potential (ESP), making it suitable for promoting the dissolution of LiDFOB as expected. Therefore, TMP is selected as a co-solvent into LiDFOB-GBL electrolyte to regulate Li+ solvation structure and improve the operability of electrolytes at high temperatures. The electrochemical stable potential window (ESPW) of 0.5 m LiDFOB-G/T(5/5) hybrid electrolyte can reach 5.230 V. The activated carbon (AC)-based symmetric SC using 0.5 m LiDFOB-G/T(5/5) hybrid electrolyte achieves a high energy density of 54.2 Wh kg-1 at 1.35 kW kg-1 and the capacitance retention reaches 89.2% after 10 000 cycles. The operating voltage of SC can be maintained above 2 V when the temperature rises to 60 °C.

Active control on topological interface states of elastic wave metamaterials with double coupled chains.

Topological elastic wave metamaterials have shown significant advantages in manipulating wave propagation and realizing localized modes. However, topological properties of most mechanical metamaterials are difficult to change because of structural limitations. This work proposes the elastic wave metamaterials with double coupled chains and active control, in which band inversion and topological interface modes can be achieved by flexibly tuning negative capacitance circuits. Finite element simulations and experiments are performed to demonstrate the topological interface modes, which show good agreements with the theoretical results. This research seeks to provide effective strategies for the design and application of topological elastic wave metamaterials.

[Mechanism of stress-induced microglial activation in depression and traditional Chinese medicine regulation].

Depression exists with high prevalence and heavy disease burden. Stress events play a key role in the occurrence of depression, but the pathological mechanism has not been fully clarified by reason of the complexity and heterogeneity. In recent years, neuroinflammation as a pathological mechanism of depression has received extensive attention. The activated microglia is regarded as the marker of neuroinflammation, which is an important link of stress-induced depression. Stress might induce microglia activation through pattern recognition receptors(PRR), intestinal flora, hypothalamic-pituitary-adrenal(HPA) axis, and other pathways. Cross-talk between impaired microglia function and neurobiological factors such as inflammatory cytokines, serotonin metabolism, and neuroplasticity may lead to depression. At present, a large number of studies have proved that traditional Chinese medicine(TCM) plays an anti-depressive role by inhibiting microglia activation, which may be potential treatment strategies for depressive disorder. This paper reviewed the research progress of stress-induced microglia activation in depression and summarized the mechanism of TCM against depression with regard to microglia, hoping to provide experimental evidence and consideration for TCM against depression through microglia.

Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy.

BACKGROUND: Fibroblast growth factor (FGF) 15/19, which is expressed in and secreted from the distal ileum, can regulate hepatic glucose metabolism in an endocrine manner. The levels of both bile acids (BAs) and FGF15/19 are elevated after bariatric surgery. However, it is unclear whether the increase in FGF15/19 is induced by BAs. Moreover, it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery. AIM: To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy (SG). METHODS: By calculating and comparing the changes of body weight after SG with SHAM group, we examined the weight-loss effect of SG. The oral glucose tolerance test (OGTT) test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG. By detecting the glycogen content, expression and activity of glycogen synthase as well as the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (Pepck), we evaluated the hepatic glycogen content and gluconeogenesis activity. We examined the levels of total BA (TBA) together with the farnesoid X receptor (FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery. Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4 (FGFR4) with its corresponding signal pathways involved in glucose metabolism were detected. RESULTS: After surgery, food intake and body weight gain of SG group was decreased compare with the SHAM group. The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG, while the expression of the key enzyme for hepatic gluconeogenesis: G6Pase and Pepck, were depressed. TBA levels in serum and portal vein were both elevated after SG, the FXR-agonistic BA subspecies: Chenodeoxycholic acid (CDCA), lithocholic acid (LCA) in serum and CDCA, DCA, LCA in portal vein were all higher in SG group than that in SHAM group. Consequently, the ileal expression of FXR and FGF15 were also advanced in SG group. Moreover, the hepatic expression of FGFR4 was stimulated in SG-operated rats. As a result, the activity of its corresponding pathway for glycogen synthesis: FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated, while the corresponding pathway for hepatic gluconeogenesis: FGFR4- cAMP regulatory element-binding protein- peroxisome proliferator-activated receptor γ coactivator-1α pathway was suppressed. CONCLUSION: Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR. Furthermore, the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Role of Mutations of Mitochondrial Aminoacyl-tRNA Synthetases Genes on Epileptogenesis.

Mitochondria are the structures in cells that are responsible for producing energy. They contain a specific translation unit for synthesizing mitochondria-encoded respiratory chain components: the mitochondrial DNA (mt DNA). Recently, a growing number of syndromes associated with the dysfunction of mt DNA translation have been reported. However, the functions of these diseases still need to be precise and thus attract much attention. Mitochondrial tRNAs (mt tRNAs) are encoded by mt DNA; they are the primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. Previous research has shown the role of mt tRNAs in the epileptic mechanism. This review will focus on the function of mt tRNA and the role of mitochondrial aminoacyl-tRNA synthetase (mt aaRS) in order to summarize some common relevant mutant genes of mt aaRS that cause epilepsy and the specific symptoms of the disease they cause.

Clinical effect and follow-up of laparoscopic radical proximal gastrectomy for upper gastric carcinoma.

Objective: To evaluate the safety and clinical effect of tubular esophagogastric anastomosis in laparoscopic radical proximal gastrectomy. Methods: A retrospective analysis was conducted involving 191 patients who underwent laparoscopic radical proximal gastrectomy in the Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University from January 2017 to October 2020. Patients were divided into tubular esophagogastric anastomosis group (TG group) and traditional esophagogastric anastomosis group (EG group) according to the digestive tract reconstruction. Their intraoperative conditions, perioperative recovery and postoperative follow-up were compared. Patients were also divided into indocyanine green group and non-indocyanine green group according to whether or not indocyanine green tracer technology was used during the operation. Their intraoperative condition and perioperative recovery were compared and analyzed after propensity score matching. Results: The operation was successfully completed in all patients. Compared with the EG group, the TG group had less volume of gastric tube drainage, shorter gastric tube drainage time and proton pump inhibitors application time, and lower reuse rate of proton pump inhibitors. However, the TG group had a higher anastomotic stenosis at three months after surgery, as measured using anastomotic width and dysphagia score. Nevertheless, the incidence of reflux esophagitis and postoperative quality of life score in the TG group were lower compared with the EG group at 1st and 2nd year after surgery. In the indocyanine green analysis, the indocyanine green group had significantly shorter total operation time and lymph node dissection time and less intraoperative blood loss compared with the non-indocyanine green group. However, compared with the non-indocyanine green group, more postoperative lymph nodes were obtained in the indocyanine green group. Conclusion: Laparoscopic radical proximal gastrectomy is safe and effective treatment option for upper gastric cancer. Tubular esophagogastric anastomosis has more advantages in restoring postoperative gastrointestinal function and reducing reflux, but it has a higher incidence of postoperative anastomotic stenosis compared with traditional esophagogastrostomy. The application of indocyanine green tracer technique in laparoscopic radical proximal gastrectomy has positive significance.

Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?

More and more clinical trials have explored the role of liquid biopsy in the diagnosis and treatment of EGFR-mutated NSCLC. In certain circumstances, liquid biopsy has unique advantages and offers a new way to detect therapeutic targets, analyze drug resistance mechanisms in advanced patients, and monitor MRD in patients with operable NSCLC. Although its potential cannot be ignored, more evidence is needed to support the transition from the research stage to clinical application. We reviewed the latest progress in research on the efficacy and resistance mechanisms of targeted therapy for advanced NSCLC patients with plasma ctDNA EGFR mutation and the evaluation of MRD based on ctDNA detection in perioperative and follow-up monitoring.

MicroRNA-7a-5p ameliorates diabetic peripheral neuropathy by regulating VDAC1/JNK/c-JUN pathway.

AIMS: The pathogenesis of diabetic peripheral neuropathy (DPN) is complex, and its treatment is extremely challenging. MicroRNA-7a-5p (miR-7a-5p) has been widely reported to alleviate apoptosis and oxidative stress in various diseases. This study aimed to investigate the mechanism of miR-7a-5p in DPN. METHODS: DPN cell model was constructed with high-glucose-induced RSC96 cells. Cell apoptosis and viability were detected by flow cytometry analysis and cell counting kit-8 (CCK-8) assay respectively. The apoptosis and Jun N-terminal kinase (JNK)/c-JUN signalling pathway-related proteins expression were detected by Western blotting. The intracellular calcium content and oxidative stress levels were detected by flow cytometry and reagent kits. Mitochondrial membrane potential was evaluated by tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) staining. The targeting relationship between miR-7a-5p and voltage-dependent anion-selective channel protein 1 (VDAC1) was determined by RNA pull-down assay and dual-luciferase reporter gene assay. The streptozotocin (STZ) rat model was constructed to simulate DPN in vivo. The paw withdrawal mechanical threshold (PTW) was measured by Frey capillary line, and the motor nerve conduction velocity (MNCV) was measured by electromyography. RESULTS: MiR-7a-5p expression was decreased, while VDAC1 expression was increased in HG-induced RSC96 cells and STZ rats. In HG-induced RSC96 cells, miR-7a-5p overexpression promoted cell proliferation, inhibited apoptosis, down-regulated calcium release, improved mitochondrial membrane potential and repressed oxidative stress response. MiR-7a-5p negatively regulated VDAC1 expression. VDAC1 knockdown improved cell proliferation activity, suppressed cell apoptosis and mitochondrial dysfunction by inhibiting JNK/c-JUN pathway activation. MiR-7a-5p overexpression raised PTW, restored MNCV and reduced oxidative stress levels and nerve cell apoptosis in STZ rats. CONCLUSION: MiR-7a-5p overexpression ameliorated mitochondrial dysfunction and inhibited apoptosis in DPN by regulating VDAC1/JNK/c-JUN pathway.

The m6A reader YTHDC2 promotes SIRT3 expression by reducing the stabilization of KDM5B to improve mitochondrial metabolic reprogramming in diabetic peripheral neuropathy.

AIMS: Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Aberrant mitochondrial function causes neurodegeneration under hyperglycemia-induced metabolic stress, which in turn results in DPN progression. m6A and m6A reader (YTHDC2) are closely related to diabetes and diabetes complications, while the role of YTHDC2 in regulating mitochondrial metabolism in DPN needs to be further probed. METHODS: For HG treatment, Schwann cells (RSC96) were subjected to D-glucose for 72 h. db/db mice were used as the diabetic mouse model. Me-RIP assay was performed to evaluate KDM5B m6A level. RNA degradation assay was conducted to examine KDM5B mRNA stability. In addition, OCR and ECAR were examined by XF96 Analyzer. Moreover, the content of ATP and PDH activity in RSC96 cells were detected using kits, and the level of ROS was detected using MitoSOX staining. RIP, RNA pull-down and dual-luciferase reporter gene assays were carried out to verify the binding relationships between YTHDC2, KDM5B and SIRT3. RESULTS: We first observed that KDM5B expression and KDM5B mRNA stabilization were significantly increased in DPN. The m6A reader YTHDC2 was lowly expressed in DPN. Meanwhile, YTHDC2 over expression decreased KDM5B mRNA stability in an m6A-dependent manner. Our results also revealed that YTHDC2 overexpression resulted in reduced ROS level and increased ATP level, PDH activity, OCR and ECAR in HG-treated Schwann cells, while these effects were reversed by KDM5B overexpression. Additionally, SIRT3 served as the target of YTHDC2/KDM5B axis in regulating mitochondrial metabolism in DPN. CONCLUSIONS: Taken together, YTHDC2 promoted SIRT3 expression by reducing the stabilization of KDM5B to improve mitochondrial metabolic reprogramming in DPN.

Subtotal Fenestrating Cholecystectomy: A Safe and Effective Approach to the Difficult Gallbladder.

INTRODUCTION: Subtotal laparoscopic cholecystectomy (SUB) is an alternative to total laparoscopic cholecystectomy (TOT) when the critical view of safety (CVS) cannot be achieved. Little is known about the clinical factors and postoperative outcomes associated with SUB. The objective was to determine predictive factors and outcomes of SUB as compared to TOT. METHODS: Clinical data from patients admitted from our emergency department to the acute care surgery service who underwent SUB or TOT by an acute care surgery surgeon for acute biliary disease (2017-2019) were reviewed. Wilcoxon rank-sum and Fisher's exact tests were used. RESULTS: 355 patients underwent cholecystectomy for acute cholecystitis; 28 were SUB (7.9%). SUB patients were more likely to be older (57 versus 43 y; P = 0.015), male (60.7% versus 39.3%; P < 0.001), have a history of cirrhosis or liver disease (14.3% versus 2.1%; P = 0.007), and have a higher Charlson-Comorbidity Index (1 versus 0, P = 0.041). SUB had greater leukocytosis (14.6 versus 10.9; P < 0.001), higher total bilirubin (0.9 versus 0.6; P = 0.021), and a higher Tokyo grade (2 versus 1; P < 0.001), and had operative findings including gallbladder decompression (82.1% versus 23.2%; P < 0.001) and inability to achieve the CVS (78.6% versus 3.4%; P < 0.001). SUB patients had an increased length of stay (4 versus 2 d; P < 0.001) and more 1-y readmissions. No major vascular injuries occurred in either group with one biliary injury in the TOT group. CONCLUSIONS: SUB patients present with more significant markers of biliary disease and have more complicated intraoperative and postoperative courses. However, the lack of biliary or vascular injuries suggests that SUB may represent a safe alternative when the CVS cannot be achieved.

Lysine demethylase KDM5B down-regulates SIRT3-mediated mitochondrial glucose and lipid metabolism in diabetic neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes mellitus without efficient interventions. Both lysine demethylase 5B (KDM5B) and sirtuin-3 (SIRT3) have been found to regulate islet function and glucose homeostasis. KDM5B was predicted to bind to the SIRT3 promoter by bioinformatics. Here, we investigated whether KDM5B affected DPN development via modulating SIRT3. METHODS: The db/db mice and high glucose-stimulated Schwann cells (RSC96) were used as in vivo and in vitro models of DPN, respectively. Glucose level, glucose and insulin tolerance of mice were measured. Neurological function was evaluated by motor nerve conduction velocity (MNCV), tactile allodynia assay and thermal sensitivity assay. Adenosine triphosphate level, oxygen consumption rate, extracellular acidification rate, ß-oxidation rate, acetyl-CoA level, acetylation levels and activities of long-chain acyl CoA dehydrogenase (LCAD) and pyruvate dehydrogenase (PDH) were detected. Methyl thiazolyl tetrazolium assay was adopted to determine cell viability. Reactive oxygen species (ROS) production was detected by MitoSox staining. Western blotting for measuring target protein levels. Molecular mechanisms were investigated by co-immunoprecipitine (Co-IP), chromatin immunoprecipitation (ChIP) and luciferase reporter assay. RESULTS: KDM5B was up-regulated, while SIRT3 was down-regulated in DPN models. SIRT3 overexpression or AMPK activation ameliorated mitochondrial metabolism dysfunction and ROS overproduction during DPN. KDM5B overexpression triggered mitochondrial metabolism disorder and oxidative stress via directly transcriptional inhibiting SIRT3 expression by demethylating H3K4me3 or indirectly repressing AMPK pathway-regulated SIRT3 expression. CONCLUSION: KDM5B contributes to DPN via regulating SIRT3-mediated mitochondrial glucose and lipid metabolism. KDM5B inhibition may be an effective intervention for DPN.

Review of constructing animal models of depression after myocardial infarction / 中国药理学通报

The incidence of depression after myocardial infarction (DAMI) is high, causing significant harm to the patients' physical and mental health, but the pathogenesis is unknown. Establishing animal models which simulate the pathogenesis of DAMI in humans is an effective way to explore the mechanism of the disease. In this paper, problems existing in the modeling process, such as animal selection, model selection, model preparation and behavioral evaluation, are summarized and considered in order to provide reference for DAMI model research.

Mechanism of stress-induced microglial activation in depression and traditional Chinese medicine regulation / 中国中药杂志

Depression exists with high prevalence and heavy disease burden. Stress events play a key role in the occurrence of depression, but the pathological mechanism has not been fully clarified by reason of the complexity and heterogeneity. In recent years, neuroinflammation as a pathological mechanism of depression has received extensive attention. The activated microglia is regarded as the marker of neuroinflammation, which is an important link of stress-induced depression. Stress might induce microglia activation through pattern recognition receptors(PRR), intestinal flora, hypothalamic-pituitary-adrenal(HPA) axis, and other pathways. Cross-talk between impaired microglia function and neurobiological factors such as inflammatory cytokines, serotonin metabolism, and neuroplasticity may lead to depression. At present, a large number of studies have proved that traditional Chinese medicine(TCM) plays an anti-depressive role by inhibiting microglia activation, which may be potential treatment strategies for depressive disorder. This paper reviewed the research progress of stress-induced microglia activation in depression and summarized the mechanism of TCM against depression with regard to microglia, hoping to provide experimental evidence and consideration for TCM against depression through microglia.

Iris metastasis from clear cell renal cell carcinoma: A case report.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common type of tumor that can metastasize to any organs and sites. However, it is extremely rare for ccRCC to metastasize to the iris. Here, we describe a rare case of iris metastasis from ccRCC with a history of left nephrectomy in 2010. CASE SUMMARY: A 62-year-old male was admitted to the hospital due to blurred vision and red eyes, and a mass was found on the iris in the right eye. B-scan ultrasonography revealed a well-bounded high-density lesion at the corner of the anterior chamber at the 3-4 o'clock position. Phacoemulsification with simultaneous intraocular lens implantation and iridocyclectomy was performed in the right eye. The lesion was confirmed to be metastatic ccRCC by histological and immunohistochemical analyses. The patient was still alive at 9 mo after surgical treatment. Ocular metastasis can be an initial sign with a poor prognosis. Timely detection and treatment may improve survival. Clinicians should pay attention to similar metastatic diseases to prevent misdiagnosis leading to missed treatment opportunities. CONCLUSION: This report of the characteristics and successful management of a rare case of iris metastasis from ccRCC highlights the importance of a comprehensive medical history, histopathology, immunohistochemistry, and clinical manifestation for successful disease diagnosis.