Icariin ameliorates glycolytic dysfunction in Alzheimer's disease models by activating the Wnt/ß-catenin signaling pathway.

It was reported that the Wnt/ß-catenin pathway is involved in the regulation of aerobic glycolysis and that brain glycolytic dysfunction results in the development of Alzheimer's disease (AD). Icariin (ICA), an active component extracted from Epimedii Folium, has been reported to produce neuroprotective effects in multiple models of AD, but its underlying mechanism remains to be fully described. We aimed to investigate the protective effects of ICA on animal and cell models of AD and confirm whether the Wnt/ß-catenin pathway has functions in the neuroprotective function of ICA. The 3 × Tg-AD mice were treated with ICA. HT22 cells, the Aß25-35 peptide and Dickkopf-1 (DKK1) agent (a specific inhibitor of the Wnt/ß-catenin pathway) were used to further explore the underlying mechanism of ICA that produces anti-AD effects. Behavioral examination, western blotting assay, staining analysis, biochemical test, and lactate dehydrogenase (LDH) assays were applied. We first demonstrated that ICA significantly improved cognitive function and autonomous behavior, reduced neuronal damage, and reversed the protein levels and activities of glycolytic key enzymes, and expression of protein molecules of the canonical Wnt signaling pathway, in 3 × Tg-AD mice back to wild-type levels. Next, we further found that ICA increased cell viability and effectively improved the dysfunctional glycolysis in HT22 cells injured by Aß25-35 . However, when canonical Wnt signaling was inhibited by DKK1, the above effects of ICA on glycolysis were abolished. In summary, ICA exerts neuroprotective effects in 3 × Tg-AD animals and AD cellular models by enhancing the function of glycolysis through activation of the Wnt/ß-catenin pathway.

Association between esketamine interventions and postpartum depression and analgesia following cesarean delivery: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare the efficacy and safety of the use of esketamine to reduce the risk for postpartum depression and pain after cesarean delivery. DATA SOURCES: Literature searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wan fang from inception to August 2023. STUDY ELIGIBILITY CRITERIA: The eligibility criteria were all randomized controlled trials of people who underwent a cesarean delivery and who were randomized to receive esketamine interventions irrespective of age or ethnicity. The outcomes that were assessed included the incidence of postpartum depression and the Edinburgh Postnatal Depression Scale score within 7 days and at 28 to 42 days after delivery, the pain score (visual analog scale or numerical rating scale, 0-10), the consumption of opioids, and intraoperative and postoperative adverse events. METHODS: The Cochrane collaboration's tool was used for quality appraisal of the included studies. Statistical analysis of the data was performed using Review Manager 5.3 software, and the results were expressed as mean differences with 95% confidence intervals. Assessments were pooled using a random-effects or fixed-effects model. Study heterogeneity was assessed using the standard I2 statistic. RESULTS: Among the 11 included randomized controlled trials that used the Edinburgh Postnatal Depression Scale for postpartum depression assessment, patients in esketamine group had a lower risk for postpartum depression within a week of surgery (risk ratio, 0.45; 95% confidence interval, 0.33-0.62). Intraoperative use of esketamine maintained a lower Edinburgh Postnatal Depression Scale score after surgery (mean difference, -1.64; 95% confidence interval, -2.14 to -1.14). Esketamine was associated with a beneficial effect in terms of the other outcomes, including a significant decline in pain score within 48 hours (mean difference, -0.71; 95% confidence interval, -0.89 to 0.52). Esketamine increased the risk for adverse neurologic and mental events during surgery without harming health, and there was no significant difference after delivery when compared with the control group. CONCLUSION: Esketamine may reduce the risk for postpartum depression among patients who are undergoing cesarean delivery in the short term. In addition, as an adjunct to reduce analgesia, esketamine also effectively assists in pain management. Because of the lack of more high-quality evidence, we need more compelling evidence to confirm the value of esketamine in improving postpartum recovery.

Predictive value of combination of lung injury prediction score and receptor for advanced glycation end­products for the occurrence of acute respiratory distress syndrome.

The present study evaluated the predictive value of the combination of the lung injury prediction score (LIPS) and receptor for advanced glycation end-products (RAGE) for the occurrence of acute respiratory distress syndrome (ARDS) in critically ill patients with ARDS risk factors. A total of 551 patients with risk factors of ARDS were divided into an ARDS group and a non-ARDS group. LIPS was computed within 6 h of admission into the ICU, and the plasma concentration of RAGE was detected within 24 h of admission. Multivariate analysis was performed to identify independent associations, and the predictive values for ARDS occurrence were assessed with receiver operating characteristic (ROC) curve. Within 7 days after admission into the ICU, ARDS occurred in 176 patients (31.9%). Multivariate analysis demonstrated that LIPS [odds ratio (OR), 1.282; 95% confidence interval (CI), 1.108-1.604], RAGE levels (OR, 2.359; 95% CI, 1.351-4.813) and Acute Physiology and Chronic Health Evaluation II score (OR, 1.167; 95% CI, 1.074-1.485) were independently associated with ARDS occurrence. ROC curves demonstrated that the area under curve (AUC) of LIPS, RAGE levels and their combination was 0.714 [standard error (SE), 0.023; 95% CI, 0.670-0.759], 0.709 (SE, 0.025; 95% CI, 0.660-0.758) and 0.889 (SE, 0.014; 95% CI, 0.861-0.917), respectively. The AUC of LIPS combined with RAGE levels was significantly higher compared with those of LIPS (0.889 vs. 0.714; Z=6.499; P<0.001) and RAGE (0.889 vs. 0.709; Z=6.282; P<0.001) levels alone. In conclusion, both LIPS and RAGE levels were independently associated with ARDS occurrence in critically ill patients with ARDS risk factors, and had medium predictive values for ARDS occurrence. Combination of LIPS with RAGE levels increased the predictive value for ARDS occurrence.

Blood-brain barrier dysfunction mediated by the EZH2-Claudin-5 axis drives stress-induced TNF-α infiltration and depression-like behaviors.

Growing evidence suggests that neurovascular dysfunction characterized by blood-brain barrier (BBB) breakdown underlies the development of psychiatric disorders, such as major depressive disorder (MDD). Tight junction (TJ) proteins are critical modulators of homeostasis and BBB integrity. TJ protein Claudin-5 is the most dominant BBB component and is downregulated in numerous depression models; however, the underlying mechanisms remain elusive. Here, we demonstrate a molecular basis of BBB breakdown that links stress and depression. We implemented an animal model of depression, chronic unpredictable mild stress (CUMS) in male C57BL/6 mice, and showed that hippocampal BBB breakdown was closely associated with stress vulnerability. Concomitantly, we found that dysregulated Cldn5 level coupled with repression of the histone methylation signature at its promoter contributed to stress-induced BBB dysfunction and depression. Moreover, histone methyltransferase enhancer of zeste homolog 2 (EZH2) knockdown improved Cldn5 expression and alleviated depression-like behaviors by suppressing the tri-methylation of lysine 27 on histone 3 (H3K27me3) in chronically stressed mice. Furthermore, the stress-induced excessive transfer of peripheral cytokine tumor necrosis factor-α (TNF-α) into the hippocampus was prevented by Claudin-5 overexpression and EZH2 knockdown. Interestingly, antidepressant treatment could inhibit H3K27me3 deposition at the Cldn5 promoter, reversing the loss of the encoded protein and BBB damage. Considered together, these findings reveal the importance of the hippocampal EZH2-Claudin-5 axis in regulating neurovascular function and MDD development, providing potential therapeutic targets for this psychiatric illness.

Effect of electroacupuncture at "Neiguan" (PC 6) and "Zusanli" (ST 36) on gastrointestinal hormone in the antral tissue of rats with functional dyspepsia. / 电针"å† å ³""足三里"å¯¹åŠŸèƒ½æ€§æ¶ˆåŒ–ä¸è‰¯å¤§é¼ èƒƒçª¦ç»„ç»‡èƒƒè‚ æ¿€ç´ çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD. METHODS: A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats. RESULTS: In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group. CONCLUSIONS: Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.

Suppression of hnRNP A1 binding to HK1 RNA leads to glycolytic dysfunction in Alzheimer's disease models.

Objective: To investigate the mechanism of RNA-binding protein hnRNP A1 in mouse hippocampal neurons (HT22) on glycolysis. Methods: RIP and CLIP-qPCR were performed by HT22 in vitro to observe the mechanism of hnRNP A1 regulating the expression of key proteins in glycolysis. The RNA binding domain of hnRNP A1 protein in HT22 was inhibited by VPC-80051, and the effect of hnRNP A1 on glycolysis of HT22 was observed. Lentivirus overexpression of hnRNP A1 was used to observe the effect of overexpression of hnRNP A1 on glycolysis of Aß25-35-injured HT22. The expression of hnRNP A1 in brain tissues of wild-type mice and triple-transgenic (APP/PS1/Tau) AD mice at different ages was studied by Western blot assay. Results: The results of RIP experiment showed that hnRNP A1 and HK1 mRNA were significantly bound. The results of CLIP-qPCR showed that hnRNP A1 directly bound to the 2605-2821 region of HK1 mRNA. hnRNP A1 inhibitor can down-regulate the expression of HK1 mRNA and HK1 protein in HT22 cells. Overexpression of hnRNP A1 can significantly reduce the toxic effect of Aß25-35 on neurons via the hnRNP A1/HK1/ pyruvate pathway. In addition, inhibition of hnRNP A1 binding to amyloid precursor protein (APP) RNA was found to increase Aß expression, while Aß25-35 also down-regulated hnRNP A1 expression by enhancing phosphorylation of p38 MAPK in HT22. They interact to form bidirectional regulation, further down-regulating the expression of hnRNP A1, and ultimately aggravating glycolytic dysfunction. Protein immunoblotting showed that hnRNP A1 decreased with age in mouse brain tissue, and the decrease was greater in AD mice, suggesting that the decrease of hnRNP A1 may be a predisposed factor in the pathogenesis of AD.

The safety and efficacy of remimazolam tosylate combined with propofol in upper gastrointestinal endoscopy: A multicenter, randomized clinical trial.

INTRODUCTION: Hypotension is the most common adverse event under propofol-mediated sedation and is possible to cause varying degrees of damage to patients. Whereas remimazolam has a poorer sedative effect than propofol. AIM: The aim of this study was to explore the advantages of the combination of remimazolam tosylate and propofol. METHODS: 304 patients were divided into the remimazolam tosylate group (RT group), the propofol group (P group), and the remimazolam tosylate plus propofol group(R+T group). The primary outcome was the incidence of hypotension. Secondary outcomes included the results of sedation and recovery. The safety results mainly include the incidence of Hypotension, adverse respiratory events, postoperative nausea and vomiting, hiccup, cough, body movement and bradycardia. RESULTS: The incidence of hypotension was 56.7% in the P group, 12.6% in the RT group, and 31.3% in the R+P group, three groups of pairwise comparisons showed statistical differences, with P< 0.001. The incidence of body movement was significantly higher in the RT group (26.1%) than in the P group (10.3%) and the R+P group (12.5%), P = 0.004. The endoscopist satisfaction was higher in the P (3.87±0.44) and R+P (3.95±0.22)groups than in the RT(3.53±0.84) group. The incidence of adverse events, in descending order, was P group, RT group, and R+P group (93.8%vs.61.3%vs.42.7%). CONCLUSION: Co-administration had fewer adverse events than propofol monotherapy, also had a better sedative effect and higher endoscopist satisfaction than remimazolam monotherapy. TRIAL REGISTRATION: Clinical trial registration number: NCT05429086.

[An anti-scald device for warm needling].

Warm needling, i.e. acupuncture with the needle warmed by burning moxa stick or cone, is frequently employed in the treatment of cold and dampness type disorders. During treatment, accidental skin scald may occur if the burning moxa drops on the skin due to slight changes in patient's body position. Thus, we designed and developed an anti-scald device for warm needling which is suitable for any part of the body. This device is made up of two parts, a stainless steel-grid moxa cartridge (including half cylinder, hinge shaft, lug, limit bar, clamping arm, connecting arm, torsion spring, heat insulation pad, through holes) and a clamp holder which is in an integrated structure. The grid moxa cartridge can be used to wrap the burning mugwort cone in all directions to prevent the ignited moxa-cone from falling and skin scalding, and effectively collect the burned moxa ash. At the same time, the clamp holder can be used to help fix the moxa-cone to increase the stability of warm needling operation. The device is convenient to operate and novel in design, can effectively reduce the occurrence of scald accidents in clinical treatment, save time and manpower, and has both economic and ecological benefits, being helpful to the promotion and use of warm needling.

Correction: Clinical correlation between serum cytokines and the susceptibility to Polygonum multiflorum-induced liver injury and an experimental study.

Correction for 'Clinical correlation between serum cytokines and the susceptibility to Polygonum multiflorum-induced liver injury and an experimental study' by Le Zhang et al., Food Funct., 2022, 13, 825-833, https://doi.org/10.1039/D1FO03489H.

A case report of ciprofol overdose during anesthesia/analgesia and literature review: clinical presentation, blood pressure, and management.

Ciprofol is a novel intravenous anesthetic agent and a highly selective gamma-aminobutyric acid-A receptor agonist, similar to propofol. This is the first report about ciprofol overdose occurring during the maintenance phase of anesthesia for a surgical intervention. The accidental administration of an excessive ciprofol dose to a 37-year-old woman admitted to our hospital for laparoscopic myomectomy occurred during the first 3 minutes of maintenance anesthesia, in which the administered dose was 3.67 mg/kg instead of 0.06 mg/kg. The patient's bispectral index (BIS) decreased to 0 after 6 minutes and returned to 26 after 23 minutes, after which the surgery was restarted and successfully completed with the planned ciprofol maintenance anesthesia dose. During the 23 minutes after ciprofol overdose, the patient's vital signs were stable with the lowest mean arterial pressure being 69.3 mmHg. The patient regained consciousness quickly and recovered well after myomectomy. The patient's BIS decreased progressively, whereas her blood pressure, heart rate, and oxygen saturation did not change significantly. In the present case of ciprofol overdose, the observed stable blood pressure protected against organ injury during laparoscopic myomectomy.

New insights into the pathogenesis of Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is characterized by defects of multiple tissue-specific lysosome-related organelles (LROs), typically manifesting with oculocutaneous albinism or ocular albinism, bleeding tendency, and in some cases with pulmonary fibrosis, inflammatory bowel disease or immunodeficiency, neuropsychological disorders. Eleven HPS subtypes in humans and at least 15 subtypes in mice have been molecularly identified. Current understanding of the underlying mechanisms of HPS is focusing on the defective biogenesis of LROs. Compelling evidences have shown that HPS protein-associated complexes (HPACs) function in cargo transport, cargo recycling, and cargo removal to maintain LRO homeostasis. Further investigation on the molecular and cellular mechanism of LRO biogenesis and secretion will be helpful for better understanding of its pathogenesis and for the precise intervention of HPS.

Clinical correlation between serum cytokines and the susceptibility to Polygonum multiflorum-induced liver injury and an experimental study.

Polygonum multiflorum (PM), a popular functional food, and a herbal and dietary supplement, is widely used as a tonic in China and East Asia. In recent years, it has attracted great concern for its ability to cause idiosyncratic drug-induced liver injury (IDILI). However, identifying individuals susceptible to IDILI remains challenging. This is a prospective study. For 6 patients whose serum alanine aminotransferase (ALT) levels after consuming PM were abnormally elevated (susceptible group), 15 patients with normal levels of liver injury markers were matched (tolerant group) based on similar baseline characteristics. ProcartaPlex immunoassays were adopted to quantitatively detect 33 serum cytokines in the two groups of patients before consuming PM, to characterize the cytokine profile and screen differential cytokines. Subsequently, the susceptibility of a potential biomarker to regulate PM-induced liver injury was validated in animal models. There were significant differences in the cytokine profiles between the susceptible and tolerant groups, wherein the susceptible patients showed immune perturbation characterized by high expression of multiple inflammatory cytokines, especially the proinflammatory cytokine TNF-α (P = 0.006). Among them, the cytokine TNF-α had the strongest correlation with ALT, where the correlation coefficient was greater than 0.6, and the area under the receiver operating characteristic curve was more than 0.8. Animal experiments revealed that both PM water extract and its susceptibility component of liver injury, cis-stilbene glucoside, could cause liver injury in the mice pre-stimulated using TNF-α. Conversely, administration of the same dose of drugs on control mice did not show any hepatotoxicity. In conclusion, immune perturbation mainly mediated by TNF-α may regulate the susceptibility to PM-induced liver injury. This provides a new perspective for the study of susceptibility to IDILI.

Inhibition of DNA methylation de-represses peroxisome proliferator-activated receptor-γ and attenuates pulmonary fibrosis.

BACKGROUND AND PURPOSE: Development of pulmonary fibrosis is associated with altered DNA methylation modifications of fibrogenic gene expression. However, their causal relationships and the underlying mechanisms remain unclear. This study investigates the critical role of DNA methylation aberration-associated suppression of peroxisome proliferator-activated receptor-γ (PPARγ) in pulmonary fibrosis. EXPERIMENTAL APPROACH: Expression of PPARγ and bioactive DNA methyltransferases (DNMTs) and PPARγ promoter methylation status were examined in fibrotic lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin (Blm)-treated mice. DNA demethylating agent 5-aza-2'-deoxycytidine (5aza) and glycyrrhizic acid (GA) derived from medicinal plant were assessed for their PPARγ de-repression and anti-pulmonary fibrosis activities. PPARγ knockout mice were created to determine the critical role of PPARγ in this protection. KEY RESULTS: Lung PPARγ expression was markedly suppressed in IPF patients and Blm mice, accompanied by increased DNMT 1/DNMT3a and PPARγ promoter hypermethylation. Administration of 5-aza and GA similarly demethylated PPARγ promoter, restored PPARγ loss and alleviated fibrotic lung pathologies, including structural alterations and adverse expression of fibrotic mediators and inflammatory cytokines. In cultured lung fibroblasts and alveolar epithelial cells, GA alleviated PPARγ-mediated suppression of fibrosis in a gain of DNMT-sensitive manner, and in PPARγ knockout mice, the anti-fibrotic effects of 5aza and GA were significantly reduced, suggesting that PPARγ is a critical mediator of epigenetic pulmonary fibrogenesis. CONCLUSION AND IMPLICATIONS: Aberrant DNMT1/3a elevations and the resultant PPARγ suppression contribute significantly to the development of pulmonary fibrosis, and strategies targeting DNMT/PPARγ axis with synthetic or natural compounds might benefit patients with pulmonary fibrotic disorders.

Inhibition of DNA methyltransferase aberrations reinstates antioxidant aging suppressors and ameliorates renal aging.

DNA methylation alterations play mechanistic roles in aging; however, the epigenetic regulators/mediators causally involved in renal aging remain elusive. Here, we report that natural and D-galactose (D-gal)-induced aging kidneys display marked suppression of antiaging factor NRF2 (nuclear factor erythroid-derived 2-like 2) and KLOTHO, accompanied by upregulations of DNA methyltransferase (DNMT) 1/3a/3b and NRF2/KLOTHO gene promoter hypermethylations. Administration of a DNMT inhibitor SGI-1072 effectively hypomethylated the promoters, derepressed NRF2/KLOTHO, and mitigated the structural and functional alterations of renal aging in D-gal mice. Moreover, oleuropein (OLP), an olive-derived polyphenol, also displayed similar epigenetic modulation and antiaging effects. OLP inhibited the epigenetic NRF2/KLOTHO suppressions in a gain of DNMT-sensitive manner in cultured renal cells, demonstrating a strong DNA-demethylating capacity. In NRF2 knockout and KLOTHO knockdown D-gal mice, OLP exhibited reduced antiaging effects with KLOTHO displaying a prominent gene effect and effect size; consistently in KLOTHO knockdown mice, the antiaging effects of SGI-1027 were largely abrogated. Therefore, the KLOTHO recovery is critical for the antiaging effects of DNA demethylation. Collectively, our data indicate that aberrant DNMT1/3a/3b elevations and the resultant suppression of antiaging factors contribute significantly to epigenetic renal aging, which might be targeted for epigenetic intervention by synthetic or natural DNA-demethylating agents.

Fungi-Bacteria Associations in Wilt Diseased Rhizosphere and Endosphere by Interdomain Ecological Network Analysis.

In the plant rhizosphere and endosphere, some fungal and bacterial species regularly co-exist, however, our knowledge about their co-existence patterns is quite limited, especially during invasion by bacterial wilt pathogens. In this study, the fungal communities from soil to endophytic compartments were surveyed during an outbreak of tobacco wilt disease caused by Ralstonia solanacearum. It was found that the stem endophytic fungal community was significantly altered by pathogen invasion in terms of community diversity, structure, and composition. The associations among fungal species in the rhizosphere and endosphere infected by R. solanacearum showed more complex network structures than those of healthy plants. By integrating the bacterial dataset, associations between fungi and bacteria were inferred by Inter-Domain Ecological Network (IDEN) approach. It also revealed that infected samples, including both the rhizosphere and endosphere, had more complex interdomain networks than the corresponding healthy samples. Additionally, the bacterial wilt pathogenic Ralstonia members were identified as the keystone genus within the IDENs of both root and stem endophytic compartments. Ralstonia members was negatively correlated with the fungal genera Phoma, Gibberella, and Alternaria in infected roots, as well as Phoma, Gibberella, and Diaporthe in infected stems. This suggested that those endophytic fungi may play an important role in resisting the invasion of R. solanacearum.

Budd-Chiari syndrome associated with liver cirrhosis: A case report.

BACKGROUND: Budd-Chiari syndrome (BCS) is a rare heterogeneous liver disease characterized by obstruction of the hepatic venous outflow tract. The incidence of BCS is so low that it is difficult to detect in general practice and difficult to include within the scope of routine diagnosis. The clinical manifestations of BCS are not specific; hence, BCS tends to be misdiagnosed. CASE SUMMARY: We report the case of a 33-year-old Chinese woman who presented with progressive distension in the upper abdomen. She was initially misdiagnosed with liver cirrhosis (LC) due to abnormalities on an upper abdominal computed tomography scan. Although she was taking standard anti-cirrhosis therapy, her symptoms did not improve. Magnetic resonance imaging showed caudate lobe hypertrophy; and dilated lumbar and hemiazygos veins. Venography revealed membranous obstruction of the inferior vena cava owing to congenital vascular malformation. A definitive diagnosis of BCS was made. Balloon angioplasty was performed to recanalize the obstructed inferior vena cava and the patient's symptoms were completely resolved. CONCLUSION: BCS lacks specific clinical features and can eventually lead to LC. Clinicians and radiologists must carefully differentiate BCS from LC. Correct diagnosis and timely treatment are vital to the patient's health.

Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans.

BACKGROUND: Drug-induced liver injury is a common adverse effect in clinical practice, with severe cases resulting in liver failure and even death. Identification and prediction of individuals susceptible to idiosyncratic DILI continues to remain a challenge. METHODS: In this study, we report that cytokines in human serum can be used to identify and predict individuals susceptible to Polygonum multiflorum-induced DILI (PM-DILI) in retrospective and prospective cohort studies. FINDINGS: In the retrospective pilot study, we compared serum cytokine expression profiles of the PM-DILI group (n=10) and the PM-Tolerant group (n=12) and found 10 cytokines with significant differences. In the replication cohort study, differences in the 10 cytokines between PM-DILI (n =11) and PM-Tolerant (n=13) groups were verified. Among them, 6 cytokines showed no significant differences at two time points, including liver injury and recovery stage of PM-DILI, suggesting that these 6 cytokines have no correlation with PM-DILI, however, they may be related to susceptibility. Furthermore, all the retrospective cohorts were combined, and a PM-DILI susceptibility prediction model was built by screening the 6 cytokines. The combination of (TNF-α and CCL-2) or VEGF showed the highest sensitivity and specificity. Finally, the efficacy of the above 3 cytokine combination models in predicting PM-DILI-susceptible individuals was verified before PM exposure in another independent prospective cohort (n=24), with sensitivity and specificity of 66.7% and 83.3%, respectively. CONCLUSION: This proof-of-concept study demonstrates that the serum cytokine combination reflecting dysimmunity could be used as a new method to predict PM-DILI, thus providing a new perspective for improving the clinical management of IDILI.

Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis.

Osteoporosis (OP) is a common skeletal disease involving low bone mineral density (BMD) that often leads to fragility fracture, and its development is affected by multiple cellular pathologies and associated with marked epigenetic alterations of osteogenic genes. Proper physical exercise is beneficial for bone health and OP and reportedly possesses epigenetic modulating capacities; however, whether the protective effects of exercise on OP involve epigenetic mechanisms is unclear. Here, we report that epigenetic derepression of nuclear factor erythroid derived 2-related factor-2 (Nrf2), a master regulator of oxidative stress critically involved in the pathogenesis of OP, mediates the significant osteoprotective effects of running exercise (RE) in a mouse model of OP induced by ovariectomy. We showed that Nrf2 gene knockout (Nfe2l2-/-) ovariectomized mice displayed a worse BMD reduction than the controls, identifying Nrf2 as a critical antiosteoporotic factor. Further, femoral Nrf2 was markedly repressed with concomitant DNA methyltransferase (Dnmt) 1/Dnmt3a/Dnmt3b elevations and Nrf2 promoter hypermethylation in both patients with OP and ovariectomized mice. However, daily 1-h treadmill RE significantly corrected epigenetic alterations, recovered Nrf2 loss and improved the femur bone mass and trabecular microstructure. Consistently, RE also normalized the adverse expression of major osteogenic factors, including osteoblast/osteoclast markers, Nrf2 downstream antioxidant enzymes and proinflammatory cytokines. More importantly, the RE-conferred osteoprotective effects observed in the wild-type control mice were largely abolished in the Nfe2l2-/- mice. Thus, Nrf2 repression due to aberrant Dnmt elevation and subsequent Nrf2 promoter hypermethylation is likely an important epigenetic feature of the pathogenesis of OP, and Nrf2 derepression is essential for the antiosteoporotic effects of RE.

Montmorillonite-supported nanoscale zero-valent iron for thiamethoxam removal: response surface optimization and degradation pathway.

As a highly efficient insecticide, thiamethoxam was widely used in the world. However, it was bioaccumulative and toxic to aquatic organisms that must be removed from water. In this work, nanoscale zero-valent iron particles loaded on montmorillonite (nZVI/Mt) were successfully synthesized for effective removal of thiamethoxam. The properties of nZVI/Mt for the removal of thiamethoxam were investigated, and the reaction conditions were optimized through response surface methodology. Furthermore, the degradation products were analyzed by liquid chromatography-mass spectrometry (LC/MS). The results demonstrated that the reaction activity of nZVI was enhanced because the agglomeration and oxidation of nZVI particles were effectively inhibited by using montmorillonite as a support. The significance of the effects of each factor on the removal of thiamethoxam was determined to be in the order of pH Ëƒ temperature Ëƒ reaction time Ëƒ nZVI/Mt dosage. The optimal conditions were as follows: a dosage of nZVI/Mt of 2 g/L, a reaction time of 2 h, a reaction temperature of 35 °C, and a solution pH of 3. The removal efficiency of thiamethoxam (C0 = 20 mg/L) was observed to be as high as 94.29% under the optimal conditions, which was close to the value of 94.47% that was predicted using the mathematical model, indicating that the model could accurately predict the removal efficiency of thiamethoxam. The degradation mechanism involved the -NO2 group on the thiamethoxam molecule was reduced and eliminated by nZVI/Mt.