The effect of the enhanced recovery after surgery protocol and the reduced use of opioids on postoperative outcomes in elderly patients with colorectal cancer.

OBJECTIVE: The study aimed to assess the impact of the enhanced recovery after surgery (ERAS) pathways and the reduced use of opioids on postoperative outcomes in elderly colorectal cancer (CRC) patients who underwent laparoscopic surgery under general anesthesia (GA). PATIENTS AND METHODS: Clinical data from 99 elderly patients who underwent laparoscopic CRC surgery in the First Affiliated Hospital of Hebei North University from April 2021 to April 2023 were retrospectively analyzed and grouped based on the method of pain control measures received. Of 99 patients, 51 received conventional doses of opioid drugs (conventional group), and 48 patients were treated with reduced doses of opioids based on the principles of ERAS (low-dose group). Perioperative characteristics, postoperative pain level, cognitive function, serum biochemical index levels, and adverse reactions were compared between the two groups. RESULTS: The first exhaust time, defecation time, and bedtime activity time of the low-dose group were compared to the conventional group (p<0.05). On the first day after the surgery, the mini-mental state examination (MMSE) score of the low-dose group was higher than the conventional group (p<0.05). After the surgery, the levels of serum brain-derived neurotrophic factor (BDNF) decreased in both groups, while the levels of neuron-specific enolase (NSE) and 5-hydroxytryptamine (5-HT) increased. However, compared to the conventional group, the low-dose group had higher levels of BDNF and lower levels of NSE and 5-HT (p<0.05). The incidence of adverse reactions in the low-dose group was lower than that in the conventional group (p<0.05). CONCLUSIONS: ERAS protocol and the reduced use of opioid drugs in CRC patients who underwent surgery under GA is associated with an analgesic effect that is comparable to that of conventional opioid use. Reduced dosage of opioid drugs lessened cognitive impairment and lowered the incidence of adverse reactions in surgical patients with CRC.

LncDBH-AS1 knockdown enhances proliferation of non-small cell lung cancer cells by activating the Wnt signaling pathway via the miR-155/AXIN1 axis.

OBJECTIVE: Dys-regulated long noncoding RNAs (lncRNAs) are involved in the cell growth of several malignancies and their aggressive phenotypes. LncRNA DBH-AS1 plays an important role in the advancement of various malignant tumors, but its contribution to non-small cell lung cancer (NSCLC) is still unexplored. This study intends to elucidate the role of the regulatory network of lncRNA DBH-AS1 in NSCLC progression. PATIENTS AND METHODS: The LncDBH-AS1 expression in 32 paired NSCLC patients' tissue samples and NSCLC cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The role of LncDBH-AS1 in NSCLC was investigated through cell counting kit-8 (CCK-8) assay and colony formation assay in vitro. Besides, the interaction between LncDBH-AS1 and miR-155 was also analyzed. RESULTS: The DBH-AS1 expression was significantly down-regulated in NSCLC cell lines and tissue samples. Decreased DBH-AS1 levels promoted the in vitro proliferation of the NSCLC cells. The mechanism was that DBH-AS1 regulated AXIN1 expression by sponging miR-155 in NSCLC cell lines. Importantly, LncDBH-AS1 might inhibit WNT/ß-CATENIN activation in NSCLC cells. CONCLUSIONS: The progression of NSCLC is facilitated by DBH-AS1 via miR-155 interaction and up-regulation of AXIN1 expression.

Role of Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in cardioprotection of exercise preconditioning.

OBJECTIVE: To investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the cardioprotective mechanisms of exercise preconditioning (EP). MATERIALS AND METHODS: Eighty male Sprague-Dawley (SD) rats were randomized into the Group control, Group EE, Group EP+EE, Group EP+EE+AG, and Group EE+AG. By using 3 days of intermittent treadmill exercise, this study established the EP animal model. Rats were subjected to run to exhaustion on the treadmill at 30 m/min with 0% grade as an exhaustive exercise (EE) protocol. The myocardial injury induced by exhaustive exercise was produced 24 h after EP. JAK2 inhibitor (AG490, 3 mg/kg) was injected before EP. Serum cardiac troponin I (cTnI) levels and hematoxylin basic fuchsine picric acid (HBFP) staining were used to observe the degree of myocardial ischemia. TUNEL, Bcl2, and cleaved caspase-3 levels were used to evaluate the change of myocardial apoptosis. Moreover, the phosphorylations of JAK2 and STAT3 were analyzed as possible mechanisms that might explain the EP-induced cardioprotection. RESULTS: EP significantly attenuated the exhaustive exercise-induced myocardial ischemia injury, associated with lower serum cTnI levels, decreased myocardial infarct area, reduced myocardial apoptosis, increased Bcl2 level, decreased cleaved caspase-3 level, and the increased phosphorylations of JAK2 and STAT3. Treatment with AG490 abolished the cardioprotective effects and the enhanced phosphorylations of JAK2 and STAT3 induced by EP. CONCLUSIONS: EP plays its cardioprotective role via activating the JAK2/STAT3 signaling pathway, reducing the apoptosis of myocardial cells and alleviating myocardial ischemia injury.

Does body mass index truly affect mortality and cardiovascular outcomes in patients after coronary revascularization with percutaneous coronary intervention or coronary artery bypass graft? A systematic review and network meta-analysis.

BACKGROUND: Obesity, a comorbid medical condition, is usually observed in patients with established coronary artery disease. Paradoxically, patients with a higher body mass index (BMI) usually have better clinical outcomes after coronary revascularization. METHODS: We searched five online databases through December 2017. We identified studies reporting the rate of all-cause mortality or cardiovascular-related outcomes among patients after coronary revascularization with percutaneous coronary intervention or coronary artery bypass graft based on various BMI categories. Network meta-analysis was performed using Bayesian methods. RESULTS: Sixty-five records involving 865,774 participants were included in our study. A U-shaped association was observed across BMI categories for all-cause mortality. Using normal weight as the reference, all-cause mortality was increased for (relative risk [RR]: 2.4; 95% credibility interval [CrI]: 2.1-2.7) patients with underweight, whereas it was lowered in patients with overweight, obese, and severely obese. This association remained significant in many subgroups. We also observed that the risk of major adverse cardiovascular events (MACE) was lowest among patients with overweight. Furthermore, patients with underweight were associated with greater risks of myocardial infarction (RR: 1.9; 95% CrI: 1.4-2.5), cardiovascular-related mortality (RR: 2.8; 95% CrI: 1.6-4.7), stroke (RR: 2.0; 95% CrI: 1.3-3.3) and heart failure (RR: 1.7; 95% CrI: 1.1-2.7) compared with normal weight patients; no significant association was observed among individuals with higher BMI. CONCLUSIONS: The 'obesity paradox' does exist in patients after coronary revascularization, especially for patients with post-percutaneous coronary intervention. All-cause mortality in patients with high BMI is significantly lower compared with patients with normal weight. Furthermore, patients with underweight experience higher rates of cardiovascular outcomes compared with patients with normal weight.

Oridonin Induces Apoptosis in Human Nasopharyngeal Carcinoma Cells Involving ROS Generation.

Oridonin, an ent-kaurene diterpenoid isolated from the traditional Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide array of cancer cells. However, its effect on human nasopharyngeal carcinoma (NPC) cells has not been well investigated. The present study aimed to explore the anti-tumour effect of oridonin in NPC cells and its underlying mechanisms. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and expression of apoptosis-related proteins were analysed by flow cytometry with propidium iodide staining, JC-1 staining, DCFH-DA staining, and Western blot analysis, respectively. The results showed that oridonin concentration-dependently inhibited the cell viability, decreased the colony formation, and enhanced the apoptotic rate in NPC cells. Further, oridonin-induced apoptosis was mediated by the mitochondrial pathway in NPC cells, which was confirmed by the loss of MMP, downregulation of anti-apoptotic Bcl-2 family protein Mcl-1 and Bcl-2, upregulation of pro-apoptotic Bcl-2 family member Bax, and activation of caspase-3 and PARP. Notably, the augmented ROS generation played an essential role in oridonin-induced apoptosis in NPC cells, as the apoptosis-inducing effect was attenuated by ROS scavenger N-acetyl-L-cysteine. These results indicate that oridonin triggers apoptosis through the ROSmediated mitochondrial pathway in NPC cells. This study supports oridonin to be an interesting candidate drug for the treatment of human NPC.

Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo.

Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer.

Pathway analysis of differentially expressed genes in human esophageal squamous cell carcinoma.

OBJECTIVE: Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common human cancers with a particularly high incidence in certain regions of China. Differentially expressed genes (DEG) between the esophageal squamous carcinoma tissues and matched normal esophageal mucosal epithelial tissues can be detected by employing the gene microarray technology. This can aid the analysis of the underlying disease mechanism and can help to identify potentially critical genes as well as related molecular signalling pathways. MATERIALS AND METHODS: The potentially critical genes and related signal pathways are examined by bioinformatics analysis including Gene Ontology (GO) analysis, pathway analysis and signal transduction networks. Here, we performed microarray analysis with 8 pairs of ESCC and normal esophageal mucosal epithelial tissues. RESULTS: Compared to the control group, 347 and 203 genes were found to be up-regulated and down-regulated in the experimental group, respectively. Based on pathway analysis, 52 and 51 signal transduction pathways were involved in the up-regulated and the down-regulated genes, respectively. SLC27A6, RAB11A, ABCA8, JAM2, HNMT, GSTM1, and CDKN3, which play critical roles in regulating the expression of ESCC, were identified among the key genes involved in the signal transduction networks. CONCLUSIONS: Investigation of the mechanism underlying ESCC can provide a direction for the clinical prevention and treatment of ESCC.

Neither insufficiency nor overexpression of sac1 affects the accumulation of Aß42 in Drosophila expressing Ab42.

OBJECTIVE: We investigated the effects of genetic down- and up-regulation of sac1 expression on Aß42 accumulation and the associated neural deficits in flies with direct expression of arctic mutant Aß42 (Aßarc) in the neurons of GF pathway. MATERIALS AND METHODS: We genetically down-regulated and up-regulated the level of sac1, encoding a major phosphoinositide phosphatases in a disease model, in which arctic mutant Aß42 is directly expressed in the neurons of a neural pathway of adult fruit flies. RESULTS: We conducted a time-course analysis of Aß42 level in the model and found an age-dependent elevation of Aß42 accumulation, closely correlated to the age-dependent decline of climbing ability in the model flies. Neither sac1 insufficiency nor sac1 over-expression significantly changed the three phenotypes. CONCLUSIONS: We found that the alterations of sac1 expression did not change Aß42 accumulation and neural deficits in the model.

Impact of metabolic syndrome on myocardial injury and clinical outcome after percutaneous coronary intervention.

AIMS: This study tested the associations between metabolic syndrome, postprocedural myocardial injury, and clinical outcome after percutaneous coronary intervention. PATIENTS AND METHODS: We evaluated 204 patients who fulfilled the study criteria and were scheduled for elective percutaneous coronary intervention. The patients were divided into a metabolic syndrome group and a control group according to the definition of metabolic syndrome. Creatine kinase-MB and troponin I levels were measured at baseline, at 8 h, and 24 h after the procedure, while clinical outcomes were followed up for 1 year. RESULTS: The incidence of postprocedural myocardial injury was significantly higher in the metabolic syndrome group than in the control group as indicated by either blood creatine kinase-MB elevation (32.9 % vs. 17.2 %, p = 0.010) or troponin I elevation (34.2 % vs. 17.2 %, p = 0.006). Postprocedural peak values of creatine kinase-MB (5.724 ± 7.678 ng/ml vs. 3.097 ± 5.317 ng/ml, p < 0.001) and troponin I (0.066 ± 0.093 ng/ml vs. 0.038 ± 0.079 ng/ml, p < 0.001) were also significantly higher in the metabolic syndrome group than in the control group. On multiple regression analysis, metabolic syndrome was independently associated with troponin I elevation (odds ratio 2.24, 95 % confidence interval, CI, 1.04-4.80, p = 0.039). During the 1-year follow-up, cardiac events occurred in 28.9 % of patients with metabolic syndrome and 17.9 % of controls, and there was a trend toward increased adverse outcomes in the metabolic syndrome group (hazard ratio 1.67, 95 % CI 0.93-3.00, p = 0.071, log rank test). CONCLUSION: The results of this study demonstrate that metabolic syndrome is associated with postprocedural myocardial injury and with increased cardiac events.

A double-blind comparative study of Chinese herbal medicine Jinlianqingre Effervescent Tablets in combination with conventional therapy for the treatment of uncomplicated hand, foot, and mouth disease.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.

Predictive value of penile dynamic colour duplex Doppler ultrasound parameters in patients with posttraumatic urethral stricture.

This study evaluated dynamic colour duplex Doppler ultrasound (D-CDDU) for the assessment of erectile function in patients with post-traumatic urethral stricture. In total, 44 patients with urethral stricture secondary to trauma were recruited between January 2009 and June 2010. Peak systolic velocity of the cavernosal artery was measured before and after intracavernosal injection (ICI) of 20 mg papaverine and 1 mg phentolamine. Cavernosal artery end-diastolic velocity and resistance index (RI) were evaluated after ICI. Patients with RI ≥ 0.8 had significantly shorter strictures than those with RI < 0.8 after ICI only in cases of posterior urethral stricture. Patients with RI ≥ 0.8 were significantly younger than those with RI < 0.8. Urethral stricture length was negatively correlated with RI (r = -0.375). Cavernosal artery RI after ICI is a reliable predictor of erectile function in patients with urethral stricture, especially posterior stricture. The patient's age should be considered when using this parameter.

zVAD-induced necroptosis in L929 cells depends on autocrine production of TNFα mediated by the PKC-MAPKs-AP-1 pathway.

It is intriguing that some pan-caspase inhibitors such as zVAD-fmk (zVAD) are capable of inducing necrotic cell death in a selected group of cells. As earlier reports from our laboratory have ruled out the original notion that zVAD-induced necrosis in mouse fibrosarcoma L929 cells was autophagic cell death, the main objective of this study was thus to determine the underlying mechanism of this form of cell death. In this study, we provided clear evidence that zVAD-induced necroptosis in L929 cells and such cell death is dependent on autocrine production of tumor necrosis factor-α (TNFα) at the transcriptional level. More importantly, we identified that activating protein-1 (AP-1), but not nuclear factor κ-B, is the transcription factor controlling zVAD-induced TNFα transcription. Moreover, zVAD is able to activate AP-1 through activation of two upstream mitogen-activated kinases (MAPKs), c-Jun N-terminal kinase and extracellular signal-regulated kinase. Finally, we found that protein kinase C is the important upstream signaling molecule in mediating zVAD-induced activation of MAPKs and AP-1, and subsequent autocrine production of TNFα and cell death. Data from this study reveal the molecular mechanisms underlying zVAD-induced necroptosis, an important form of programmed necrotic cell death with increasing understanding of its biological significance in health and diseases.

Development of a new model of transvenous thrombosis in the pig superior sagittal sinus using thrombin injection and balloon occlusion.

PURPOSE: To establish an experimental model of superior sagittal sinus (SSS) thrombosis using a transvenous route, and thrombin and balloon occlusion, in pigs. METHODS: The SSS was catheterized transvenously in six pigs. Thrombin was injected into the pigs' SSS to induce thrombosis. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) confirmed successful SSS thrombosis. MRI and MRV were also used to observe the evolution of thrombus and accompanying brain parenchymal changes before thrombus induction postoperatively on Days 1, 3, and 7. The pigs were sacrificed for histological examination at the follow-up. RESULTS: SSS thrombosis was successfully achieved in all six pigs. On Day 1 postoperatively, MRV confirmed SSS thrombosis and MRI revealed brain edema in each animal. On Day 3, venous infarction was noted in two cases, one of which appeared to be hemorrhagic. On Day 7, MRV showed partial recanalization of the SSS in one pig. Brain edema was significantly relieved in four cases while, in two other cases, the extent of venous infarction was reduced. Histological examination confirmed SSS thrombosis in all animals, with recanalization in only one case. In two of the animals, bilateral parasagittal infarction was seen, including one with petechial hemorrhage. In the other four animals, bilateral parasagittal edema was observed. CONCLUSION: The development of an experimental model of SSS via the transvenous route is feasible in pigs using thrombin and balloon occlusion. This model closely resembles SSS thrombosis in humans, and can be applied in the clinical study of this phenomenon as well as in clinical therapeutic applications.

Maxillary sinus floor elevation using a tissue-engineered bone complex with beta-TCP and BMP-2 gene-modified bMSCs in rabbits.

OBJECTIVES: To study the effects of maxillary sinus floor elevation by a tissue-engineered bone complex with beta tricalcium phosphate (beta-TCP) and bone morphogenetic protein-2 (BMP-2) gene-modified bone marrow stromal cells (bMSCs) in rabbits. MATERIAL AND METHODS: bMSCs derived from New Zealand rabbit bone marrow were cultured and transduced with the adenovirus with BMP-2 (AdBMP-2), adenovirus with enhanced green fluorescent protein gene (AdEGFP) in vitro. Gene transfer efficiency was detected by EGFP expression. These gene-modified autologous bMSCs were then combined with a beta-TCP granule scaffold at a concentration of 2 x 10(7) cells/ml and used to elevate the maxillary sinus floor in rabbits. Twenty rabbits were randomly allocated into groups and sacrificed at weeks 2 and 8. For each time point, 20 maxillary sinus floor elevation surgeries were made bilaterally in 10 rabbits for the following groups (n=5 per group): group A (beta-TCP alone), group B (untransduced bMSCs/beta-TCP), group C (AdEGFP-bMSCs/beta-TCP), and group D (AdBMP-2-bMSCs/beta-TCP). All samples were evaluated by histology and histomorphometric analysis. The fate of implanted bMSCs was traced initially by a confocol fluorescent microscope in the AdEGFP group. RESULTS: Gene transfer efficiency reached up to 60-80% with 50 PFU/cell transduction as demonstrated by fluorescent microscopic analysis in the AdEGFP group. The augmented maxillary sinus height was maintained for the four groups till 8 weeks post-surgery, while new bone area increased over the time. At week 2, bone areas in groups B-D were significantly larger than those in group A, while at week 8, in group D, the BMP-2 gene-enhanced tissue-engineered bone had the largest bone area among the groups (P<0.05, ANOVA). In that group, a mature bone structure was detected in the center of the elevated space. Under a confocal microscope, green fluorescence in newly formed bone was observed for the EGFP group, which suggested that those implanted bMSCs might have contributed to the new bone formation. CONCLUSION: bMSCs modified with the AdBMP-2 gene can promote new bone formation and maturation in the rabbit maxillary sinus. BMP-2 regional gene therapy and a tissue engineering technique could be effectively used in maxillary sinus elevation and bone regeneration.

Hyperbaric oxygen preconditioning reduces ischemia-reperfusion injury by inhibition of apoptosis via mitochondrial pathway in rat brain.

This study examined the hypothesis that apoptotic inhibition via mitochondrial pathway was involved in hyperbaric oxygen preconditioning (HBO-PC)-induced neuroprotection on ischemia-reperfusion injury in rat brain. Male Sprague-Dawley rats (250 approximately 280 g, n=144) were divided into control, middle cerebral artery occlusion (MCAO) for 90 min, and HBO-PC plus MCAO groups. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at 12 h intervals for 2 days. At 24 h after the last HBO-PC, MCAO was performed and at 24 h after MCAO, neurological function, brain water content, infarct volume, and cell death were evaluated. Enzymatic activity of capase-3 and -9, and expression of cytochrome c, Bcl-2 and Bax proteins were performed in the samples from hippocampus, ischemic penumbra and core of the brain cortex, respectively. HBO-PC reduced brain edema, decreased infarction volume, and improved neurological recovery. HBO-PC reduced cytoplasm cytochrome c levels, decreased caspase enzyme activity, upregulated the ratio of Bcl-2 and Bax expression, and abated the apoptosis of ischemic tissue. HBO-PC protects brain tissues from ischemia-reperfusion injury by suppressing mitochondrial apoptotic pathways.

The role of IL-12 and TNF-alpha in AIDP and AMAN.

BACKGROUND: Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) have been described as two major subtypes of Guillain-Barré syndrome (GBS); however, the possible difference of their immune-inflammatory pathogenesis remains unclear. METHODS: In this study, by using FACS and enzyme-linked immunosorbent assays analyses, the role of Th1 cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12) and their receptors on peripheral blood mononuclear cells (PBMCs) and in serum concentrations were investigated in AIDP and AMAN. RESULTS: The results showed enhanced IL-12, IL-12R1 in AIDP and TNF-alpha in AMAN during the acute phase, as well as increased TNF-alpha and TNFR1 during the plateau phase of AIDP. Intravenous high dose immunoglobulin decreased IL-12R1 expression on cells in AIDP, but increased TNF-alpha and TNFR2 in AMAN. DISCUSSION: Our data suggest that IL-12 promotes disease development in AIDP and in contrast to previously inflammatory assumptions, TNF-alpha may play double roles in GBS. The anti-inflammatory role of TNF-alpha realized through TNFR2 in AMAN is possibly a therapeutic mechanism in the IVIg treatment of AMAN.

A population-based survey of multiple sclerosis in Shanghai, China.

OBJECTIVE: To conduct a large population-based survey on multiple sclerosis (MS) prevalence in Shanghai, China. METHODS: We established a network of physicians, mainly neurologists, for identifying prevalent patients with MS and systematically checked inpatient registers at each hospital in the study area for patients with a diagnosis of MS, neuromyelitis optica, or other demyelinating disorders. MS diagnosis in patients was validated by senior neurologists according to the McDonald criteria. RESULTS: In total, 123 patients with a validated MS diagnosis from the study population, 8.86 million inhabitants with permanent residence in Shanghai, were alive on the prevalence day. The crude MS prevalence rate was 1.39 cases per 100,000 inhabitants (95% CI: 1.16 to 1.66 cases) in the study population in Shanghai. There were 79 female and 44 male patients with MS, a female-to-male ratio of 1.8. Nearly all (96%) of the patients with validated MS had been examined by MRI. CONCLUSION: Multiple sclerosis prevalence in Shanghai is in line with that reported for other Asian populations.

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner.

Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-XL downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappaB inactivation by preventing NF-kappaB nuclear translocation and inducing IkappaBalpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.