Longitudinal association between Body mass index (BMI), BMI trajectories and the risk of frailty among older adults: A systematic review and meta-analysis of prospective cohort studies.

OBJECTIVE: We aimed to determine whether BMI categories and BMI trajectories were longitudinally associated with frailty in older adults via systematic review and meta-analysis of prospective cohort studies. METHOD: 3 databases (PubMed/MEDLINE, EMBASE and Web of Science) were systematically searched from inception to 8 September 2023. Two independent reviewers extracted data and appraised study quality. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data were pooled using random-effects models. RESULTS: 7 prospective cohort studies with 23043 participants were included in final BMI categories analyses, and 3 studies included BMI trajectory(23725 individuals). Compared with normal weight, we found a positive association between obesity (odds ratios(OR) = 1.74, 95 % confidence interval (CI): 1.21-2.51, P = 0.003), underweight (OR = 1.70, 95 % CI: 1.13-2.57, P = 0.011) and frailty in older adults. In middle age subgroup, compared with normal weight, OR of 2.21 (95 % CI: 1.44-3.38;I2 = 0 %) for overweight and OR of 5.20 (95 % CI: 2.56-10.55; I2 = 0 %) for obesity were significantly associated with frailty. In old age subgroup, compared with normal weight, only OR of 1.41 (95 % CI: 1.13-1.77; I2 = 65 %) for obesity was significantly associated with frailty. The results of BMI trajectories found that decreasing BMI (OR = 3.25, 95 % CI: 2.20-4.79, P < 0.0001) and consistently high BMI (OR = 3.66, 95 % CI: 2.03-6.61, P < 0.0001) increase the risk of frailty compared to consistently normal or overweight. CONCLUSION: Overweight and obesity in middle age were associated with significantly higher frailty in older adults, while obesity and underweight in old age were associated with relatively higher frailty in older adults. Early weight control may be beneficial for old age.

Inflammatory biomarkers of frailty: A review.

Frailty is a common geriatric syndrome characterized by increased vulnerability and is associated with adverse clinical events such as falls, hospitalization, and death. Early diagnosis and early intervention can delay or reverse frailty and ensure the healthy aging of older individuals. At present, there are no gold standard biomarkers for the diagnosis of frailty, which mainly relies on the scale to assess frailty, and the scale has shortcomings such as lagging assessment, subjectivity, and poor consistency. Frailty biomarkers help in early diagnosis and intervention in frailty. The purpose of this review is to summarize the existing inflammatory markers of frailty and focus on novel inflammatory biomarkers of frailty that can be used to help identify frailty early and explore potential intervention targets.

Impact of the Age of Cecal Material Transfer Donors on Alzheimer's Disease Pathology in 5xFAD Mice.

Alzheimer's disease is a progressive neurodegenerative disorder affecting around 30 million patients worldwide. The predominant sporadic variant remains enigmatic as the underlying cause has still not been identified. Since efficient therapeutic treatments are still lacking, the microbiome and its manipulation have been considered as a new, innovative approach. 5xFAD Alzheimer's disease model mice were subjected to one-time fecal material transfer after antibiotics-treatment using two types of inoculation: material derived from the caecum of age-matched (young) wild type mice or from middle aged, 1 year old (old) wild type mice. Mice were profiled after transfer for physiological parameters, microbiome, behavioral tasks, and amyloid deposition. A single time transfer of cecal material from the older donor group established an aged phenotype in the recipient animals as indicated by elevated cultivatable fecal Enterobacteriaceae and Lactobacillaceae representative bacteria, a decreased Firmicutes amount as assessed by qPCR, and by increased levels of serum LPS binding protein. While behavioral deficits were not accelerated, single brain regions (prefrontal cortex and dentate gyrus) showed higher plaque load after transfer of material from older animals. We could demonstrate that the age of the donor of cecal material might affect early pathological hallmarks of Alzheimer's disease. This could be relevant when considering new microbiome-based therapies for this devastating disorder.

Gastrectomy with omentum preservation versus gastrectomy with omentectomy for locally advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Omentectomy has been traditionally a part of standard radical gastrectomy. Its clinical benefit for locally advanced gastric cancer (LAGC) remains controversial. This study aimed at evaluating the impact of gastrectomy with omentum preservation (GOP) on survival, recurrence, surgical outcomes and postoperative complications by comparing with gastrectomy with omentum resection (GOR). METHODS: Original studies comparing GOP with GOR in LAGC were searched. Meta-analysis was performed using RevMan 5.4. RESULTS: Seven studies involving 1879 patients were analyzed. Compared with GOR, GOP achieved significantly better overall survival (HR = 0.75 [0.60, 0.95], P = 0.01), with similar relapse-free survival (HR = 0.84 [0.68, 1.03], P = 0.10). The two groups had similar total recurrence rate (OR = 0.86 [0.68, 1.08], P = 0.19) and no significant differences in rates of peritoneal, hematogenous, locoregional or distant lymph node recurrences. GOP had significantly less blood loss (MD = -83 [-139, -28] ml, P = 0.003) and tended to have shorter operation time (MD = -28 [-58, 2] min, P = 0.06), with similar harvested number of lymph nodes (MD = -0.4 [-2.6, 1.8], P = 0.70). The incidences of total all grade and major complications were similar in GOP and GOR (all grade: 31.8% vs. 30.3%, OR = 1.08 [0.79, 1.46], P = 0.64; major: 9.2% vs. 10.1%, OR = 1.14 [0.55, 2.34], P = 0.73). There were no significant differences in incidences of complication or postoperative mortality. CONCLUSIONS: Omentum preservation did not affect curability or survival in LAGC. These findings require validation in randomized controlled trials with large sample sizes.

Selective Targeting of Vascular Endothelial YAP Activity Blocks EndMT and Ameliorates Unilateral Ureteral Obstruction-Induced Kidney Fibrosis.

Kidney fibrosis is accompanied by vascular dysfunction. Discovering new ways to ameliorate dysfunctional angiogenesis may bypass kidney fibrosis. YAP (Yes-associated protein) plays a multifaceted role during angiogenesis. Here, we found that selectively targeting YAP signaling in the endothelium ameliorates unilateral ureteral obstruction (UUO)-induced kidney fibrosis. Genetic deletion of Yap1, encoding YAP protein, in VE-cadherin+ endothelial cells inhibited endothelial-to-mesenchymal transition (EndMT) and dysfunctional angiogenesis and improved obstructive nephropathy and kidney fibrosis. Treatment with the systemic YAP inhibitor verteporfin worsened kidney fibrosis symptoms because of its lack of cell specificity. In an attempt to identify endothelial-specific YAP modulators, we found that G-protein-coupled receptor coagulation factor II receptor-like 1 (F2RL1) was highly expressed in vessels after UUO-induced kidney fibrosis. The F2RL1 peptide antagonist FSLLRY-NH2 selectively blocked YAP activity in endothelial cells and ameliorated kidney fibrosis. Thus, selective antagonization of endothelial YAP activity might bypass kidney fibrosis and provide new avenues for the design of antifibrotic therapies.

Laparoscopic versus open transhiatal approach for adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Laparoscopic transhiatal approach (LTH) has gained growing popularity in the treatment of AEG. However, its safety and efficacy need to be evaluated. METHODS: Original studies comparing LTH with open transhiatal approach (OTH) were searched. Meta-analysis was performed using RevMan 5.3. RESULTS: Nine studies involving 2149 patients were eligible. Compared with OTH, LTH was associated with longer operation time (mean difference [MD] = 31min, 95%CI [20,41], P < 0.001) while less blood loss (MD = -103ml [-135, -72], P < 0.001), and harvested similar number of lymph nodes (MD = 0.1 [-1.2, 1.4], P = 0.89). There were no differences in time to ambulation (MD = -0.79 days [-1.77, 0.20], P = 0.12) or time to first flatus (MD = -0.82 days [-1.76, 0.11], P = 0.08); however, LTH was associated with shorter postoperative hospital stay (MD = -1.70 days [-2.34, -1.05], P < 0.001). The mortality after surgery was comparable for LTH and OTH (risk difference [RD] = -0.00 [-0.01, 0.01], P = 0.55). The incidence of total major complications was similar in LTH (6.1%) and OTH (8.4%) (RD = -0.02 [-0.05, 0.01], P = 0.12); there were no significant differences in the incidence of each complication. Furthermore, LTH achieved similar 2-year overall survival (OS) rate (risk ratio [RR] = 1.17 [0.86, 1.60], P = 0.31) while higher 5-year OS rate (RR = 1.43 [1.18, 1.73], P = 0.0003) and significant improvement of OS (univariable hazard ratio = 0.65 [0.50, 0.84], P = 0.0009; multivariable hazard ratio = 0.59 [0.44, 0.80], P = 0.0006). CONCLUSIONS: LTH is feasible and safe for AEG, and may provide more favorable short-term outcomes and potential long-term survival benefit, which needs to be confirmed by randomized trials.

Incidence of lymph node metastasis at each station in Siewert types â ¡/â ¢ adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis.

The optimal extent of lymphadenectomy for adenocarcinoma of the esophagogastric junction (AEG) has been continuously debatable. The study aimed to determine the incidence of lymph node metastasis at each station in Siewert types Ⅱ/Ⅲ AEG. PubMed was searched and publications reporting metastasis at each nodal station were eligible. Meta-analysis was performed using RevMan 5.3. Twenty-one studies involving 4662 patients were included. The incidence of lymph node metastasis was high (≥20%) in stations No. 3, 1, 2 and 7 in decreasing order, and moderate (10-20%) in stations No. 9, 19 and 110. The incidence did not exceed 10% in stations No. 10, 11p, 20, 8a, 4sa, 4 s b and 4d, was less than 5% in stations No. 5, 6, 11d, 12a, and even close to 0 in stations No. 107, 111 and 112. Compared with type Ⅲ tumors, type Ⅱ tumors had significantly lower incidence in some abdominal stations including No. 3, 4sa, 4 s b, 6, 8a and 10, while significantly higher in the lower mediastinal stations. The present analysis established a map of lymph node metastasis in Siewert types Ⅱ/Ⅲ AEG, which may serve as a valuable reference for the extent of lymphadenectomy.

Hippo/YAP Pathway Plays a Critical Role in Effect of GDNF Against Aß-Induced Inflammation in Microglial Cells.

Neuroinflammation is a critical mechanism responsible for the progression of Alzheimer's disease (AD). Recent studies reveal that Hippo/Yes-associated protein (YAP) signaling pathway is highly associated with a series of inflammation-related disorders. Glial cell line-derived neurotrophic factor (GDNF), with its neurotrophic and anti-apoptotic functions for nervous system, has been demonstrated to decrease the expression of proinflammatory mediators. Here we investigated whether Hippo/YAP signaling may affect amyloid-ß (Aß)-induced proinflammatory cytokine production in microglial cells and explored its relationship with the anti-inflammation function of GDNF. The results showed that Aß induced a decrease in the expression of YAP in microglia cells. YAP agonist XMU-MP-1 or its overexpression in microglial cells caused decreased expression of proinflammatory cytokines, whereas YAP antagonist Verteporfin or knockdown of YAP had the opposite effect. Treatment with GDNF resulted in upregulation of YAP expression and reduced the production of proinflammatory cytokines. Meanwhile YAP knockdown weakened the function of GDNF in microglial cells. In conclusion, Hippo/YAP pathway plays a critical role in effect of GDNF against Aß-induced inflammatory response in microglia. Targeting GDNF or Hippo/YAP signaling may be promising therapeutic approach for the treatment of AD.

Relationship between SUVmax in 18F-FDG PET/CT and PD-L1 expression in invasive lung adenocarcinoma / 中国胸心血管外科临床杂志

@#Objective    To investigate the relationship between the expression of programmed cell death ligand-1 (PD-L1) and the maximal standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the correlation of clinical factors between SUVmax values and PD-L1. Methods    The clinical data of 84 patients with invasive lung adenocarcinoma diagnosed pathologically in West China Hospital, Sichuan University from August 2016 to November 2018 were analyzed retrospectively, including 38 males and 46 females, aged 60 (32-85) years. The tumor was acinar-predominant in 37 patients, papillary in 20, lepidic in 19, solid in 5 and micropapillary in 3. Multivariate analysis of the relationship between SUVmax value and other clinicopathological features was performed by linear regression. Logistic regression analysis was used to analyze the relationship between PD-L1 protein expression and other pathological features. Results    The SUVmax of the PD-L1 expression group was significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group (P=0.002) and intermediate-grade histologic subtype (P=0.016). The SUVmax cut-off value of PD-L1 expression in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype was 5.34 (AUC: 0.732, P=0.002) and 5.34 (AUC: 0.720, P=0.017), respectively. Multivariate analysis showed that pleura involvement, vascular tumor thrombus and the increase of tumor diameter could cause the increase of the SUVmax value, while the SUVmax value decreased in the moderately differentiated tumor compared with the poorly differentiated tumor. The SUVmax cut-off value between low-grade histologic subtype and intermediate-grade histologic subtype, intermediate-grade histologic subtype and high-grade histologic subtypes was 1.54 (AUC: 0.854, P<0.001) and 5.79 (AUC: 0.889, P<0.001), respectively. Multivariate analysis of PD-L1 expression showed pleura involvement (P=0.021, OR=0.022, 95%CI 0.001 to 0.558) and moderate differentiation (opposite to poor differentiation) (P=0.004, OR=0.053, 95%CI 0.007 to 0.042) decreased the expression of PD-L1. Conclusion    The SUVmax of the PD-L1 expression group is significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype. The level of SUVmax and the expression of PD-L1 in invasive lung adenocarcinoma are related to many clinical factors.

MicroRNA 375 modulates hyperglycemia-induced enteric glial cell apoptosis and Diabetes-induced gastrointestinal dysfunction by targeting Pdk1 and repressing PI3K/Akt pathway.

Diabetic neuropathy can damage systemic nervous system, including alteration of enteric nervous system and subsequent gastrointestinal dysfunction. The effect of diabetes on enteric glia cell (EGC) is not clear. We investigated the effect of diabetes and hyperglycemia on EGC, and the role of microRNA375 in modulating EGC survival in vivo and in vitro. Streptozotocin-induced diabetic mice were intraperitoneally injected with microRNA375 inhibitor or its negative control. EGC was transfected with microRNA375 inhibitor or its mimic. Diabetes mice with gastrointestinal dysfunction showed increased apoptosis of EGC (no difference in cell numbers) and gene expression of micorRNA375 in the myenteric plexus. Hyperglycemia triggered apoptosis of EGC in vitro with decreased expression of Pdk1 and p-Akt, but increased expression of micorRNA375. MicorRNA375 mimic induced apoptosis of EGC in vitro with repressed Pdk1and p-Akt. MicorRNA375 inhibitor could both prevent hyperglycemia-induced apoptosis of EGC in vitro and diabetes-induced gastrointestinal dysfunction in vivo. Our results suggest that diabetes-induced gastrointestinal dysfunction is related to increased apoptosis of EGC in the myenteric plexus. Hyperglycemia can increase the expression of microRNA375 and damage EGC survival through PI3K/Akt pathway. MicroRNA375 specific inhibition can prevent hyperglycemia induced EGC damage and diabetes-induced gastrointestinal dysfunction.

Effect of PLCε gene silencing on inhibiting the cancerous transformation of ulcerative colitis.

The aim of the present study was to investigate the effect of phosphoinositide-specific phospholipase Cε (PLCε) gene silencing on the inhibition of cancer development in ulcerative colitis (UC) and to explore the pathogenesis and carcinogenic mechanism of UC, in order to facilitate the establishment of novel strategies for the treatment of UC, prevent the cancerous transformation of UC and discern the association between inflammation and cancer. A pGenesil-PLCε RNA interference vector was constructed and transfected into HEK293 cells (pGenesil-PLCε group). HEK293 cells transfected with pGenesil empty plasmid were set as the negative control (pGenesil-NC group). The expression of PLCε was observed, and molecules associated with the PLC signaling pathway were detected using a reverse transcription-quantitative polymerase chain reaction and western blotting. ELISA was used to determine the expression of serum interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) of mice in which the PLCε gene had been silenced. Compared with the pGenesil-NC group, the mRNA and protein levels of PLCε were significantly decreased in the pGenesil-PLCε group. In addition, the mRNA levels of K-ras, NF-κB, Fas and Bcl-2 were markedly reduced, while P53 mRNA level was notably enhanced, in the pGenesil-PLCε group, and these changes were accompanied by similar changes in the corresponding protein levels. The serum IL-1 and TNF-α expression in the PLCε gene-silenced mice was significantly reduced compared with that in the control mice. In conclusion, PLCε RNA silencing can effectively inhibit the cancerous transformation of UC by regulating the colorectal cancer-related cell proliferation and cell cycle in vivo. In addition, PLCε RNA silencing can suppress the expression of inflammatory factors in vitro.

Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis.

It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83-1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70-1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56-0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1-4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3-4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1-4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3-4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1-4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [-0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = -0.02, 95% CI [-0.05, -0.00], P = 0.04), as well as less all grade 1-4 and grade 3-4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non-Asian trials. Lower incidence of grade 1-4 nausea, diarrhea, mucositis, grade 3-4 mucositis, increased creatinine, and decreased calculated creatinine clearance was observed in S-1-containing regimens.S-1 could not improve OS, but increase some hematological toxicities in Asian patients. Therefore, special attention on hematological toxicities should be paid to Asian patients because S-1 is administered on an outpatient basis.

[Role of p38 mitogen-activated protein kinase pathway in pathogenesis of ulcerative colitis].

OBJECTIVE: To elucidate the role of p38 mitogen-activated protein kinase (p38MAPK) in the pathogenesis of ulcerative colitis (UC) and DSS-induced colitis in mice. METHODS: (1) 27 Balb/c mice were divided randomly into three groups: DSS-induced colitis group, normal control group and SB203580 treatment group. In DSS-induced colitis group, mice were feed with 5% DSS solution. In SB203580 treatment group, mice were feed with 5%DSS solution for 72 hours, then treated with intraperitoneal injection of SB203580 (1 mg/kg) once daily. Disease activity index (DAI) was record to evaluate the severity of colitis. The mice were executed after 7 days. The levels of TNF-alpha and IL-1beta were measured by ELISA. (2) A total of 54 cases were included in the study. 36 cases were patients with active ulcerative colitis, 18 cases were normal mucosa from 18 colon cancer cases served as control. Effects of SB203580 (a selective p38MAPK inhibitor) on expression of TNF-alpha and IL-1beta in intestinal mucosal biopsy specimens from patients with ulcerative colitis were determined on condition of tissue culture. RESULTS: (1) The DAI scores, the levels of TNF-alpha and IL-1beta in SB203580 group were lower significantly compared with DSS group (P < 0.05), and were increased significantly compared with normal control group (P < 0.05). (2) The levels of TNF-alpha and IL-1beta in intestinal mucosal biopsy specimens in SB203580 treatment group were lower significantly than those in UC group (P < 0.05). CONCLUSION: SB203580 can inhibit p38MAPK signal transduction pathway, then reduce the expression of pro-inflammatory cytokine TNF-alpha and IL-1beta.

Laparoscopic splenectomy with or without devascularization of the stomach for liver cirrhosis and portal hypertension: a systematic review.

BACKGROUND: Open splenectomy and devascularization are effective treatments for cirrhotic patients with severe thrombocytopenia and variceal bleeding. However, it remains controversial whether laparoscopic splenectomy (LS) and devascularization (LSD) can be indicated and beneficial in these patients. OBJECTIVES: A systematic review of the efficacy and safety of LS and LSD for patients with liver cirrhosis and portal hypertension was undertaken to clarify controversy about their utilization in such patients. METHODS: A systematic search strategy was performed to retrieve relevant studies from PubMed and Embase.com. The literature search and data extraction were independently performed by two reviewers. RESULTS: Sixteen articles met the inclusion criteria. The methodology of the identified articles was poor. Six hundred and fifty-one patients, including 478 LS patients and 173 LSD patients, were involved in efficacy and safety evaluations. There was wide variability in the outcome measures between studies. There was only one death in the patients underwent LSD. Reported major complications included post-operative bleeding requiring re-surgery, pancreatic leakage and gastric perforation. Seven studies were identified with comparisons between laparoscopic and open procedures. No meta-analysis was possible because of heterogeneity between studies and lack of randomization. CONCLUSIONS: The publications reviewed revealed LS and LSD to be safe and effective in the setting of liver cirrhosis and portal hypertension. From the comparison articles, laparoscopic procedures appear to be superior to open procedures regarding blood loss, hospital stay, complication rate and liver function impairment. However, it is difficult to draw firm statistical conclusions due to lack of high-quality evidence.

Tetrandrine attenuates spatial memory impairment and hippocampal neuroinflammation via inhibiting NF-κB activation in a rat model of Alzheimer's disease induced by amyloid-ß(1-42).

BACKGROUND: The neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of nuclear factor-κB (NF-κB) activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of AD. MATERIALS AND METHODS: Tetrandrine was administered in a rat model of AD induced by amyloid-ß (Aß)(1-42). The learning and memory impairment was examined using Morris water maze; the extent of histological injury in hippocampus was determined by Nissl staining; NF-κB DNA binding activity was assessed by electrophoretic mobility shift assay; the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß was measured by enzyme-linked immunosorbent assay. RESULTS: A significant improvement was observed in learning and memory impairment in rats with tetrandrine, and the increase in NF-κB DNA binding activity, the over-expression in IL-1ß and TNF-α as well as the increased histological injury in hippocampus in rats induced by Aß(1-42) were significantly reduced following administration of tetrandrine. CONCLUSION: Tetrandrine could significantly ameliorate Aß(1-42)-induced spatial learning and memory impairment, and the beneficial effect of tetrandrine treatment could be linked, at least in part, to the inhibition of NF-κB activity and the downregulation of expression of IL-1ß and TNF-α, suggesting that administration of tetrandrine may provide a therapeutic approach for AD.

[Protective effects of emodin on intestinal lesion in rat model with acute necrotizing pancreatitis].

OBJECTIVE: To explore the protective effects and mechanism of Emodin on intestinal lesion in the rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty SD rats were randomly divided into 3 groups: sham-operated (SO) group, ANP group and Emodin-treated group. ANP was induced by retro-pumping 3.5% sodium cholate to pancreaticobiliary duct. 5.5 hours after modeling, phenol red, which was employed to measure intestinal transit, was injected to duodenum. 0.5 hour later, rats were sacrificed to collect intestine for the results of intestinal transit and other tests of intestine. Furthermore, intestinal tissue (HE staining) was observed by light microscope, and the activity of nuclear factor-kappa B (NF-kappaB) in intestine was detected by immunohistochemical method. The content of intestinal tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was detected with the method of enzyme-labeled immunosorbent assay (ELISA). RESULTS: Compared with SO group, there was significantly decrease of intestinal transit in ANG group (P < 0.05). Furthermore, intestinal transit in Emodin-treated group significantly increased when compared with ANP group (P < 0.05). NF-kappaB p65 positive rate of intestinal cell nuclei, content of intestinal TNF-alpha and IL-1beta in ANP group were obviously higher than those in SO group (P < 0.05). After the treatment of Emodin, NF-kappaB p65 positive rate of intestinal cell nuclei, content of TNF-alpha and IL-1beta were decreased (P < 0.05). Moreover, there was a negative correlation between intestinal transit and content of TNF-alpha, IL-1beta, with correlation coefficients--0.83, -0.76, respectively (P < 0.05). CONCLUSION: Emodin could increase intestinal transit, suppress the activity of NF-kappaB in intestine, decrease the content of intestinal TNF-alpha and IL-1beta, and attenuate the pathological damage of intestine.

[Influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in patients with severe acute pancreatitis: a randomized controlled trial].

BACKGROUND: Resistin level is high in patients with severe acute pancreatitis (SAP), and resistin is expected to be a new marker for evaluating the severity of acute pancreatitis. OBJECTIVE: To explore the influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in SAP patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Twenty-eight SAP patients meeting inclusion criteria from Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University were included, and the patients were randomly divided into treatment group and placebo group. There were 13 patients in the treatment group and 15 patients in the placebo group. Patients in the treatment group were given traditional Chinese herbal medicine in addition to the conventional treatment. Patients in the placebo group were given placebo in addition to the conventional treatment. MAIN OUTCOME MEASURES: The serum resistin levels on admission, and days 1, 3, 5, and 7 after the admission were detected. RESULTS: The serum resistin levels on admission in all the patients were higher than normal level, and there was no significant difference between the two groups (P>0.05). On days 1, 3, 5, and 7 after admission, the resistin levels in the treatment group were (3.29 + or - 1.66) microg/L, (3.71 + or - 1.05) microg/L, (3.08 + or - 1.47) microg/L and (3.62 + or - 1.67) microg/L, and in the control group (5.16 + or - 1.93) microg/L, (5.07 + or - 1.53) microg/L, (4.88 + or - 1.47) microg/L and (5.12 + or - 1.48) microg/L, respectively. The resistin levels were lower in the treatment group than in the control group (P<0.05). CONCLUSION: Serum resistin level in SAP patients can be decreased by integrated traditional Chinese medicine and Western medicine therapy.

[Risk factors and infection characteristics of secondary pancreatic infection in severe acute pancreatitis].

OBJECTIVE: To explore risk factors and infection characteristics of secondary pancreatic infection in severe acute pancreatitis (SAP). METHODS: A clinical data of 49 patients with secondary pancreatic infection in severe acute pancreatitis (SPI group)were matched with 49 patients without infection in severe acute pancreatitis (NSPI group) between January 2003 and December 2005. The two groups were analyzed by a case-control study. Conditional Logistic regression model univariate and multivariate were used to screen out risk factors. The types of infection, the peak infection and the bacteria spectrum were analyzed in SPI group. RESULTS: (1) In univariate Logistic regression analysis, 7 factors including continuous hypoalbuminemia, prolonged time of central venous catheter, usage of hormone, high APACHE II scores, multi-antibiotics, intestine dysfunction and continuous hyperglycemia were selected out. Moreover, the first three were statistically significant in multivariate Logistic regression analysis. (2) Pancreatic abscess ranked first in SPI group. Of all the pancreatic infection, 22.5% occurred within two weeks and 71.4% occurred in the 4th week or later. (3) In SPI group, 81 strains of microorganisms were cultured, including 45 strains of gram-negative bacteria (55.6%), 22 strains of gram-positive bacteria (27.2%), and 14 strains of fungi (17.3%). The common gram-negative bacteria were Escherichia coli, and the common gram-positive bacteria were Staphylococci and Enterococci. The fungi included Monilia and Yeastoid fungus. Further study revealed that 35 strains of all the microorganisms were intestinal bacteria (43.2%). CONCLUSIONS: Continuous hypoalbuminemia, prolonged time of central venous catheter and usage of hormone were independent risk factors of SPI. The main type of infection was pancreatic abscess. Gram-negative bacteria, were the common bacteria causing secondary pancreatic infection.

[Risk factor analysis of severe acute pancreatitis complicated by pancreatic encephalopathy].

OBJECTIVE: To study the risk factors for severe acute pancreatitis (SAP) complicated by pancreatic encephalopathy (PE). METHODS: Clinical data from 255 patients with SAP from January 2005 to December 2006 were reviewed. Thirty-one SAP patients had PE, and 224 SAP patients did not. Clinical characteristics of SAP patients in both PE group and non-PE group were analyzed. RESULTS: Ranson scale and the incidence rates of acute respiratory distress syndrome (ARDS), renal failure, hypoproteinemia, hypocalcemia and hyperglycosemia in PE group were higher than those in non-PE group (P<0.05). There were no significant differences in acute physiology and chronic health evaluation II and CT severity index scales, the activities of amylase and lipase, the incidence rate of liver function failure, the infection rate and the operability between the PE group and the non-PE group (P>0.05). Multivariate logistic regression analysis showed that ARDS and hyperglycosemia were high risk factors. Cure rate in PE group was higher than that in non-PE group. CONCLUSION: Nosogenesis of PE is the result of multiple factors. ARDS and hyperglycosemia may be the high risk factors for PE.