Asymptomatic spinal lesions in patients with AQP4-IgG-positive NMOSD: A real-world cohort study.

OBJECTIVE: This study aims to explore the frequency and influencing factors of asymptomatic spinal lesions (ASLs) and their impact on subsequent relapses in patients with AQP4-IgG-positive NMOSD (AQP4-NMOSD) in a real-world setting. METHODS: We retrospectively reviewed clinical information and spinal MRI data from AQP4-NMOSD patients who had at least one spinal cord MRI during their follow-ups. Kaplan-Meier curves and Cox proportional hazards models were employed to ascertain potential predictors of remission ASLs and to investigate factors associated with subsequent relapses. RESULTS: In this study, we included 129 patients with AQP4-NMOSD and reviewed 173 spinal MRIs during attacks and 89 spinal MRIs during remission. Among these, 6 ASLs (3.5%) were identified during acute attacks, while 8 ASLs (9%) were found during remission. Remission ASLs were linked to the use of immunosuppressive agents, particularly conventional ones, whereas no patients using rituximab developed ASLs (p = 0.005). Kaplan-Meier curve analysis indicated that patients with ASLs had a significantly higher relapse risk (HR = 4.658, 95% CI: 1.519-14.285, p = 0.007) compared to those without. Additionally, the use of mycophenolate mofetil (HR = 0.027, 95% CI: 0.003-0.260, p = 0.002) and rituximab (HR = 0.035, 95% CI: 0.006-0.203, p < 0.001) significantly reduced the relapse risk. However, after accounting for other factors, the presence of ASLs did not exhibit a significant impact on subsequent relapses (HR = 2.297, 95% CI: 0.652-8.085, p = 0.195). INTERPRETATION: ASLs may be observed in patients with AQP4-NMOSD. The presence of ASLs may signify an underlying inflammatory activity due to insufficient immunotherapy. The administration of immunosuppressive agents plays a key role in the presence of remission ASLs and the likelihood of subsequent relapses.

Mechanical digit sensory stimulation: a randomized control trial on neurological and motor recovery in acute stroke.

Background: Mechanical digit sensory stimulation (MDSS) is a novel therapy designed to accelerate the recovery of upper limb (including hand) function in patients with hemiplegia following a stroke. The primary goal of this study was to investigate the effect of MDSS on patients with acute ischemic stroke (AIS). Methods: Sixty-one inpatients with AIS were randomly divided into conventional rehabilitation group (RG) and stimulation group (SG), and the latter group received MDSS therapy. A healthy group consisting of 30 healthy adults was also included. The interleukin-17A (IL-17A), vascular endothelial growth factor A (VEGF-A), and tumor necrosis factor-alpha (TNF-α) plasma levels were measured in all subjects. The neurological and motor functions of patients were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), Fugel-Meyer Assessment (FMA), and Modified Barthel Index (MBI). Results: After 12 days of intervention, the IL-17A, TNF-α, and NIHSS levels were significantly decreased, while the VEGF-A, MMSE, FMA, and MBI levels were significantly increased in both disease groups. No significant difference was observed between both disease groups after intervention. The levels of IL-17A and TNF-α were positively correlated with NIHSS but negatively correlated with MMSE, FMA, and MBI. The VEGF-A levels were negatively correlated with NIHSS but positively correlated with MMSE, FMA, and MBI. Conclusion: Both MDSS and conventional rehabilitation significantly reduce the production of IL-17A and TNF-α, increase the VEGF-A levels, and effectively improve cognition and motor function of hemiplegic patients with AIS, and the effects of MDSS and conventional rehabilitation are comparable.

Changes and roles of IL-17A, VEGF-A and TNF-α in patients with cerebral infarction during the acute phase and early stage of recovery.

BACKGROUND AND PURPOSE: Interleukin 17A (IL-17A), vascular endothelial growth factor A (VEGF-A) and tumour necrosis factor alpha (TNF-α) are important cytokines detected mostly within two weeks after stroke in previous clinical studies. Longer clinical studies investigating these cytokines are lacking. We aimed to explore the roles of these cytokines in patients within 35 days after cerebral infarction. METHODS: Thirty patients with cerebral infarction and 30 healthy individuals were enrolled. Venous blood was collected from each patient at specific times and from each healthy individual only once. Coma and neurological functional deficits of the patients were evaluated by the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS), respectively. Three cytokines were measured. The correlations among the three cytokines and between each cytokine and the GCS/NIHSS scores were analysed. RESULTS: IL-17A and TNF-α began to increase on day 1 after cerebral infarction, peaked on day 4, then decreased, and increased again on day 18. IL-17A returned to normal on day 35, but TNF-α remained higher than normal on day 35. VEGF-A began to increase on day 1, peaked on day 7, and returned to normal on day 35. From days 18 to 35, IL-17A was positively correlated with the GCS scores, and both IL-17A and VEGF-A were negatively correlated with the NIHSS scores. CONCLUSION: After cerebral infarction, VEGF-A from the acute phase and IL-17A from the early stage of recovery may be important for nerve protection and repair; TNF-α plays a complex role within 35 days.

Clinicopathological Prognostic Factors and Chemotherapeutic Outcome for Two Histopathological Types of Ampulla of Vater Adenocarcinoma.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AAV) is standardly treated using a complex operation, a pancreatoduodenectomy (PD), to remove the tumor. However, dicision-making in AAV clinical treatment remains difficult due to the broad range of AAV types, outcomes, and responses to special chemotherapeutics. Thus, this study aimed to explore clinicopathological prognostic factors associated with overall survival, as well as post-chemotherapeutic effects related to curative resection of AAV. METHODS: We retrospectively reviewed data for clinicopathological outcome of 47 patients diagnosed with AAV that had underwent a PD. Overall survival probabilities were obtained using the Kaplan-Meier estimate method and a Cox proportional hazards model. RESULTS: Forty-five patients underwent LPD (laparoscopic pancreatoduodenectomy) and two patients underwent PD. The patient group was composed of 31 males (66%) and 16 females (34%) with a mean age of 65(34-91)years. We selected 45 patients for long-term survival analysis. One- and three-year overall survival rates after resection were 97.6% and 58.9% respectively. The median survival was 37.7 months for the intestinal-type and 26.9 months in pancreatobiliary-type ampullary tumors. Serum carbohydrate antigen (CA) 19-9 greater than 37 U/ml (HR 0.140, P = 0.007), perineural invasion (HR 0.141, P = 0.003), and classification as pancreatobiliary-type (HR 6.633, P = 0.006) were independently associated with poor survival. Serum carcinoembryonic antigen (CEA) greater than 5 µg/ml (P = 0.031), serum CA 19-9 greater than 37 U/ml (P = 0.002), tumor sizes greater than 2.5cm (P=0.002), and positive perineural invasion (P=0.003) were all associated with a poor prognosis in the histopathological subgroup. Serum CA 19-9 greater than 37 U/ml (P=0.002) and positive perineural invasion (P=0.001) were significantly associated with poor survival in of patients with intestinal-type ampullary tumors. Serum CEA greater than 5 µg/ml (P=0.013) and tumor sizes greater than 2.5cm (P=0.002) were significantly associated with poor survival in patients with pancreatobiliary-type ampullary tumors. CONCLUSIONS: Pancreatobiliary-type ampullary tumors were associated with poor survival. Serum CA 19-9 in the intestinal-type and CEA in the pancreatobiliary-type were significantly associated with poor survival. Ajuvant chemotherapy could not predict the survival of AAV patients.

Optimal Laparoscopic Management and Oncological Outcomes of Gastrointestinal Stromal Tumors in Duodenum: Pancreaticoduodenectomy or Pancreas-Sparing Duodenectomy?

BACKGROUND: Gastrointestinal stromal tumors (GIST) of the duodenum are rarely reported and optimal minimally invasive management has not been well proposed. Pancreaticoduodenectomy and different types of pancreas-sparing duodenectomy can be chosen; however, which to choose and its corresponding clinical outcomes and oncological concerns remain controversial. PATIENTS AND METHODS: Patients diagnosed with GIST of duodenum underwent laparoscopic pancreaticoduodenectomy (L-PD) or pancreas-sparing duodenectomy (L-PSD) in Zhejiang Provincial People's Hospital were enrolled. All prospectively maintained data were analyzed retrospectively. Patients were grouped into the L-PD group or the L-PSD group, and the clinical outcomes and oncological outcomes were analyzed. RESULTS: Between June 2013 and March 2019, a total of 22 patients (11 males/11 females) underwent surgical management, including 13 L-PDs and 9 L-PSDs. The average age was 58.2±9.5 year-old (median 60.5 year-old). The most common presentations were GI bleeding (54.5%) and abdominal discomfort (27.2%), and the dominant lesion located in the second portion of duodenum (59.1%). Compared with L-PD group, L-PSD group showed much shorter operation time (364.2±58.7min vs. 230.0±12.3min, P<0.001), less blood loss (176.9±85.7mL vs. 61.1±18.2min, P<0.001), faster recovery to off-bed (2.6±1.3d vs. 1.1±0.3d, P=0.003), anus flatus (4.5±1.0d vs. 2.4±0.5d, P<0.001) and liquid intake (4.9±1.3d vs. 2.3±0.5d, P<0.001). Lymph node retrieval was much less in L-PSD, but no lymph node metastasis was observed in any patients. L-PSD had much Lower morbidity of both minor (Grade I/II) and major (III/IV/V) complications than that of L-PD (11.1% vs. 61.6%, P=0.02), resulting in shorter hospital stays (10.9±3.8d vs. 20.6±11.1d, P=0.021) and less total cost (76,972.4±11,614.8yuan vs 125,628.7±46,356.8yuan, P=0.006). The median follow-up was 42 months (range from 12 to 82months) without loss. Only 1 L-PD patient suffered hepatic metastasis 36months after surgery, and given sunitinib to stabilize the disease, none of the rest observed recurrence or metastasis. CONCLUSION: For GIST located opposite the major papilla, L-PSD showed comparable safety and oncological benefits when compared to L-PD, with shorter operation time, less blood loss and much faster recovery time, resulting in much less total cost. L-PSD should be applied in selected patients with experienced hands.

Protective effect of glycyrrhizic acid on cerebral ischemia/reperfusion injury via inhibiting HMGB1-mediated TLR4/NF-κB pathway.

Cerebral ischemia is caused by various disorders, such as stroke, myocardial infarction, or peripheral vascular disease. The purpose of this paper was to investigate the effects of glycyrrhizic acid (GA) on cerebral ischemia/reperfusion (I/R) injury. Middle cerebral artery occlusion was established to evaluate the effects of GA on cerebral ischemia. In this study, our results showed that GA could dramatically decrease cerebral edema, reduce the neurological deficits, and smaller brain infarct volume was found in the GA treatment group. In serum and brain tissue, GA also increased superoxide dismutase activity. In addition, in serum and brain tissue, GA also dramatically inhibited the secretion of inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α. Moreover, GA inhibited the expressions of high-mobility group protein box-1 (HMGB1)-mediated TLR4/NF-κB pathway. Our data determined that GA may provide protective effect on the I/R-induced cerebral ischemia disease.

Mini-subvastus versus medial parapatellar approach for total knee arthroplasty: a prospective randomized controlled study.

PURPOSE: Whether minimally invasive total knee arthroplasty (MIS-TKA) could offer better and faster recovery without the deviation of post-operative prosthesis position and limb alignment is still controversial. This prospective and randomized study was conducted to compare the clinical and radiological outcomes between patients who underwent the mini-subvastus approach of MIS-TKA and those who underwent the medial parapatellar approach of traditional TKA. METHODS: Fifty patients, including 50 knees, who required TKA due to osteoarthritis were randomized to the mini-subvastus group (group I) or the medial parapatellar group (group II). All patients accepted the same method of anaesthesia, equal support therapy and identical rehabilitation exercise after surgery. The evaluation system included operation time, tourniquet time, blood loss, skin incision length in flexion, straight leg raising time, the time of lower limb muscle strength up to grade 4, the time of walking with aid or without aid, the time of walking up and down the stairs, the active flexion angle, range of movement (ROM), the Knee Society Scores (KSS), visual analogue score for pain (VAS), hospital stays and radiographic outcomes. RESULTS: The mini-subvastus approach offered smaller skin incision length in flexion, but at the cost of operation time (P < 0.001). No significant difference was found in tourniquet time and blood loss. The patients in group I could achieve straight leg raising, the lower limb muscle strength up to grade 4, walking with or without aid, and walking up and down the stairs earlier (P < 0.001). The active flexion angle, ROM, VAS and KSS in group I were superior to those in group II until six months post-operatively (P < 0.001), but the differences was not apparent at 12 months post-operatively. More importantly, there was no significant difference between the two groups on radiological outcomes (P > 0.05). CONCLUSIONS: The mini-subvastus approach could offer faster recovery, less pain and shorter hospital stays without compromising the principles of proper prosthesis position and limb alignment compared with the medial parapatellar approach.

Relationship of microRNA 616 gene polymorphism with prognosis of patients with premature coronary artery disease.

OBJECTIVE: To investigate the relationship of microRNA 616 (has-miR-616) single nucleotide polymorphisms (SNPs) and its target gene paraoxonase 1 (PON 1) with the prognosis of patients with premature coronary artery disease (pCAD). METHODS: 266 pCAD cases in the case group and 300 cases in the control group were collected. Using the polymorphism method of polymerase chain reaction and restriction fragment length, the has-miR-616 rs3735590 genotypes of target gene PON 1 were detected. RESULTS: In the changes of rs3735590 C/T SNPs, compared with CC genotypes, the risk of coronary heart disease of the individuals carrying CT and TT genotypes were reduced by 42% and 31%, respectively (p < 0.05). The risk of developing coronary heart disease in individuals carrying CT and TT genotypes were reduced significantly in the population with levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. CONCLUSION: Target gene PON 1 of hsa-miRNA-616 rs3735590C-T SNPs is associated with the reduced incidence risk of pCAD, and carrying C alleles is an independent risk factor for pCAD.

Effects of monocyte-endothelium interactions on the expression of type IV collagenases in monocytes.

The adhesion of monocytes to endothelial cells is one of the early stages in the development of atherosclerosis. The expression of type IV collagenases, which include matrix metalloproteinase (MMP)-2 and MMP-9, in monocytes is hypothesized to play an important role in monocyte infiltration and transformation into foam cells. The aim of the present study was to examine the effects of monocyte-endothelium interactions on the expression levels of type IV collagenases and their specific inhibitors in monocytes, and to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in this process. Monocytes were single-cultured or co-cultured with endothelial cells. The expression of the type IV collagenases, MMP-2 and MMP-9, and their specific inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, in monocytes was determined by immunohistochemistry followed by image analysis. The expression levels of MMP-2 and MMP-9 were found to be low in the single-culture monocytes, but increased significantly when the monocytes and endothelial cells were co-cultured. However, treatment with monoclonal TNF-α or IL-1ß antibodies partially inhibited the upregulated expression of MMP-2 and MMP-9 in the co-cultured monocytes. Expression of TIMP-1 and TIMP-2 was observed in the single monocyte culture, and a small increase in the expression levels was observed when the monocytes were co-cultured with endothelial cells. Therefore, monocyte-endothlium interactions were shown to increase the expression of type IV collagenases in monocytes, resulting in the loss of balance between MMP-2 and -9 with TIMP-1 and -2. In addition, TNF-α and IL-1ß were demonstrated to play important roles in this process.

PI3K/AKT signaling pathway plays a role in enhancement of eNOS activity by recombinant human angiotensin converting enzyme 2 in human umbilical vein endothelial cells.

The aim of this study was to investigate the effect of PI3K/AKT signaling pathway in the activity of recombinant human angiotensin converting enzyme 2 (rhACE2) promoted the activity of endothelial nitric oxide synthase (eNOS). The human umbilical vein endothelial cells (HUVEC) were cultured in vitro. Then treated with Ang II (1×10(-6) mol/L) for 24 h. The rhACE2 (100 µmol/L) was added and incubated for 5, 10, 15, 30, 60 min respectively which was based on Ang II intervention. The effect of rhACE2 on phosphorylation eNOS level was also observed in the presence of LY294002 (10 µmol/L) (PI3K/AKT inhibitors). Griess reagent method was applied to measure NO contents in cell culture supernatant, RT-PCR to detect the expression of eNOSmRNA in HUVEC, and Western blot to detect the expression of eNOS and phosphorylated eNOS. In Ang II intervention group, NO contents were significantly lower than control group (P < 0.05). Through rhACE2 treatment, the NO contents in cell culture medium and the expression level of phosphorylated eNOS were significantly higher than in Ang II intervention group (P < 0.05), but eNOSmRNA and non-phosphorylated eNOS protein expression level showed no significant difference (P > 0.05). After HUVEC was intervened by PI3K/AKT pathway inhibitor LY294002, the expression level of phosphorylated eNOS was significantly lower than that in the rhACE2 30 min treatment group (P < 0.05). rhACE2 may reduce the activity of Ang II inhibited endothelial cell eNOS, which can be blocked by PI3K/AKT pathway inhibitor LY294002, suggesting PI3K/AKT signaling pathway plays an important role in rhACE2's promotion of the activity of endothelial cell eNOS.

Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting.

BACKGROUND: Atrial arrhythmia (AA) is the most common complication after coronary artery bypass grafting (CABG). Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG. METHODS: We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible. RESULTS: Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.86-1.47, P = 0.40). Magnesium in addition to beta-blocker did not significantly affect LOS (weighted mean difference -0.14 days of stay, 95% CI -0.58 to 0.29, P = 0.24) or the overall mortality (OR 0.59, 95% CI 0.08-4.56, P = 0.62). However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone (OR 2.80, 95% CI 1.66-4.71, P = 0.0001). CONCLUSIONS: This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium.

Computed tomography for detecting left atrial thrombus: a meta-analysis.

INTRODUCTION: Thromboembolism, usually originating from the left atrium (LA) and left atrial appendage (LAA), is a major complication of atrial fibrillation and may result in transient ischemic attack and stroke. Computed tomography (CT) is a noninvasive test for detection of LA and LAA thrombus. We sought to conduct a meta-analysis to evaluate the accuracy of CT in detecting LA/LAA thrombus. MATERIAL AND METHODS: The PubMed, Medline, ISI Web of Knowledge and Cochrane Library databases up to June 2012 were searched for studies comparing CT and transesophageal echocardiography as the reference standard in detecting LA/LAA thrombus. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC) curves. RESULTS: A total of 9 studies with 1646 patients were included in this meta-analysis. The publication years spanned from 2007 to 2012. For CT diagnosis of LA/LAA thrombus, the mean sensitivity and specificity were 81% (95% CI: 70-90%) and 90% (95% CI: 88-91%), respectively. The SROC analysis showed an area under the curve of 0.93. CONCLUSIONS: Computed tomography shows a good diagnostic accuracy in detecting LA/LAA thrombus with high sensitivity and specificity. Thus CT should be considered the foremost noninvasive alternative to transesophageal echocardiography for detecting LA/LAA thrombus. Randomized studies at the patient level are needed to address the potential use of CT in detecting LA/LAA thrombus.

Enhanced chemosensitivity of drug-resistant osteosarcoma cells by lentivirus-mediated Bcl-2 silencing.

The Bcl-2 gene is frequently overexpressed in malignancy and is responsible for the resistance induced by chemotherapeutic drugs. The aim of this study was to investigate whether the inhibition of Bcl-2 by lentivirus-mediated RNA interference would enhance doxorubicin cytotoxicity in the drug-resistant human osteosarcoma MG63 cells. Downregulation of Bcl-2 was confirmed by quantitative reverse transcription PCR and Western blotting. Moreover, the ratio of Bcl-2/Bax decreased due to the downregulation of Bcl-2 expression and the upregulation of Bax expression. Decreased cyclin D1 expression was also detected. Flow cytometry and MTT assays revealed that Bcl-2 knock-down increased cellular apoptosis and the MG63 cells became sensitive to doxorubicin. However, no detectable alterations in MDR1 or Bcl-xl expression were observed. Therefore, lentivirus-mediated Bcl-2 knock-down may sensitize these human osteosarcoma cells to doxorubicin and provide a potential therapeutic strategy for osteosarcoma.

[Memory monitoring in mild cognitive impairment].

OBJECTIVE: To explore the profile of changes of memory monitoring in patients with mild cognitive impairment (MCI). METHODS: Rey- auditory verbal learning test (AVLT) and feeling-of-knowing (FOK) test in episodic memory (EM) and semantic memory (SM) were conducted on 30 MCI patients, 17 males and 13 females, aged (66 +/- 9), and 30 age, education level, word fluency test, and digit span-matched healthy persons as healthy control (HC) group. RESULTS: The EM impairment of the MCI group was (13.7 +/- 2.8), significantly higher than that of the HC group [(8.1 +/- 2.0), P < 0.01], but the SM impairment of the MCI group was (5.4 +/- 1.4), not significantly different from that of the HC group [(5.0 +/- 1.4), P > 0.05]. The EM-FOK of the MCI patients with correct judgment and false recognition was (41.8 +/- 13.2)%, significantly higher than that of the HC group [(28.1 +/- 11.6)%, P < 0.01], however, the SM-FOK levels of the MCI patients with different judgment and recognition were all not significantly different from those of the HC group (all P > 0.05). CONCLUSION: The MCI patients overestimate their memory performance on episodic FOK, but their SM monitoring is not impaired. The deficit of memory monitoring in MCI may be the foundation of subjective memory complaints and is useful for diagnosis of MCI. EM and SM monitoring may depend on different neural mechanisms.