Endoscopic ultrasound-guided lauromacrogol injection for treatment of colorectal cavernous hemangioma: Two case reports.

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.

Improving ocular bioavailability of hydrophilic drugs through dynamic covalent complexation.

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.

The analgesic effects of ß-elemene in rats with neuropathic pain by inhibition of spinal astrocytic ERK activation.

Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of ß-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of ß-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1ß, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of ß-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. ß-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. ß-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. ß-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that ß-elemene might be a promising analgesic for the treatment of chronic pain.

Thyroid Disorders and Dementia Risk: A Nationwide Population-Based Case-Control Study.

BACKGROUND AND OBJECTIVES: Dementia has been gaining attention in aging societies and is estimated to affect 50 million adults globally in 2020, and 12% of the US population may develop a thyroid disorder in their lifetime. There have been limited studies investigating the correlation between thyroid disorder and dementia in the Asian population. METHODS: Our large nationwide population-based case-control study used the Taiwanese National Health Insurance Research Database. A total of 7,843 adults with newly diagnosed dementia without a history of dementia or neurodegenerative disease between 2006 and 2013 were identified and included in our study. In addition, 7,843 adults without dementia diagnosis before the index date were age and sex-matched as controls. Diagnosis of hyperthyroidism or hypothyroidism before the diagnosis of dementia or the same index date was identified. Results were obtained from logistic regression models and adjusted for sex, age, history of hypertension, diabetes, coronary artery disease, depression, hyperlipidemia, alcohol dependence syndrome, tinnitus, hearing loss, and radioactive iodine treatment. RESULTS: A total of 15,686 patients were included in the study. Both case and control groups were slightly predominantly female (4,066 [51.8%]). The mean (SD) age for those with dementia was 74.9 (11.3) years and for those without dementia was 74.5 (11.3) years. Among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia (adjusted odds ratio [aOR] 1.81; 95% CI 1.14-2.87; p = 0.011), which was an association not present in patients older than 50 years but younger than 65 years. We found that this association was most significant among patients aged 65 years or older with a history of hypothyroidism who received hypothyroidism medication (aOR 3.17; 95% CI 1.04-9.69; p = 0.043). DISCUSSION: Our large-scale case-control study found that among people aged 65 years or older, those with a history of hypothyroidism were associated with an 81% increased risk of having dementia and among those, there was a more than 3-fold increased dementia risk with thyroid conditions that required thyroid hormone replacement treatment. Future well-controlled prospective longitudinal studies should be conducted to elucidate these potential mechanisms and relationships. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia.

Transoral Robotic Surgery for Early-T Stage Glottic Cancer Involving the Anterior Commissure-News and Update.

BACKGROUND: About 20% of all glottic carcinomas involve the anterior commissure (AC), and AC involvement was deemed to be a risk factor of local recurrence and poor prognosis. Transoral robotic surgery (TORS) has been developed for a panoramic view of the AC and en-bloc resection of the tumor by multidirectional dissection with endo-wristed instruments. With satisfactory preliminary results, we would like to update the data with a bigger cohort and present the news on using TORS for salvage treatment of recurrence from irradiation failure. METHODS: From July 2010 to December 2019, 22 patients with early T1 and 2 stage primary (n = 11) or recurrent (n = 11) glottic cancer with AC involvement received TORS without adjuvant therapy. TORS exposure was found to be better than TLM by conventional laryngoscopy in diagnostic biopsy. Seven of the 22 patients had recurrent cancer from irradiation failure. The perioperative factors that may be associated with survival were retrospectively analyzed, and the 5-year overall survival (OS)/disease-specific survival (DSS)/recurrence-free survival (RFS)/and organ preservation survival (OPS) rate were estimated by the Kaplan-Meier Method. Their voice and swallowing functions were evaluated by questionnaires of Voice Handicap Index-10 (VHI-10) and Functional Outcome Swallowing Scale (FOSS). RESULTS: All 22 TORSs were completed smoothly. After a mean follow-up of 49 ± 35.9 months, the Kaplan-Meier method estimated 5-year OS/DSS/RFS/OPS was 93.8%, 93.8%, 74.6%, and 86.3%, respectively. Our 11 patients with fresh cancer had 100% recurrence-free survival. Although the recurrent rate was higher in patients with history of RT, they could be rescued by further open laryngectomy without compromising the OS and DSS. Only one patient expired. The other 21 patients had satisfactory swallowing function with FOSS of 0.33 ± 0.66. Five patients depended on tracheostomy, but the rest 17 patients had serviceable voice with VHI-10 of 18.41 ± 11.29. CONCLUSIONS: TORS could be used in the primary or salvage management of glottic cancer with AC involvement while TORS was confirmed to have better exposure to TLM. The RFS was good for patients with primary cancer. In patients having irradiation failure, TORS could also be a minimally invasive transoral approach before trying open surgery to preserve the organ.

Predictive value of alarm symptoms in Rome IV irritable bowel syndrome: A multicenter cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria. Alarm symptoms have long been applied in the clinical diagnosis of IBS. However, no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria. AIM: To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria. METHODS: In this multicenter cross-sectional study, we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019. Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records. Eligible patients completed questionnaires, underwent laboratory tests, and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results (if a biopsy was taken). Independent risk factors for organic disease were explored by logistic regression analysis, and the positive predictive value (PPV) and missed diagnosis rate were calculated. RESULTS: The incidence of alarm symptoms in suspected IBS patients was 75.34%. Anemia [odds ratio (OR) = 2.825, 95% confidence interval (CI): 1.273-6.267, P = 0.011], fecal occult blood [OR = 1.940 (95%CI: 1.041-3.613), P = 0.037], unintended weight loss (P = 0.009), female sex [OR = 0.560 (95%CI: 0.330-0.949), P = 0.031] and marital status (P = 0.030) were independently correlated with organic disease. The prevalence of organic disease was 10.41% in suspected IBS patients. The PPV of alarm symptoms for organic disease was highest for anemia (22.92%), fecal occult blood (19.35%) and unintended weight loss (16.48%), and it was 100% when these three factors were combined. The PPV and missed diagnosis rate for diagnosing IBS were 91.67% and 74.77% when all alarm symptoms were combined with Rome IV and 92.09% and 34.10% when only fecal occult blood, unintended weight loss and anemia were combined with Rome IV, respectively. CONCLUSION: Anemia, fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.

Adeno-associated virus vector intraperitoneal injection induces colonic mucosa and submucosa transduction and alters the diversity and composition of the faecal microbiota in rats.

Background: Viral vector technology, especially recombinant adeno-associated virus vector (rAAV) technology, has shown great promise in preclinical research for clinical applications. Several studies have confirmed that rAAV can successfully transduce the enteric nervous system (ENS), and rAAV gene therapy has been approved by the Food and Drug Administration (FDA) for the treatment of the early childhood blindness disease Leber congenital amaurosis and spinal muscular atrophy (SMA). However, until now, it has not been possible to determine the effect of AAV9 on intestinal microbiota. Methods: We examined the efficiency of AAV9-mediated ascending colon, transverse colon and descending colon transduction through intraperitoneal (IP) injection, performed 16S rRNA gene amplicon sequencing and analysed specific faecal microbial signatures following AAV9 IP injection via bioinformatics methods in Sprague-Dawley (SD) rats. Results: Our results showed (1) efficient transduction of the mucosa and submucosa of the ascending, transverse, and descending colon following AAV9 IP injection; (2) a decreased alpha diversity and an altered overall microbial composition following AAV9 IP injection; (3) significant enrichments in a total of 5 phyla, 10 classes, 13 orders, 15 families, 29 genera, and 230 OTUs following AAV9 IP injection; and (4) AAV9 can significantly upregulate the relative abundance of anaerobic microbiota which is one of the seven high-level phenotypes that BugBase could predict. Conclusion: In summary, these data show that IP injection of AAV9 can successfully induce the transduction of the colonic mucosa and submucosa and alter the diversity and composition of the faecal microbiota in rats.

A Pilot Study of the Waterless Empirical Taste Test.

OBJECTIVES: This study was performed to test the clinical applicability of a new taste test-the waterless empirical taste test (WETT). METHODS: Sixty healthy volunteers and 20 patients with oral cancer were enrolled. They all received the conventional solution-based whole-mouth suprathreshold taste test (WMTT), which contained sucrose, citric acid, sodium chloride, and caffeine solutions for tastants, along with the WETT. The WETT used plastic strips to deliver tastants. The strip was embedded with sucrose, citric acid, sodium chloride, caffeine, or monosodium glutamate taste enhancer in 4 different concentrations. Each strip was tested twice. Thirty of the healthy volunteers received the WETT again to measure a retest reliability. Case-control matching by age and gender was used to compare the scores of WMTT and WETT between 13 healthy volunteers and 13 patients with oral cancer. RESULTS: The correlation was not high between the WMTT and WETT (r < 0.7) whether in the healthy volunteers or in patients with oral cancer. In terms of retest reliability of the WETT, the mean total score was 24.9 ± 7.3 for the first test and 25.8 ± 8.4 for the second test. The intraclass correlation coefficient was 0.85 (P < .001). When case-control matching was performed, the WMTT scores were not significantly different between 13 healthy volunteers and 13 patients with oral cancer (P = .266), but the WETT scores were significantly lower in patients with oral cancer (P = .017). CONCLUSION: This study showed that the results of the WETT were not highly correlated with those of the WMTT. However, its retest reliability was high, and its results were significantly different between the healthy volunteers and the patients with oral cancer.

Predictors of nasal bacterial culture rates in patients with chronic rhinosinusitis.

All nontechnical factors were analyzed to predict nasal bacterial culture results in patients with chronic rhinosinusitis (CRS). Four hundred and ninety-six CRS patients, who underwent functional endoscopic sinus surgery (FESS), were enrolled. Prior to FESS, the severity of each patient's CRS was evaluated using a questionnaire, endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and CT scan. Nasal bacterial cultures were collected from both middle meati using a cotton-tipped stick. Our results showed that the symptom severity complained of by patients and their loss of smell function did not influence the bacterial culture rate. We discovered that the bacterial culture rate was significantly higher in nostrils with nasal polyps than those without polyps, along with nostrils experiencing thick, purulent discharge as opposed to those without discharge. Additionally, this result also occurred in nostrils with a saccharin transit time of more than 30 min than it did in those with a saccharin transit time of less than or equal to 30 min. Both the total endoscopic score and anterior group CT score were significantly higher in nostrils with positive culture than those with negative culture, while the second minimal cross-sectional area (MCA2) of the nasal cavity was significantly lower in nostrils with positive culture than those with negative culture. Multiple logistic regression analysis showed that both nasal polyps and MCA2 were the predictors for positive nasal bacterial culture results. It was concluded that nasal polyps and MCA2 were the predictors for positive nasal bacterial culture results in CRS patients.

miR-222 targets ACOX1, promotes triglyceride accumulation in hepatocytes.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. However, the exact pathogenesis of NAFLD remains to be elucidated. Despite the association with tumors and cardiovascular diseases, the role of miR-222 in NAFLD remains unclear. The present study was to investigate the role of miR-222 in NAFLD. METHODS: Wild-type C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD. Normal human liver cell line (L02) was cultured with free fatty acid (FFA)-containing medium to stimulate cell steatosis. The mRNA levels of miR-222 and acyl Coenzyme A xidase 1 (ACOX1) were detected by quantitative-PCR (Q-PCR). The prediction of ACOX1 as the target gene for miR-222 was conducted via TargetScan. The overexpression or inhibition of miR-222 was mediated by miR-222 mimics or antagomir, and intracellular triglyceride levels were measured using a triglyceride kit. Luciferase reporter assays verified ACOX1 as the target gene for miR-222. RESULTS: miR-222 was significantly elevated in both the in vivo and in vitro NAFLD models. Overexpression of miR-222 significantly increased triglyceride content in the L02 cells, while inhibition of miR-222 expression restricted the accumulation of triglyceride. Overexpression of miR-222 significantly inhibited ACOX1 expression. Transient transfection assays verified that ACOX1 3'-UTR luciferase reporter activity could be inhibited by miR-222 overexpression. CONCLUSIONS: The present study suggested that miR-222 promotes the accumulation of triglycerides by inhibiting ACOX1.

Impact of antibiotics on smell dysfunction.

OBJECTIVE: Viral or bacterial respiratory infections can cause long-lasting olfactory dysfunction. Antibiotic therapy is indicated in severe cases; however, it is unclear whether antibiotic use produces a positive, negative, or null effect on olfactory function. This retrospective study sought to determine whether antibiotic use has an influence on odor identification and detection threshold test scores of patients with smell dysfunction secondary to upper respiratory infections (URIs), lower respiratory infections (LRIs), or rhinosinusitis. METHODS: Data from a total of 288 patients presenting to the University of Pennsylvania Smell and Taste Center were evaluated. RESULTS: Patients with a URI etiology who had taken bactericidal antibiotics had lower detection thresholds than did patients who had not taken antibiotics (P < 0.023; analysis of covariance with age and time since infection onset as covariates). Moreover, thresholds were lower for bactericidal antibiotic users than for bacteriostatic antibiotic users with either URI (P = 0.023) or rhinosinusitis (P = 0.028) etiologies. No meaningful influences of antibiotics on the odor identification test scores were evident. CONCLUSIONS: These findings, which need to be confirmed in prospective double-blind studies, suggest that bactericidal antibiotic therapy may be beneficial in mitigating, at least to some degree, chronic decrements in smell sensitivity due to URIs and rhinosinusitis.

Risk factors for recurrent pneumonia in post-irradiated patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common cancer in eastern Asia. Chemoradiotherapy is the main treatment modality for NPC. Dysphagia and aspiration is not uncommon in post-irradiated NPC patients. The purpose of this study was to investigate the risk factors for recurrent pneumonia and the prognosis. METHODS: A retrospective chart review was conducted from January 2004 to December 2014. NPC patients who had been hospitalized for pneumonia in the study hospital were enrolled. The diagnosis of pneumonia was based on radiological evidence of chest inflammation and clinical symptoms. Patients' characteristics including demographic data, the hospital course, and the outcome of pneumonia were collected and analyzed. RESULTS: A total of 113 NPC patients were enrolled in this study. Among them, 96 NPC patients had pneumonia after radiotherapy: 43 had pneumonia twice, and 18 had multiple episodes of pneumonia. Forty-nine patients had tube feeding. The 30-day mortality rate was 51%. The mortality rate was significantly associated with metastatic nasopharyngeal carcinoma (r = 0.328, p < 0.001). Older age, smoking, body weight loss, and lower cranial nerve (vagus or hypoglossal nerve palsy) were significant predictors of multiple episodes of pneumonia (r2 = 0.687, p = 0.033, 0.034, 0.036, and 0.027, respectively). CONCLUSION: We concluded that old age, smoking, body weight loss, and lower cranial nerve palsies are predisposing factors for multiple episodes of pneumonia in post-irradiated NPC patients. Metastatic cancer status usually leads to a lethal outcome. Early interventions to manage dysphagia in high-risk patients are necessary.

Olfactory change after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy is the mainstay of treatment for nasopharyngeal cancer (NPC), but many side effects were reported in NPC patients receiving radiotherapy. This study was conducted to evaluate the long-term effects of intensity-modulated radiotherapy (IMRT) on olfactory function. METHODS: The olfactory function of 41 NPC patients was assessed by a traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). The patients also filled out a Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22) questionnaire and received imaging examinations of the sinuses before IMRT and 1 year after IMRT. The sinus imaging was scored according to the Lund-Mackay system. RESULTS: The mean UPSIT-TC scores were 30.6 before IMRT and 28.0 after IMRT and the decrease in UPSIT-TC scores was significant (p = 0.001). The mean TWSNOT-22 scores were 32.1 before IMRT and 28.8 after IMRT. The change in TWSNOT-22 scores was not significant, but the scores for item 5 "loss of smell or taste" significantly increased after IMRT (p = 0.035). The mean total computed tomography (CT) scores were 1.7 before IMRT and 3.2 after IMRT, and the mean ethmoid CT scores were 0.5 before IMRT and 1.2 after IMRT. The increase in total CT and ethmoid CT scores was both significant (p = 0.004 and 0.002). The decrease in UPSIT-TC scores was moderately negatively correlated with the increase in total CT and ethmoid CT scores (r = -0.348 and -0.423). CONCLUSION: Our results showed that the olfactory function of NPC patients was mildly impaired after IMRT, which can cause rhinosinusitis.

[Study of collagen mimetic peptide's triple-helix structure and its thermostability by circular dichroism].

In the present study, the authors explore the triple-helix conformation and thermal stability of collagen mimetic peptides (CMPs) as a function of peptide sequence and/or chain length by circular dichroism(CD). Five CMPs were designed and synthetized varying the number of POG triplets or incorporating an integrin alpha2beta1 binding motif Gly-Phe-Hyp-Gly-Glu-Arg (GFOGER). CD spectroscopy from 260 to 190 nm was recorded to confirm the existence of triple-helix conformation at room temperature, while thermal melting and thermal annealing of triple-helix (thermal unfolding and refolding of triple-helix, respectively) was characterized by monitoring ellipticity at 225 nm as a function of temperature. The results demonstrated that all the CMPs adopted triple-helix conformation, and the thermal stability of the CMPs was enhanced with increasing the number of POG triplets. In contrast to natural collagen, the thermal denaturation processes of CMPs were reversible, i. e. the triple-helix unfolded upon heating while refolded upon cooling. Meanwhile, the phenomenon of "hysteresis" was observed by comparing melting and thermal curves. These findings add new insights to the mechanisms of collagen and CMPs assembly, as well as provide an alternative approach to the fabrication of artificial collagen-likes biomaterials.

LPS-induced proNGF synthesis and release in the N9 and BV2 microglial cells: a new pathway underling microglial toxicity in neuroinflammation.

PURPOSE: While aberrant activation of microglial cells was evidently involved in neuroinflammation and neurotoxicity in the neurodegenerative diseases such as Alzheimer's and Parkinson's disease, objective of study was to address if activated microglias deliver their effect by releasing pro-neurotrophins. MATERIALS AND METHODS: By in vitro culture of N9 and BV2 cell lines and lipopolysaccharide (LPS) stimulation model, generation and release of proNGF, proBDNF and MMP-9 was studied in the activated microglial cells by immunocytochemistry, western blotting and bioassay methods. RESULTS: Activation of microglial cells was observed with obvious increasing iba1-immunoreactivity following LPS stimulation in cell culture. Synthesis and up-regulation of proNGF protein significantly occurred in N9 and BV2 cells 12h-48h after LPS exposure, whereas no significant changes of proBDNF and MMP9 were observed in these microglial cell lines with LPS insult. More interestingly, extracellular release or secretion of proNGF molecule was also detected in culture medium of N9 cells after LPS stimulation. Finally, bioassay using MTT, Hoechst/PI and TUNEL staining in SH-SY5Y cells further confirmed that proNGF treatment could result in apoptotic cell death but it did not significantly influence cell viability of SH-SY5Y cells. CONCLUSIONS: This in vitro study revealed LPS-stimulated proNGF synthesis and release in activated N9/BV2 microglial cell lines, also suggesting that proNGF may appeal a new pathway or possible mechanism underlying microglial toxicity in the neuroinflammation and a potential target for therapeutic manipulation of the neurodegenerative diseases.

Presence of proNGF-sortilin signaling complex in nigral dopamine neurons and its variation in relation to aging, lactacystin and 6-OHDA insults.

Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a crucial factor in neurodegeneration, but it remains unclear if it may function in nigral neurons under aging and disease. The purpose of this study is to examine and quantify proNGF and sortilin expression in the substantia nigra and dynamic changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease using immunofluorescence, electronic microscopy, western blot and FLIVO staining methods. The expression of proNGF and sortilin was abundantly and selectively identified in tyrosine hydroxylase (TH)-containing dopamine neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons were densely distributed in the ventral tier, while they were less distributed in the dorsal tier, where calbindin-D28K-containing neurons were numerously located. A correlated decrease of proNGF, sortilin and TH was also detected during animal aging process. While increase of proNGF, sortilin and cleaved (active) caspase-3 expression was found in the lactacystin model, dynamic proNGF and sortilin changes along with dopamine neuronal loss were demonstrated in the substantia nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and its response to aging, lactacystin and 6-OHDA insults, suggesting that it might contribute to neuronal apoptosis or neurodegeneration during pathogenesis and disease progression of Parkinson's disease; the underlying mechanism and key signaling pathways involved warrant further investigation.

[Influence of different tranexamic acid administration methods during and after cardiac surgery on coagulation function and postoperative blood loss].

OBJECTIVE: To evaluate the influence of different tranexamic acid administration methods during and after cardiac surgery with cardiopulmonary bypass(CPB) on coagulation function and postoperative bleeding. METHODS: Patients undergoing elective cardiac surgery with use of CPB (n=60) were randomized in a double-blind fashion to one of two treatment groups:group A(n=30) , administered with tranexamic acid 10 mg/kg (intravenous injection slowly before skin incision) , followed by infusion of normal saline until postoperative 12 hours;and group B(n=30) , administered with tranexamic acid 10 mg/kg(intravenous injection slowly before skin incision) , followed by infusion of tranexamic acid 1 mg/(kg·h) until postoperative 12 hours. Hemoglobin, platelet count, and coagulation function were assessed before anesthesia induction, after surgery, 8am next day and 24 hours after surgery. Bleeding, allogeneic blood transfusion, and fluid infusion during the postoperative 24 hours were recorded. RESULT: No differences were found between groups in terms of coagulant function, postoperative bleeding, allogeneic blood transfusion, and fluid infusion(P>0.05) . CONCLUSION: Compared with intraoperative administration alone, prolonged treatment with tranexamic acid after cardiac surgery shows no advantage because it can not further improve coagulant function, reduce bleeding, or reduce allogeneic blood transfusion.

Iron deposition in the precentral grey matter in patients with multiple sclerosis: a quantitative study using susceptibility-weighted imaging.

PURPOSE: Several studies suggest that iron deposition may play a role in multiple sclerosis (MS) pathology. Three-dimensional (3D) enhanced T2*-weighted angiography (ESWAN) at 3T was used to quantify iron deposition in the precentral grey matter in MS and its relationship with disease duration, atrophy and Expanded Disability Status Scale (EDSS) scores. METHODS: We recruited 33 patients with diagnosis of clinically definite MS and 31 age- and sex-matched healthy controls who underwent conventional brain MRI, 3D-ESWAN and 3D T1sequences. We obtained the mean phase values (MPVs) of the precentral grey matter on ESWAN-filtered phase images and volume of the precentral gyrus on 3D T1 images. We investigated the correlation between precentral grey matter MPVs, precentral gyrus volume, disease duration and EDSS scores of MS patients and healthy controls. RESULTS: The precentral grey matter MPVs in MS patients and controls were 1870.83 ± 56.61 and 1899.22 ± 51.73 respectively and had significant difference in the MS group vs. the control group (t=-2.09, P=0.04). There was significant negative correlation between precentral grey matter MPVs and disease duration (r=-0.365, P=0.03). No correlation was found between MPVs and EDSS scores. Mean precentral gyrus volume in MS patients was 4368.55 ± 867.78 whereas in controls was 5701.00 ± 1184.03 with significant difference between volume of the precentral gyrus in MS patients compared to healthy controls (t=-5.167, P<0.001). There was a positive correlation between MPVs and precentral gyrus volume (r=0.291, P=0.020). CONCLUSIONS: Our study demonstrated that quantitative assessment of abnormal iron deposition in the precentral grey matter in MS patients can be measured using 3D-ESWAN.

[Analgesic effect of calpain inhibitor ALLN on the zymosan-induced paw inflammatory pain and its effect on the expression of cyclooxygenase-2 in the spinal dorsal horn].

OBJECTIVE: To examine the analgesic effect of calpain inhibitor ALLN on the zymosan-induced paw inflammatory pain and its effect on the expression of cyclooxygenase-2 (COX-2) in the spinal dorsal horn. METHODS: Forty-eight Sprague-Dawley rats were equally divided into three groups: control group, sham-operated group, and zymosan group. According to Meller's method, zymosan (1.25 mg) was injected intraplantarly to induce paw inflammation in zymosan group; an equal volume of PBS was administered in the sham-operated group. Mechanical withdrawal threshold (MWT) and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine calpain activity in the spinal dorsal horn with Western blot analysis. Another sixty-four Sprague-Dawley rats were divided into three groups: sham-operated group, zymosan-induced paw inflammation with intraperitoneal dimethyl sulphoxide (DMSO) treatment group, and zymosan-induced paw inflammation with intraperitoneal calpain inhibitor ALLN treatment group. MWT and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine the COX-2 expression in the spinal dorsal horn with Western blot analysis. RESULTS: MWT significantly decreased in the rats with zymosan-induced paw inflammation, while the maximum thickness of paw significantly increased, compared with control and sham-operated rats (P < 0.05). Calpain in the ipsilateral spinal dorsal horn was dramatically activated after zymosan injection (P < 0.01). Intraperitoneal ALLN injection significantly increased zymosan-induced MWT and decreased paw edema at the same time points after zymosan injection compared with DMSO treatment group (P < 0.05). Meanwhile, calpain inhibitor ALLN treatment significantly decreased the COX-2 expression in the spinal dorsal horn compared with DMSO treatment (P < 0.01). CONCLUSION: Administration of calpain inhibitor ALLN is effective to attenuate zymosan-induced paw inflammatory pain. Calpain activation may be one aspect of the signaling cascade that increases the COX-2 expression in the spinal cord and contributes to mechanical hyperalgesia after peripheral inflammatory injury.