Hemorrhagic Outcome of Brainstem Cavernous Malformations following Radiosurgery: Dose-Response Relationship.

INTRODUCTION: This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs). METHODS: A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses. RESULTS: The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042). CONCLUSION: The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Chemical constituents from the leaves and branches of Wikstroemia chamaedaphne with their activation of latent HIV activities.

A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7-9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 µM and compounds 1, 9-11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.

Effect of large volume red blood cell apheresis on cardiovascular functions in healthy donors.

BACKGROUND: Requirements of blood transfusions rise rapidly in China. Improving the efficiency of blood donation could help maintaining sufficient blood supplement. We conducted a pilot research to investigate the reliability and safety of collecting more units of red blood cell by apheresis. METHODS: Thirty-two healthy male volunteers were randomized into two groups: red blood cell apheresis (RA) (n = 16) and whole blood (WB) donation (n = 16). RA group donated individualized RBC volumes by apheresis according to the volunteers' basal total blood volumes and haematocrit levels, WB group donated 400 mL whole blood. All volunteers were scheduled seven visit times in 8 weeks' study period. The cardiovascular functions were assessed by laboratory examinations, echocardiography and cardiopulmonary functional tests. All results were compared between groups at the same visit time and compared between visit 1(before donation) and other visit times within the same group. RESULTS: The average donated RBC volume in RA group and in WB group was 627.25 ± 109.74 mL and 175.28 ± 8.85 mL, respectively(p < 0.05); the RBC, haemoglobin and haematocrit levels changed significantly between times and between groups (p < 0.05). Cardiac biomarker levels such as NT-proBNP, hs-TnT and CK-MB did not change significantly between times or between groups (p > 0.05). The echocardiographic and cardiopulmonary results did not change significantly between times or between groups during the whole study period(p > 0.05). CONCLUSIONS: We provided an efficient and secure method for RBC apheresis. By harvesting more RBC volumes at one single-time, the cardiovascular functions did not change significantly compared with traditional whole blood donation.

Postoperative trigeminal neuropathy outcomes following surgery for tumors involving the trigeminal nerve.

OBJECTIVE: To observe the evolution and outcomes of postoperative trigeminal neuropathy following surgery of tumor involving the trigeminal nerve. METHODS: A prospective observational study was conducted between October 2018 and February 2019 involving 25 patients with tumors confirmed to involve the trigeminal nerve during surgery by senior author. Pre- and postoperative trigeminal nerve function status and clinical data were recorded. RESULTS: This study included 18 cases of meningioma and seven of trigeminal schwannoma. Among the meningioma cases, 55.6% of the patients reported facial sensory dysfunction before surgery, 33.3% presented ocular discomfort, and 5.6% had masticatory muscle atrophy. Postoperatively, all patients experienced facial paresthesia, 94.4% complained of eye dryness, and one (5.56%) exhibited keratitis. Additionally, one patient (5.56%) showed new-onset masticatory weakness. During follow-up, 50.0% of patients reported improvement in facial paresthesia, and one (5.56%) experienced deterioration. Eye dryness resolved in 35.3% of patients, and keratitis remission was observed in one patient. However, one patient (5.56%) developed neurotrophic keratitis. Overall, 55.6% of patients displayed mild masticatory weakness without muscle atrophy. In the cases of schwannoma, 28.6% of patients had facial paresthesia before surgery, 42.9% showed ocular discomfort, and one (14.3%) complained of masticatory dysfunction. Postoperatively, 85.7% of patients reported facial paresthesia and eye dryness, with one patient (16.7%) experiencing keratitis. During follow-up, 66.7% of patients demonstrated improvement in facial paresthesia, 28.6% showed eye dryness remission, and one patient (16.7%) recovered from keratitis. However, one patient (16.7%) developed new-onset neurotrophic keratitis. One patient (16.7%) experienced relief of masticatory dysfunction, but 42.9% reported mild deterioration. Another patient (14.3%) had facial anesthesia that had not improved. CONCLUSION: Postoperative trigeminal neuropathy is a common complication with a high incidence rate and poor recovery outcomes after surgery for tumors involving the trigeminal nerve. When trigeminal nerve damage is unavoidable, it is essential to provide a multidisciplinary and careful follow-up, along with active management strategy, to mitigate the more severe effects of postoperative trigeminal neuropathy.

Phillygenin Attenuated Colon Inflammation and Improved Intestinal Mucosal Barrier in DSS-induced Colitis Mice via TLR4/Src Mediated MAPK and NF-κB Signaling Pathways.

Ulcerative colitis (UC) is a chronic, relapsing, and nonspecific inflammatory bowel disease (IBD). Phillygenin (PHI), a natural bioactive ingredient, isolated from Forsythiae Fructus, exhibits anti-inflammatory, anti-oxidative, and hepatoprotective activities. However, few reports provide direct evidence on the efficacy of PHI in improving colitis mice. The present study elucidated that the symptoms of DSS-induced colitis mice were alleviated after PHI administration, including body weight loss, the disease activity index, colon length shortening, colonic pathological damage, splenomegaly, and hepatomegaly. PHI treatment improved the intestinal mucosal barrier by protecting goblet cells, promoting gene expressions of Clca1, Slc26a3, and Aqp8, increasing tight junction proteins (TJs), and reducing epithelial cell apoptosis. In addition, the levels of oxidative stress (MPO, SOD, and MDA) and inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-10) were reversed by PHI in colitis mice. According to transcriptome and network pharmacology analysis, inflammatory pathway might be an important mechanism for PHI to improve colitis. Western blotting displayed that the PHI inhibited the activation of tyrosine kinase Src mediated by TLR4, and then reduced the phosphorylation of downstream proteins p38, JNK, and NF-κB in colitis mice. In summary, our results suggested that PHI might be an appropriate and effective drug candidate to protect colitis.

TRIM36 enhances lung adenocarcinoma radiosensitivity and inhibits tumorigenesis through promoting RAD51 ubiquitination and antagonizing hsa-miR-376a-5p.

The tripartite motif (TRIM) family proteins exhibit oncogenic or anti-oncogenic roles in various cancers. As a TRIM family member, TRIM36 is expressed in lung adenocarcinoma (LUAD), but its roles remain unexplored. Here, we set to investigate the clinical relevance and the biological actions of TRIM36 in LUAD. mRNA levels of TRIM36 and the Kaplan-Meier survival analysis for patients with LUAD were analyzed from The Cancer Genome Atlas (TCGA) database. Real-time PCR and western blotting were utilized to measure TRIM36 levels both in vivo and in vitro. We demonstrated that TRIM36 levels were significantly decreased in LUAD patients. The low expression of TRIM36 was correlated with a poor prognosis. Overexpression and knock-down studies illustrated that TRIM36 inhibits cell proliferation and promotes apoptosis in LUAD cell lines. LUAD cells were irradiated with 60Co. In addition, TRIM36 enhanced radiosensitivity in LUAD cell lines. Moreover, we found that TRIM36 expression was negatively associated with RAD51. Co-overexpressing RAD51 blocked TRIM36's effects on proliferation and apoptosis. TRIM36 formed a complex with RAD51, promoting its ubiquitination. Inhibiting hsa-miR-376a-5p enhanced apoptosis and the effects were mediated by TRIM36 in response to radiation. In conclusion, our results indicated that TRIM36 is anti-oncogenic in LUAD by promoting RAD1 ubiquitination. Hsa-miR-376a-5p acts upstream of TRIM36. TRIM36 and RAD1 may serve as prognostic indicators for LUAD. The interactions between TRIM36, RAD1 and hsa-miR-376a-5p can be future therapeutic targets to increase radiation sensitivity in LUAD patients.

Association Between Different Versions of the Model for End-Stage Liver Disease Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Pre-procedure liver dysfunction was associated with acute kidney injury after percutaneous coronary intervention (PCI). The aim of this study is to assess and compare the predictive value of different liver function scoring systems for contrast-associated acute kidney injury (CA-AKI) in patients undergoing elective PCI.Methods and Results:A total of 5,569 patients were retrospectively enrolled. The model for end-stage liver disease (MELD) including albumin (MELD-Albumin) score (AUC=0.661) had the strongest predictive value in comparison to the MELD score (AUC=0.627), the MELD excluding the international normalized ratio (MELD-XI) score (AUC=0.560), and the MELD including sodium (MELD-Na) score (AUC=0.652). In the fully adjusted logistic regression model, the MELD-Albumin score and the MELD-Na score were independently associated with CA-AKI regardless of whether they were treated as continuous or categorical variables; however, this was not the case for the MELD score and the MELD-XI score. Furthermore, the addition of the MELD-Albumin score significantly improved the reclassification beyond the fully adjusted logistic regression model. The study further explored the association between different versions of the MELD score and CA-AKI using restricted cubic splines and found a linear relationship between the MELD-Albumin score and the risk of CA-AKI. CONCLUSIONS: The MELD-Albumin score had the highest predictive value for CA-AKI in patients undergoing elective PCI. The addition of the MELD-Albumin score to the existing risk prediction model significantly improved the reclassification for CA-AKI.

Five-year symptomatic hemorrhage risk of untreated brainstem cavernous malformations in a prospective cohort.

Hemorrhage of brainstem cavernous malformation (CM) would cause various symptoms and severe disability. The study aimed to elaborate on the 5-year actuarial cumulative hazard of symptomatic hemorrhage. Patients diagnosed in our institute between 2009 and 2013 were prospectively registered. All clinical data were obtained, follow-up was performed, and risk factors were evaluated. Four hundred sixty-eight patients (217 female, 46.4%) were included in the study with a median follow-up duration of 79.0 months. A total of 137 prospective hemorrhages occurred in 107 patients (22.9%) during 1854.0 patient-years. Multivariate Cox analysis found age ≥ 55 years (hazard ratio (HR) 2.166, p = 0.002), DVA (HR 1.576, p = 0.026), superficial-seated location (HR 1.530, p = 0.047), and hemorrhage on admission (HR 2.419, p = 0.026) as independent risk factors for hemorrhage. The 5-year cumulative hazard of hemorrhage was 30.8% for the overall cohort, 47.8% for 60 patients with age ≥ 55 years, 43.7% for 146 patients with DVA, 37.9% for 272 patients with superficial-seated lesions, and 37.2% for 341 patients with hemorrhage on admission. As a stratified analysis, within subcohort of 341 patients with a hemorrhagic presentation, age ≥ 55 years (HR 3.005, p < 0.001), DVA (HR 1.801, p = 0.010), and superficial-seated location (HR 2.276, p = 0.001) remained independently significant. The 5-year cumulative hazard of hemorrhage was 52.0% for 119 patients with both DVA and hemorrhagic presentation. The 5-year cumulative hemorrhagic risk was 30.8% and was higher in subgroups if harboring risk factors that helped to predict potential hemorrhagic candidates and were useful for treatment decision-making.Clinical Trial Registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR-POC-17011575.

Dietary phillygenin supplementation ameliorates aflatoxin B1-induced oxidative stress, inflammation, and apoptosis in chicken liver.

Aflatoxin B1 (AFB1), a mycotoxin contaminating food and feed, can trigger liver immune toxicity and threaten the poultry industry. Phillygenin (PHI) is a natural lignan derived primarily from Forsythia suspensa with hepatoprotective pharmacological and medicinal properties. This research aimed to investigate the preventive effects of PHI on the toxicity of AFB1 in the liver of chickens. Chickens were administered with AFB1 (2.8 mg/kg) and/or treated with PHI (24 mg/kg) for 33 days. The histopathological changes, serum biochemical indices, oxidative damage, inflammatory mediators, apoptosis, and activation of the NF-κB and Nrf2 signaling pathways were measured. Results revealed that dietary PHI ameliorated liver function indicators, reduced the malondialdehyde and inflammatory mediator production and the apoptotic cell number, and increased the antioxidant enzyme contents and Bcl-2 level. The quantitative realtime PCR and Western blot results revealed that PHI reduced p53, cytochrome c, Bax, caspase-9, and caspase-3 levels, normalized the NF-κB p65 phosphorylation, and upregulated the Nrf2 and its downstream genes expression in chicken liver. These results indicated that PHI has beneficial effects on AFB1-induced liver damage, oxidative damage, inflammatory response, apoptosis, and immunotoxicity by inhibiting NF-κB and activating the Nrf2 signaling pathway in chickens. This study provides new insight into the therapeutic uses of PHI.

Ultrasound analysis of the effect of second delivery on pelvic floor function in Chinese women.

In our study, patients who had a second delivery were categorised into the following 4 groups. Pelvic floor ultrasound data were compared during the 6th week after the second delivery. The incidence of cystoceles was highest in group A and lowest in group D. In addition, groups A and B had a higher rate of rectoceles or perineum descent. Similarly, the areas of the levator hiatus were higher in Groups A and B during Valsalva manoeuvres. The area of the levator hiatus from the resting state to the Valsalva manoeuvre effect had the greatest change in Group A. A comparison of the PR thickening rates among the four groups did not reveal significant differences. All second delivery methods can cause varying degrees of pelvic organ prolapse and decreased pelvic floor function; however, vaginal delivery as the second delivery mode may have a more significant effect in Chinese women.Impact StatementWhat is already known on this subject? Different modes of delivery have significantly different effects on female pelvic floor function. Pregnancy beyond 35 weeks of gestation has an effect on female pelvic floor function, irrespective of the mode of delivery.What do the results of this study add? This study analysed the impact of different delivery modes on Chinese female pelvic floor function. Parous women who underwent different modes of second delivery all demonstrated different degrees of pelvic organ prolapse, as well as pelvic floor function decline.What are the implications of these findings for clinical practice and/or further research? Our study will provide basic research of Chinese female pelvic floor function after a second delivery, which will be of clinical significance around the world, as well as in China. China will keep promoting further delivery as the aging population is increasing. If the developing countries want to promote the second delivery around the women, they have basic research and data to instruct the females.

Insufficient procedural anticoagulation during leadless pacing led to catheter-related thrombosis in a hemodialysis patient.

BACKGROUND: Leadless pacemaker was a promising innovation than traditional transvenous pacemaker, the procedural complications were prone to be bleeding-related. However, very few reports also concerned about the thrombus formation during the procedure. CASE PRESENTATION: A hemodialysis patient with diabetic gangrene of right foot suffered from catheter-related thrombosis during leadless pacing, resulting in failure of recapture the pacemaker. A low activated clotting time (ACT) level of 104 s confirmed the insufficiency of anticoagulation. Finally, the whole delivery catheter had to be removed from the delivery sheath, another new pacemaker system was applied and successfully implanted after adjusting the ACT level to 248 s. CONCLUSION: Catheter-related thrombosis could be a large obstacle for leadless pacemaker implantation. In addition to routine anticoagulation, ACT monitoring might be necessary during the procedure.

Discovering the Mechanisms of Wikstroelide E as a Potential HIV-Latency-Reversing Agent by Transcriptome Profiling.

The discovery of efficient and specific HIV-latency-reversing agents is critical for HIV therapy. Here, we developed wikstroelide E, a daphnane diterpene from the buds of Wikstroemia chamaedaphne, as a potential HIV-latency-reversing agent that is 2500-fold more potent than the drug prostratin. Based on transcriptome analysis, the underlying mechanism was that wikstroelide E regulated the MAPK, PI3K-Akt, JAK-Stat, TNF, and NF-κB signaling pathways. We clearly demonstrated that wikstroelide E reversed latent HIV infection by activating PKC-NF-κB signals, serving as a proxy for verifying the transcriptome data. Strikingly, the Tat protein contributes to the robust activation of latent HIV in wikstroelide-E-treated cells, producing an unexpected latency-reversing effect against latent HIV. This study provides the basis for the potential development of wikstroelide E as an effective HIV-latency-reversing agent.

Natural history of incidentally diagnosed brainstem cavernous malformations in a prospective observational cohort.

There was a lack of natural history of incidental brainstem cavernous malformations (CMs), hemorrhage of which would lead to severe neuropathies. The study aimed to evaluate the prospective hemorrhage rate and neurological outcome of the disease. This prospective cohort included patients with incidental brainstem CMs referred to our institute from 2009 to 2015. The diagnosis was confirmed based on the patients' complain, physical examination, and radiographic evidence. Clinical data were collected, scheduled follow-up was performed, and the independent risk factors were identified by multivariate analysis. This cohort included 48 patients (22 female, 45.8%). The median follow-up duration was 60.7 months, and 13 prospective hemorrhages occurred within 244.0 patient-years yielding an annual hemorrhage rate of 5.3%. The hemorrhage-free survival at 1 and 5 years was 91.6% and 80.6%. Age ≥ 55 years (hazard ratio (HR) = 8.59, p = 0.003), lesion size (per 1-mm increase) (HR = 3.55, p = 0.041), developmental venous anomaly (HR = 10.28, p = 0.017), and perilesional edema (HR = 4.90, p = 0.043) were independent risk factors for hemorrhage. Seven patients (14.6%) received surgical resection, and the other 41 patients remained under observation. Neurological function was improved in 22 patients (45.8%), unchanged in 19 (39.6%), and worsened in 7 (14.6%). Prospective hemorrhage (odds ratio = 14.95, p = 0.037) was the only independent risk factor for worsened outcomes. The natural history of incidental brainstem CMs seemed to be acceptable with improved/unchanged outcomes in most patients (85.4%). These results improved our understanding of the disease, and the future study of a large cohort was required to verify our findings.

Surgical managements and patient outcomes after severe hemorrhagic events from brainstem cavernous malformations.

To evaluate the surgical outcomes and predictors and the impact of surgical timing of patients who suffered a severe hemorrhagic event from brainstem cavernous malformations (CMs). The clinical data of all patients who underwent surgical treatment after a severe bleeding ictus from brainstem CMs between 2011 and 2017 were retrospectively reviewed. The study population consisted of 61 surgical patients (40, 65.6% female). Surgical times of < 3 weeks, ≥ 3-8 weeks, and > 8 weeks since the last bleeding ictus were observed in 23 (37.7%), 24 (39.3%), and 14 (23.0%) patients, respectively. The mean modified Rankin scale (mRS) score evaluated on admission was 4.2. With a mean follow-up of 39.8 months, 39 patients (63.9%) had a favorable outcome (mRS ≤ 2), and the mean mRS score was 2.3. The logistic regression analysis identified age, having disrupted consciousness and/or respiration, and time to surgery from last hemorrhage as significant predictors of long-term outcome. In particular, patients with surgery performed during the acute period (< 3 weeks, P = 0.06) or chronic period (> 8 weeks, P = 0.01) tended to have poor outcomes when compared with those with surgery during the subacute period (≥ 3-8 weeks). Favorable neurological outcomes can be achieved in patients who were surgically treated after a severe hemorrhagic ictus from brainstem CMs, and operation during subacute hemorrhage (≥ 3-8 weeks) could benefit these patients.

The clinicoradiological features and surgical outcomes of primary intracranial fibrosarcoma: a single-institute experience with a systematic review.

Primary intracranial fibrosarcoma (PIF) was a rare tumor with a high relapse rate and dismal survival rate. This study aimed to delineate the clinical characteristics of primary intracranial fibrosarcoma (PIF) and the risk factors for outcomes. We reviewed 15 PIF patients, who underwent surgical treatment at our institution from January 2009 to December 2018. Meanwhile, 36 cases from the prior literature between November 1962 and December 2019 were also retrieved and pooled to identify the risk factors. In our cohort, while cystic component (46.7%), perilesional edema (83.3%), and vascular flow void (66.7%) were commonly observed, no patient was accurately diagnosed. The 2-year relapse-free survival (RFS) and overall survival (OS) were 12.2% and 30.2%, respectively. Based on the pooled data, tumor size (p = 0.006), Ki-67 index (p = 0.004), and radiotherapy dose (p = 0.029) were prognostic factors for RFS in univariate analysis. In the univariate analysis, tumor size (p = 0.002), NGTR (p = 0.049), and high Ki-67 index (p = 0.019) were significant predictors for OS; and further multivariate analysis (n = 18) showed that large tumor size (≥ 5 cm; HR 14.613, p = 0.022) and high Ki-67 index (≥ 30%; HR 5.879, p = 0.020) were the independent risk factors for OS. Due to the rarity and nonspecific clinicoradiological features, the correct diagnosis of PIF before surgery was challenging. The outcomes of PIF were poor, and GTR plus radiotherapy (at least 60 Gy) might benefit to the outcomes and were recommended. Future study with a large cohort was needed to verify our findings.

[Application of fiber photometry in neuroscience research].

In recent years, fiber photometry has been widely used in the field of neuroscience as an important technique for recording the activity of neurons in the specific nuclei of freely moving animal. This review summarized the application of single-channel, multi-channel, and multi-color fiber photometry techniques in the neuroscience research of cognition, behavior, psychology and neurological diseases. In addition, it briefly introduced the applications of fiber photometry combined with functional magnetic resonance imaging technology, and fiber photometry combined with probe technology in the neuroscience research.

Blocking Interleukin-1 Beta Reduces the Evolution of Thoracic Aortic Dissection in a Rodent Model.

OBJECTIVE: Thoracic aortic dissection (TAD) is associated with matrix changes, biochemical changes, and inflammatory markers like interleukin-1 beta (IL-1ß). However, the exact mechanism remains unknown. This study aimed to investigate the role of IL-1ß, matrix metalloproteinase (MMP)-2, MMP-9, smooth muscle cell apoptosis, and elastic fibre fracture in the development of TAD in a rat model. METHODS: The TAD rat model was induced by ß-aminopropionitrile (BAPN). TAD was investigated in 112 male Sprague-Dawley rats, which were equally divided into four groups of 28 rats (Control, BAPN, BAPN + IL-1ß, and BAPN + IL-1ß antibody). Systolic blood pressure, survival, and the development of TAD were measured after six weeks. Expression of IL-1ß, MMP-2, and MMP-9 was measured by Western blot. Apoptosis, aortic elastin concentration, and biomechanical characteristics were measured by the TdT mediated dUTP nick end labelling assay, Victoria blue staining, and in vitro testing. RESULTS: During six weeks, the mortality was 0% (0/28) in the control group, 53.6% (15/28) in the BAPN group (p < .001 compared with the control group), 75.0% (21/28) in the BAPN + IL-1ß group (p = .007 compared with the BAPN group), and 35.7% (10/28) in the BAPN + IL-1ß antibody group (p = .023 compared with BAPN group and p < .001 compared with the BAPN + IL-1ß group). IL-1ß treatment deteriorates BAPN induced mortality and aneurysm expansion, which were attenuated by anti-IL-1ß treatment. In BAPN + IL-1ß group, stress and strain parameters were decreased by 13.5%-53.5% and elastin content was decreased by 14%, and IL-1ß, MMP-2, and MMP-9 were expressed higher by 117%, 108%, and 75% when compared with the rats in the BAPN group. Contrarily, in the BAPN + IL-1ß antibody group, the above changes could be completely (strain, elastin content, and expression of MMP-2) or partly (elasticity modulus, stress, and expression of MMP-9) blocked by anti-IL-1ß treatment. CONCLUSION: IL-1ß plays a critical role in TAD formation by altering the expression of MMP-2 and MMP-9, degrading the aortic wall matrix, causing elastic fibre rupture, and changing the stress or strain of the aortic wall. Anti-IL-1ß reduces the later effects and could be one of the molecular targets for prognosis and drug treatment of TAD in the future.

Pretreatment with atorvastatin ameliorates cobra venom factor-induced acute lung inflammation in mice.

BACKGROUND: The complement system plays a critical role as the pathogenic factor in the models of acute lung injury due to various causes. Cobra venom factor (CVF) is a commonly used complement research tool. The CVF can cause acute inflammation in the lung by producing complement activation components. Atorvastatin (ATR) is a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor approved for control of plasma cholesterol levels. This inhibitor can reduce the acute pulmonary inflammatory response. However, the ability of ATR in treating acute lung inflammation caused by complement activation is still unknown. Therefore, we investigated the effect of ATR on lung inflammation in mice induced by activation of the complement alternative pathway in this study. METHODS: ATR (10 mg/kg/day via oral gavage) was administered for 7 days before tail vein injection of CVF (25 µg/kg). On the seventh day, all mice were sacrificed 1 h after injection. The lung lobe, bronchoalveolar lavage fluid (BALF), and blood samples were collected. The myeloperoxidase (MPO) activity of the lung homogenate, the leukocyte cell count, and the protein content of BALF were measured. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), P-selectin, and Intercellular cell adhesion molecule-1 (ICAM-1) in BALF and serum were determined by enzyme-linked immunosorbent assay. The pathological change of the lung tissue was observed by hematoxylin and eosin staining. The deposition of C5b-9 in the lung tissue was detected by immunohistochemistry. The phosphorylation of NF-κB p65 in the lung tissues was examined by immunohistochemistry and western blotting. RESULTS: The lung inflammation levels were determined by measuring the leukocyte cell numbers and protein content of BALF, the lung MPO activity, and expression and staining of the inflammatory mediators (IL-6 and TNF-α), and adhesion molecules (P-selectin and ICAM-1) for lung lesion. A significant reduction in the lung inflammation levels was observed after 7 days in ATR pre-treated mice with a CVF-induced lung disease. Deposition of C5b-9 was significantly alleviated by ATR pretreatment. Early intervention with ATR significantly reduced the development of acute lung inflammation on the basis of phosphorylation of NF-κB p65 in the lung. CONCLUSION: These findings suggest the identification of ATR treatment for the lung inflammation induced by activating the complement system on the basis of its anti-inflammatory response. Together with the model replicating the complement activating characteristics of acute lung injury, the results may be translatable to the overactivated complement relevant diseases.

Surgical treatment of pontine cavernous malformations via subtemporal transtentorial and intradural anterior transpetrosal approaches.

The aim of this study was to report our surgical experience on resection of the pontine cavernous malformations (CMs) via subtemporal transtentorial approach (STTA) and intradural anterior transpetrosal approach (ATPA). Clinical data were retrospectively reviewed in 61 patients with pontine CMs that were surgically treated by the STTA and the intradural ATPA. The surgical procedures, complications, and outcomes were analyzed. The study consists of 61 patients with a total of 61 pontine CMs. Other than 4 lesions located medially in the pons, all CMs were in the lateral pons with a left or right lateral epicenter (the left/right ratio was 22/35). Totally, 11 patients (18.0%) with lesions located in the upper pons were treated by the STTA, and 50 patients (82.0%) with lesions involving the lower pons were treated by the intradural ATPA. Postoperatively, the complete resection was achieved in 58 patients (95.1%) and incomplete resection in 3 patients (4.9%). Twenty-seven patients (44.3%) suffered from a new or worsened neurological deficit in the immediate postoperative period, and 8 patients (13.1%) encountered a non-neural complication, including rebleeding, cerebrospinal fluid leak, intracranial infection, and pulmonary infection, and 3 patients had contusion of temporal lobe. With a mean follow-up of 54.2 months, the patients' neurological condition had improved in 43 cases (71.6%), not changed in 10 cases (16.7%), and worsened in 7 cases (11.7%), respectively. The Karnofsky Performance Scale (KPS) score evaluated at the last time for per patient was significantly better than their baseline status (t = 6.677, p < 0.001). However, 21 patients (35.0%) suffered from a new or worsened persistent postoperative deficit. The lateral and anterolateral pons can be exposed well by the subtemporal transtentorial and intradural anterior transpetrosal approaches. Lesions of CMs located in the lateral pons, including ventrolateral and dorsolateral pons, could be totally removed by these two lateral approaches with an acceptable surgical morbidity.