Endovascular therapy beyond 24 hours for anterior circulation large vessel occlusion or stenosis in acute ischemic stroke: a retrospective study.

Background: To assess the clinical and safety outcomes of endovascular treatment (EVT) administered more than 24 h after the onset of symptoms in patients with acute ischemic stroke resulting from anterior circulation large-vessel occlusion or stenosis (AIS-ACLVO/S). Methods: We enrolled consecutive AIS-ACLVO/S patients who received EVT in our hospital between January 2019 and February 2022 and divided them into two groups based on the time from AIS onset to EVT: EVT < 24 h group and EVT >24 h group. The successful reperfusion (modified thrombolysis in cerebral infarction, [mTICI] ≥2b), 90-day modified Rankin Scale score (mRS), intracranial hemorrhage (ICH), and symptomatic ICH (sICH), as well as mortality, were analyzed in the two groups of patients. Results: A total of 239 patients were included in the study, with 214 patients in the EVT < 24 h group (67.8 ± 0.8 years, 126 males) and 25 patients in the EVT > 24 h group (62.80 ± 2.0 years, 22 males). Both groups were similar in terms of hypertension, diabetes history, responsible vessels, and Alberta stroke program early computed tomography scores (p > 0.05). However, the EVT < 24 h group had significantly higher age, history of atrial fibrillation, proportion of patients receiving intravenous thrombolysis, and NIHSS scores before EVT than the EVT > 24 h group. AIS etiology differed between the groups, with more cases of large artery atherosclerosis in the EVT > 24-h group and more cases of cardioembolism in the EVT < 24-h group. Successful reperfusion (mTICI ≥2b), ICH, and sICH were similar between the groups. The 90-day functional independence rate (mRS ≤ 2) was significantly higher in the EVT > 24-h than in the EVT < 24-h group (80% vs. 39.7%, p < 0.001), while the 90-day mortality rate was lower in the EVT > 24-h group (0% vs. 24.8%, p < 0.001). Conclusion: In our study, we found that EVT beyond 24 h of symptom onset in patients selected with multimodal MR screening, was associated with high functional independence rates and low mortality. Larger or randomized studies are needed to confirm these findings.

A systematic review and meta-analysis of the diagnostic accuracy of metagenomic next-generation sequencing for diagnosing tuberculous meningitis.

Objective: The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to comprehensively evaluate its diagnostic accuracy for the early diagnosis of TBM. Methods: English (PubMed, Medline, Web of Science, Cochrane Library, and Embase) and Chinese (CNKI, Wanfang, and CBM) databases were searched for relevant studies assessing the diagnostic accuracy of mNGS for TBM. Review Manager was used to evaluate the quality of the included studies, and Stata was used to perform the statistical analysis. Results: Of 495 relevant articles retrieved, eight studies involving 693 participants (348 with and 345 without TBM) met the inclusion criteria and were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver-operating characteristic curve of mNGS for diagnosing TBM were 62% (95% confidence interval [CI]: 0.46-0.76), 99% (95% CI: 0.94-1.00), 139.08 (95% CI: 8.54-2266), 0.38 (95% CI: 0.25-0.58), 364.89 (95% CI: 18.39-7239), and 0.97 (95% CI: 0.95-0.98), respectively. Conclusions: mNGS showed good specificity but moderate sensitivity; therefore, a more sensitive test should be developed to assist in the diagnosis of TBM.

Recent advances in microbiological and molecular biological detection techniques of tuberculous meningitis.

Tuberculous meningitis (TBM) is the most common type of central nervous system tuberculosis (TB) and has the highest mortality and disability rate. Early diagnosis is key to improving the prognosis and survival rate of patients. However, laboratory diagnosis of TBM is often difficult due to its paucibacillary nature and sub optimal sensitivity of conventional microbiology and molecular tools which often fails to detect the pathogen. The gold standard for TBM diagnosis is the presence of MTB in the CSF. The recognised methods for the identification of MTB are acid-fast bacilli (AFB) detected under CSF smear microscopy, MTB cultured in CSF, and MTB detected by polymerase chain reaction (PCR). Currently, many studies consider that all diagnostic techniques for TBM are not perfect, and no single technique is considered simple, fast, cheap, and efficient. A definite diagnosis of TBM is still difficult in current clinical practice. In this review, we summarise the current state of microbiological and molecular biological diagnostics for TBM, the latest advances in research, and discuss the advantages of these techniques, as well as the issues and challenges faced in terms of diagnostic effectiveness, laboratory infrastructure, testing costs, and clinical expertise, for clinicians to select appropriate testing methods.

Incidence and Risk Factors of Cranial Nerve Palsy in Patients with Tuberculous Meningitis: A Retrospective Evaluation.

Objective: Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics. Methods: A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM. Results: A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy. Conclusion: The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.

Exploration of the Risk Factors of Anemia in Patients with Tuberculous Meningitis in South China.

Objective: Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5-6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person's susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients. Methods: We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM. Results: Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia. Conclusion: Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.

Clear cell renal cell carcinoma with cystic component similar to multilocular cystic renal neoplasm of low malignant potential: a rare pattern of cyst-dependent progression from multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: For clear cell renal cell carcinoma (ccRCC) with cystic component similar to multilocular cystic renal neoplasm of low malignant potential (MCRN-LMP) and solid low-grade component simultaneously, we propose the designation "ccRCC with cystic component similar to MCRN-LMP" and to study the relationship between MCRN-LMP and it. METHODS: Twelve cases of MCRN-LMP and 33 cases of ccRCC with cystic component similar to MCRN-LMP were collected from 3,265 consecutive RCCs to compare them in clinicopathological features, immunohistochemical findings (PAX8, CA-IX, CK7, Vimentin, CD10, P504s, TFE3, 34ßE12) and prognosis. RESULTS: There was no significant difference in age, sex ratio, tumor size, treatment, grade and stage between them (P > 0.05). All ccRCCs with cystic component similar to MCRN-LMP coexisted with MCRN-LMP and solid low-grade ccRCCs, and MCRN-LMP component ranged from 20 to 90% (median, 59%). The positive ratio of CK7 and 34ßE12 in MCRN-LMPs and ccRCCs' cystic parts was significantly higher than that in ccRCCs' solid parts, but the positive ratio of CD10 in MCRN-LMPs and ccRCCs' cystic parts was significantly lower than that in ccRCCs' solid parts (P < 0.05). There was no significant difference of all immunohistochemistry profiles between MCRN-LMPs and ccRCCs' cystic parts (P > 0.05). No patient developed recurrence or metastasis. CONCLUSIONS: MCRN-LMP and ccRCC with cystic component similar to MCRN-LMP have similarity and homology in clinicopathological features, immunohistochemical findings and prognosis, and form a low-grade spectrum with indolent or low malignant potential behavior. The ccRCC with cystic component similar to MCRN-LMP may be a rare pattern of cyst-dependent progression from MCRN-LMP.

Diagnostic Accuracy of Interferon-Gamma Release Assays for Tuberculous Meningitis: A Systematic Review and Meta-Analysis.

Background: In this study, we evaluated and compared the accuracy of blood and cerebrospinal fluid (CSF) interferon release tests [interferon-gamma release assays (IGRAs)] in the diagnosis of tuberculous meningitis (TBM) by a meta-analysis of the relevant literature. Methods: We searched for studies published before 2021 in Medline, Embase, the Cochrane database, and Chinese databases. All studies used the QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB method. Blood and/or CSF tests that met the guidelines for the quality assessment of studies with diagnostic accuracy were included. We used the revised diagnostic accuracy study quality assessment to assess the quality of the included studies. Begg's funnel plots were used to assess publication bias in the meta-analysis of the diagnostic studies, and statistical analyses were performed by using Stata (Version 12) software. Results: A total of 12 blood and/or CSF IGRA studies were included in this meta-analysis, with 376 patients and 493 controls. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (SROC) of the blood IGRAs in the pooled data from 12 studies were 74% (95% CI: 0.65-0.82), 78% (95% CI: 0.68-0.86), 3.38 (95% CI 2.26-5.06), 0.33 (95% CI: 0.23-0.46), 10.25 (95% CI: 5.46-19.25), and 0.83 (95% CI: 0.79-0.86), respectively. For CSF IGRAs, these values for the pooled data from the 10 studies included were 79% (95% CI: 0.71-0.85), 95% (95% CI: 0.88-0.98), 16.30 (95% CI 6.5-40.83), 0.22 (95% CI: 0.16-0.31), 57.93 (95% CI: 22.56-148.78), and 0.91 (95% CI: 0.88-0.93), respectively. Conclusion: CSF IGRAs exhibited a better diagnostic accuracy than blood IGRAs in diagnosing TBM.

A New Scoring System to Differentially Diagnose and Distinguish Tuberculous Meningitis and Bacterial Meningitis in South China.

Background: Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis, and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China. Methods: A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule. Results: Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively. Conclusion: The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources.

Bipolar disorder and the risk for stroke incidence and mortality: a meta-analysis.

OBJECTIVE: Bipolar disorder (BD) may be associated with an increased risk of stroke, but to date, the results of the studies are still controversial. This study aimed to assess the association of BD with stroke incidence and mortality by a meta-analysis. METHOD: PubMed, EMBASE, the Cochrane library databases, and Web of Science databases were searched from inception to July 2020. We regarded stroke as a composite endpoint. The pooled hazard ratio (HRs) of 95% confidence interval (Cls) was calculated. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity of the pooled estimation. RESULTS: A total of 7 studies involving a total of 13,305,007 participants were included in this meta-analysis. Pooled analysis showed participants with BD experienced a significantly increased risk of both stroke incidence (combined HR, 1.43; 95% CI, 1.24-1.66; p = 0.000) and stroke mortality (combined HR, 1.54; 95% CI, 1.09-2.18; p = 0.013) compared to participants without BD. In addition, the pooled estimate of multivariate HRs of stroke incidence and mortality were 1.35 (95% CI: 1.26-1.45); 2.30 ( 95% CI: 1.37-3.85) among men and 1.43 (95% CI:1.27-1.60); 2.08 (95% CI:1.60-2.71) among women respectively. CONCLUSIONS: This meta-analysis suggests that BD may modestly increase the risk of both stroke incidence and mortality. Extensive clinical observational studies should be conducted in the future to explore whether BD is a potentially modifiable risk factor for stroke.

Association between kidney stones and risk of developing stroke: a meta-analysis.

BACKGROUND: Many studies have described the relationship between kidney stones and stroke, but the results are controversial, so we conducted this meta-analysis to estimate the relationship between kidney stones and the risk of developing stroke. METHODS: Studies were marked with a comprehensive search of PubMed, EMBASE, Google, and ISI Web of Science databases through 25 March 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and a random-effects model or fix-effects model was used to compute the pooled combined risk estimate. Heterogeneity was reported as I2. We performed subgroup and sensitivity analysis to assess potential sources of heterogeneity. RESULTS: Eight studies of seven articles involving 3,526,808 participants were included in the meta-analysis. Overall, kidney stones were associated with a moderate risk of stroke incidence (HR, 1.24; 95% CI, 1.11-1.40; I2=79.6%; p=0.000). We conducted a sensitivity analysis by removing the studies that had a high risk of bias. Heterogeneity subsequently decreased significantly, while an increased risk of stroke in patient with kidney stones was again demonstrated (HR, 1.16; 95% CI, 1.11-1.23; I2=28.7%; p=0.000). Stratifying analysis showed that the results were more pronounced for ischemic stroke (HR, 1.14; 95% CI, 1.08-1.22; I2=15.6%; p=0.00) and the follow-up duration ≥10 years (HR, 1.18; 95% CI, 1.10-1.27; I2=31.6%; p=0.003). CONCLUSIONS: Our meta-analysis suggests that patients with kidney stones may have a modestly increased risk of developing stroke, especially in ischemic stroke. More large-scaled and clinical trials should be done to identify the relative impact of kidney stones on stroke outcomes in the future.

[Long-term outcomes of 125I brachytherapy combined with maximal androgen blockade for metastatic prostate cancer].

OBJECTIVE: To investigate the long-term clinical value of prostate 125I brachytherapy (BT) combined with maximal androgen blockade (MAB) in the treatment of metastatic prostate cancer (mPCa). METHODS: We retrospectively analyzed the clinical data on 173 cases of mPCa treated by MAB (n = 126) or BT+MAB (n = 47) from December 2011 to December 2016 and followed up for 6－76 (44.17 ± 19.73) months. We compared the PSA level, prostate volume, IPSS, progression-free survival, and the rates of 3- and 5-year overall survival between the two groups. RESULTS: After treatment, the minimum PSA level was significantly lower in the BT+MAB than in the MAB group ï¼»3.77 ± 4.14ï¼½ vs ï¼»5.96 ± 7.01ï¼½ ng/ml, P = 0.046) and the time to reach the minimum level was shorter in the former than in the latter (ï¼»5.19 ± 2.83ï¼½ vs ï¼»6.52 ± 3.34ï¼½ mo, P = 0.016). The prostate volume was markedly reduced in both of the groups at 1, 3 and 5 years after treatment as compared with the baseline, even more significantly in the BT+MAB than in the MAB group (P < 0.01), though with no statistically significant difference between the two groups before treatment (P = 0.307). The IPSS was remarkably decreased in both of the groups at 1 and 3 years (P < 0.01) but showed no significant difference at 5 years after treatment as compared with the baseline (P > 0.05) or between the two groups before and after treatment (P > 0.05). The progression-free survival was obviously longer in the BT+MAB than in the MAB group (ï¼»37.29 ± 15.73ï¼½ vs ï¼»29.41 ± 14.37ï¼½ mo, P = 0.011), and the rates of 3- and 5-year overall survival were higher in the former than in the latter (74.60% and 60.70% vs 62.60% and 51.50%, P = 0.227 and P = 0.356). Kaplan-Meier survival curves showed no statistically significant difference in the overall survival between the two groups (P = 0.105). CONCLUSIONS: Both MAB and BT+MAB are effective therapies for mPCa, but the latter can achieve a longer progression-free survival.

Effect of glycated hemoglobin index and mean arterial pressure on acute ischemic stroke prognosis after intravenous thrombolysis with recombinant tissue plasminogen activator.

To determine whether glycated hemoglobin and mean arterial pressure (MAP) during thrombolysis are prognostic factors of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS).A total of 125 AIS patients, who received rt-PA intravenous thrombolysis in our hospital, were included into the present study, and divided into good prognosis group and poor prognosis group. Univariate and multivariate logistic regression analyses were used to determine the prognostic factors of AIS treated by rt-PA thrombolysis, Spearman correlation analysis was used to analyze the correlation of the accumulated cigarette consumption in the smoking subgroup and glycated hemoglobin in the diabetic subgroup with the prognosis after intravenous thrombolysis and the symptomatic intracranial hemorrhage (sICH).Univariate analysis revealed that the interval from onset to thrombolysis, baseline National Institutes of Health Stroke Scale (NIHSS) score, MAP during thrombolysis and DRAGON score were prognostic factors. Multivariate logistic regression analysis revealed that baseline NIHSS score and MAP during thrombolysis were independent prognostic factors for rt-PA thrombolysis. Furthermore, the glycated hemoglobin index was positively correlated with the incidence of sICH.The NIHSS score before thrombolysis and MAP during thrombolysis were independent factors for the prognosis of AIS treated by thrombolysis. The higher the glycated hemoglobin index of diabetic patients, the more likely they are to develop sICH, the glycated hemoglobin index was negatively correlated with the prognosis after intravenous thrombolysis. The accumulated cigarette consumption was negatively correlated with the prognosis after intravenous thrombolysis.

Relationship of atopic dermatitis with stroke and myocardial infarction: A meta-analysis.

BACKGROUND: Lots of previous reports have suggested a potential association of atopic dermatitis (AD) with stroke and myocardial infarction (MI). However, the result is still controversial, Consequently, we conducted this meta-analysis to estimate the relationship of AD with Stroke and MI. METHODS: PubMed, Embase, and Web of Science databases were searched from inception to June 2018. Stroke and MI were considered as a composite endpoint. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analysis were performed to assess the potential sources of heterogeneity of the pooled estimation. RESULTS: A total of 12 articles with 15 studies involving 3,701,199 participants were included in this meta-analysis. Of these, 14 studies on stroke and 12 on MI. Pooled analysis showed participants with AD experienced a significant increased risk of stroke (combined HR, 1.15; 95% CI, 1.08-1.22; P = .000) and MI (combined HR, 1.13; 95% CI, 1.02-1.24; P = .014), compared with participants without AD. The risk of stroke and MI was significant both in male subjects (stroke: HR: 1.33, 95% CI: 1.14-1.56; MI: HR: 2.01, 95% CI: 1.31-3.08), but not in female subjects (HR: 1.02, 95% CI: 0.77-1.35; MI: HR: 0.98, 95% CI: 0.72-1.32). The results were more pronounced for ischemic stroke (HR: 1.16, 95% CI: 1.13-1.19) in the stratified with stroke type. Stratifying by AD type, the risk of stroke was significant in severe AD (HR: 1.29, 95% CI: 1.08-1.54) and moderate AD (HR: 1.11, 95% CI: 1.01-1.22) for MI. CONCLUSIONS: AD is independently associated with an increased risk of stroke and MI, especially in male subjects and ischemic stroke and the risk is associated with the severity of AD.

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

BACKGROUND: Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. METHODS: We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. RESULTS: Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P < 0.001), and the number of negative sentinel lymph nodes (OR = 0.686, 95% CI 0.575-0.817; P < 0.001) were independent statistically significant predictors of non-sentinel lymph node metastasis. Furthermore, luminal B (OR = 3.311, 95% CI 1.593-6.884; P = 0.001) and HER2 overexpression (OR = 4.308, 95% CI 1.097-16.912; P = 0.036) were independent and statistically significant predictor of non-sentinel lymph node metastasis versus luminal A. A regression model based on the results of multivariate analysis was established to predict the risk of non-sentinel lymph node metastasis, which had an AUC of 0.8188. The model was validated in the validation cohort and showed excellent diagnostic performance. CONCLUSIONS: The mathematical prediction model that incorporates five variables including breast cancer molecular subtype demonstrates excellent diagnostic performance in assessing the risk of non-sentinel lymph node metastasis in sentinel lymph node-positive patients. The prediction model could be of help surgeons in evaluating the risk of non-sentinel lymph node involvement for breast cancer patients; however, the model requires further validation in prospective studies.

Comparisons of the therapeutic effects of three different routes of bone marrow mesenchymal stem cell transplantation in cerebral ischemic rats.

Bone marrow mesenchymal stem cells (BMSCs) are mainly administered via three routes: intra-arterial, intravenous and intracerebral. It has been reported that BMSC administration via each route ameliorates the functional deficits after cerebral ischemia. However, there have been no comparisons of the therapeutic benefits of BMSC administration through different delivery routes. In this study, we injected BMSCs into a rat model of transient middle cerebral artery occlusion (MCAO) through the intra-arterial, intravenous, or intracerebral route at day 7 after MCAO. Control animals received only the vehicle. Neurological function was assessed at post-ischemic days (PIDs) 1, 7, 14, 21, 28 and 35 using behavioral tests (modified Neurological Severity Score (mNSS) and the adhesive removal test). At PID 35, the rat brain tissues were processed for histochemical and immunohistochemical staining. Our results showed that BMSC transplantation via the intra-arterial, intravenous, and intracerebral routes induced greater improvement in neurological functions than the control treatments; furthermore, the intra-arterial route showed the greatest degree and speed of neurological functional recovery. Moreover, BMSCs treatment through each route enhanced reconstruction of axonal myelination in the area of the corpus callosum on the infarct side of the cerebral hemisphere, increased the expression of SYN and Ki-67, and decreased the expression of Nogo-A in the brain. These effects were more apparent in the intra-arterial group than in the intravenous and intracerebral groups. These data suggest that BMSCs transplantation, especially through intra-arterial delivery, can effectively improve neurological function intra-arterial. The underlying mechanism may include the promotion of synaptogenesis, endogenous cell proliferation, and axonal regeneration.

Aquaporin3 is required for FGF-2-induced migration of human breast cancers.

PURPOSE: The aquaporin (AQP) family consists of a number of small integral membrane proteins that transport water and glycerol. AQPs are critical for trans-epithelial fluid transport. Recent reports demonstrated that AQPs, particularly AQP1 and AQP5, are expressed in high grade tumor cells of a variety of tissue origins, and that AQPs are involved in cell migration and metastasis. Based on this background, we examined whether AQP3, another important member of the AQP family, could facilitate cell migration in human breast cancers. METHODS: Potential role of AQP3 was examined using two representative breast cancer cell lines (MDA-MB-231 and Bcap-37). Briefly, AQP3 expression was inhibited with a lentivirus construct that stably expressed shRNA against the AQP3 mRNA. AQP3 expression inhibition was verified with Western blot. Cell migration was examined using a wound scratch assay in the presence of fibroblast growth factor-2 (FGF-2). In additional experiments, AQP3 was inhibited by CuSO4. Fibroblast growth factor receptor (FGFR) kinase inhibitor PD173074, PI3K inhibitor LY294002, and MEK1/2 inhibitor PD98059 were used to dissect the molecular mechanism of FGF-2 induced AQP3 expression. RESULTS: FGF-2 treatment increased AQP3 expression and induced cell migration in a dose dependent manner. Silencing AQP3 expression by a lentiviral shRNA inhibited FGF-2 induced cell migration. CuSO4, a water transport inhibitor selective for AQP3, also suppressed FGF-2-induced cell migration. The FGFR kinase inhibitor PD173074, significantly inhibited FGF-2-induced AQP3 expression and cell migration. The PI3K inhibitor LY294002 and MEK1/2 inhibitor PD98059 inhibited, but not fully blocked, FGF-2-induced AQP3 expression and cell migration. CONCLUSIONS: AQP3 is required for FGF-2-induced cell migration in cultured human breast cancer cells. Our findings also suggest the importance of FGFR-PI3K and FGFR-ERK signaling in FGF-2-induced AQP3 expression. In summary, our findings suggest a novel function of AQP3 in cell migration and metastasis of breast cancers.

[Effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells].

OBJECTIVE: To investigate the effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells. METHODS: Gefitinib was used in concentrations of 0 micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L and 20 micromol/L, respectively. Phosphorylation levels of EGFR and Akt were analyzed by Western blot. The capability of migration was measured by scratch test and Boyden chamber assay. Microfilaments (cell skeleton ) remolding and polarization were evaluated by immunofluorescence microscopy. RESULTS: Comparing with the control group (0 micromol/L gefitinib), gefitinib effectively inhibited the phosphorylation of EGFR and its downstream key proteins, and the effect displayed an obvious dose-effect relationship. At 24 hours after wound scratch, the cell migration distance of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was (36.3 +/- 4.0) microm, (30.3 +/- 3.8) microm, (26.8 +/- 3.3) microm, (17.0 +/- 2.6) microm, and (11.0 +/- 2.5) microm, respectively. At 3.5 hours after Boyden chamber assay, the cell count of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was 69.2 +/- 7.0, 51.8 +/- 7.5, 43.8 +/- 8.7, 30.6 +/- 4.8, and 28.4 +/- 3.4, respectively. Compared with the control group (0 micromol/L gefitinib), gefitinib could significantly prolong the wound-healing time and decrease the migrating cell count (P < 0.05), and significantly inhibit the lamellipodium formation, cell skeleton remolding and changes of the cytoskeleton polarization. CONCLUSIONS: Gefitinib can reduce the migration capacity of triple-negative breast cancer cells through inhibiting phosphorylation of EGFR/PI3K/Akt pathway, suppressing the cell skeleton (microfilaments) remolding and changes of its polarization.

[Relationship between SLP-2 expression and prognosis in laryngeal squamous cell carcinoma and mammary invasive carcinoma].

OBJECTIVE: To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis. METHODS: RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed. RESULTS: LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors. CONCLUSIONS: A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.