Objective To study improvement of neural function by stereotaxic transplantation of adipose-derived stem cells (ADSC) into lateral cerebral ventricle after intracerebral hemorrhage in rats and its mechanism. Methods ADSC were cultured and proliferated in vitro, which had been marked with Brdu for 48 h before transplantation. The rat caudate nucleus hemorrhage (ICH) models were divided into 2 groups. ADSC were stereotaxically transplanted into the right lateral ventricles in ADSC group, and equal volume of saline was transplanted into control group. The score of neurological behavior were evaluated at modeling and 1, 3, 7, 14, 28 days after transplantation respectively.Double-staining immunofluorescence technique was used to detect Brdu-positive cells and the differentiation of neurons and astrocytes. In accordance with the instructions of TUNEL kit, cell apoptosis, and the expression of VEGF and angiogenesis were assayed. Results In vitro ADSC expressed undergo osteogenic and adipogenic differentiation. Compared with the control group, ADSC group had better motor function at 3, 7, and 14 days (P＜0. 05). Double-staining immunofluorescence showed mostly grafted Brdu-reactive ADSC had migrated to the hematoma zone, and some survivedand expressed Neun of Gfap. TUNEL analysis revealed that, 3 days after transplantation, the number of apoptotic cells in ADSC group was significantly less than in the control group (P＜0. 05). Three days after transplantation, VEGF expression levels in ADSC group were significantly higher than in the control group (P＜0. 05). Conclusion ADSC stereotaxially transplanted into the lateral ventricle can survive and differentiate into neuron-like cells. ADSC transplantation may reduce apoptosis and secret VEGF to promote the angiogenesis, and improve neural functional in intracerebral hemorrhage rats.

Objective: To investigate the predictors of death after endovascular mechanical thrombectomy (EMT) in patients with acute vertebrobasilar occlusive stroke (VBOS). Methods: Patients with acute VBOS treated with EMT in Wuhan No. 1 Hospital were enrolled retrospectively. The demographic and clinical data were collected. According to whether the patients died at 90 d after procedure, they were divided into survival group and death group. The demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent risk factors for death at 90 d after EMT. Results: A total of 47 patients were enrolled. The median age was 62 years, 34 were males (72.3%), the median baseline National Institutes of Health Stroke Scale (NIHSS) score was 16, 42 patients (89.4%) had recanalization (modified Thrombolysis in Cerebral Infarction[mTICI] 2b/3 grade), and 12 (25.5%) died within 90 d after procedure. Univariate analysis showed that the baseline NIHSS score (26 [21-28]vs. 12 [5-23]; Z=-3.165, P=0.002), percentage of neutrophil (81.61% ±11.82% vs. 72.20% ±12.09%; t=-2.137, P=0.033), neutrophil/lymphocyte ratio (10.54±7.17 vs. 4.98±3.57; t=-2.393, P=0.017), and incidence of sICH (25.0% vs. 2.9%; χ²=5.627, P=0.018) in the death group were significantly higher than those in the survival group, while the percentage of lymphocyte (12.00%±9.04% vs. 20.67%±10.39%; t=-2.429, P=0.015) was significantly lower than that of the survival group. Multivariate logistic regression analysis showed that high baseline NIHSS score (odds ratio [OR] 1.243, 95% confidence interval [CI] 1.046-1.318; P=0.038), high neutrophil/lymphocyte ratio (OR 1.278, 95% CI 1.002-1.630; P=0.049) and symptomatic intracranial hemorrhage (OR 5.088, 95% CI 1.065-38.718; P=0.046) were the independent predictors for death. Conclusion High baseline NIHSS score, high neutrophil/lymphocyte ratio and symptomatic intracranial hemorrhage are the independent predictors for death within 90 d after EMT in patients with acute VBOS.

Objective:To explore the clinical characteristics of superior mesenteric artery ischemic diseases.Methods:The clinical and followup data of 141 hospitalized patients with ischemic disease of superior mesenteric artery in the Affiliated Hospital of Southwest Medical University from 1999 to 2021 were reviewed.Results:There were 99 males (70.2%) and 42 females (29.8%). The average age of the patients was (63.75±13.16) years; 127 patients (90.1%) complained abdominal pain.The number of all-cause deaths in the perioperative period was 27 (19.1%). ROC curve analysis showed that the optimal cutoff value of the age with predictive value was 64.5 years. The results of multivariate COX regression analysis showed that age ≥65 years old ( HR=3.855, 95% CI: 1.739-8.545), neutrophil count ( HR=1.072, 95% CI: 1.018-1.130), heart failure ( HR=2.863, 95% CI: 1.332-6.154), creatinine ( HR=1.009, 95% CI: 1.003-1.015), D-Dimer ( HR=1.112, 95% CI: 1.025-1.205) was an independent risk factor for all-cause death from superior mesenteric artery ischemic disease. Long-term survival rate of SMAD group was significantly higher than that of other SMAID; By comparing the clinical characteristics of different SMAID, neutrophil count, neutrophil ratio, D-dimer of SMAE group and SMAT group were significantly higher than that of SMAD group and ASSMA group. Conclusions:SMAID usually occurs in elderly men over 65 years old, with abdominal pain as the main symptom and often accompanied by hypertension. Risk factors included age, increased WBC count and D-dimer; The neutrophil count, neutrophil ratio, D-dimer in SMAE and SMAT group were significantly higher than that of SMAD and ASSMA group.

Objective:To compare the clinical outcomes of endovascular therapy in acute stroke patients with anterior circulation tandem occlusions caused by atherosclerosis or dissection.Methods:A retrospective cohort study. A total of 98 patients with anterior circulation tandem lesions undergoing endovascular therapy in the Wuhan NO.1 Hospital (March 2016 to March 2022) were analyzed. Median age was 64(55,71) years old, and 82.7% (81/98 cases) were males. According to the lesion etiology, the patients were divided into atherosclerosis and dissection groups. The differences in clinical outcomes between the two groups were investigated, including favorable 90-day functional outcome (modified Rankin Scale score of 0-2), successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction score of 2b-3), symptomatic intracranial hemorrhage, stroke-associated pneumonia, 90-day all-cause mortality, and average hospitalization days. Logistic regression analysis was used to adjust for potential confounders affecting functional outcomes in both groups, and to determine odds ratios and 95% confidence intervals.Results:Seventy-one patients were grouped into the atherosclerotic cause and 27 into the dissection cause cohorts. The rate of favorable 90-day functional outcome was 43.7% (31/71 cases) in the atherosclerosis group versus 55.6% (15/27 cases) in the dissection group (adjusted odds ratio=1.339; 95% confidence interval, 0.374-4.798; P=0.654). No significant differences were found in other clinical outcomes between the two groups (all P>0.05). Conclusion:The clinical prognosis of patients with tandem lesions caused by atherosclerotic stenosis or artery dissection was similar after endovascular therapy. Future studies are still needed to verify our results.

Atypical and malignant meningiomas are characterized by high invasiveness and local recurrence.Traditional treatments such as surgery,radiotherapy and chemotherapy have limited effects.Recently,with the further study of the pathogenesis of meningioma and the development of molecular biology techniques,some new biomarkers have been found to play important roles in development and malignant progression of meningioma.Several genetic and epigenetic factors have been identified as contributing to the malignant progression of meningioma.Genetic factors include multiple phenotypic changes such as abnormal cell proliferation,increased cell invasiveness,angiogenesis,apoptosis inhibition,and changes in telomerase activity.And the discovery of biomarkers provides references for early diagnosis,molecular targeted therapy and prognosis assessment of high-grade meningiomas.

BACKGROUNDEndostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.

METHODSFour hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .

RESULTSOf 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .

CONCLUSIONSThe addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .

Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds, hydroxylamines or aromatic amines, most of which are carcinogenic and mutagenic agents. Inhibition of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon, so as to prevent colon diseases. In this study, the inhibitory effects of 55 herbal medicines against Escherichia coli(E. coli) nitroreductase (EcNfsA) were examined. Compared with other herbal extracts, Syzygium aromaticum extract showed superior inhibitory potency toward EcNfsA mediated nitrofurazone reduction. Then, the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were evaluted. Compared with other tested natural compounds, ellagic acid, corilagin, betulinic acid, oleanic acid, ursolic acid, urolithin M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA, with IC₅₀ values ranging from 0.67 to 28.98 mol·L^-1. Furthermore, the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA (K_i < 2 μmol·L ^-1) in a competitively inhibitory manner, which created strong interactions with the catalytic triad of EcNfsA. In summary, our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum, where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacterial nitroreductase.
Ellagic Acid/pharmacology* ; Escherichia coli ; Kinetics ; Nitroreductases/pharmacology* ; Plant Extracts/pharmacology* ; Syzygium

OBJECTIVETo evaluate the association between the two single nucleotide polymorphisms located in catechol-O-methyltransferase (COMT) gene and type 2 diabetes mellitus (T2DM)in Han population in Guangdong province.

METHODSTwo tagSNPs (rs4646312 and rs4680) were picked out from COMT gene. Using the SNPscan(TM) Kit, SNP genotyping was then performed, in two cohorts, including 595 cases and 725 controls. Finally, Chi-square test, logistic regression model and other methods were employed for statistical analysis.

RESULTSThe frequencies of TT, CT and CC of rs4646312 appeared to be 304(51.1%), 234(39.3%)and 57 (8.6%) in cases, 323 (44.6%), 319 (44.0%) and 83(11.4%)in controls, respectively. The frequencies of GG,GA and AA of rs4680 were 311(52.4%), 236 (39.8%) and 46(7.8%)in cases, 417(57.7%), 265 (36.6%) and 41 (5.7%) in controls, respectively.

RESULTSshowed that SNP rs4646312 was significantly associated with T2DM both in allelic association analysis (P = 0.020,OR = 1.26, 95%CI:1.04-1.53)and in recessive model (P = 0.022, OR = 1.35, 95% CI:1.05-1.74)after adjustment for sex,BMI and TG. The association between rs4680 and T2DM was not significant, but BMI was remarkably different among the three genotypes of rs4680 after controlling for other factors.

CONCLUSIONSNP rs4646312 of COMT gene was associated with the increased risk of T2DM in Han population in Guangdong province. However, rs4680 was not significantly associated with T2DM.

Adult ; Aged ; Alleles ; Case-Control Studies ; Catechol O-Methyltransferase ; genetics ; Diabetes Mellitus, Type 2 ; etiology ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.
Adenocarcinoma, Mucinous/therapy* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Appendiceal Neoplasms/surgery* ; Colorectal Neoplasms/pathology* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures/methods* ; Female ; Humans ; Hyperthermia, Induced/methods* ; Male ; Middle Aged ; Peritoneal Neoplasms/secondary* ; Retrospective Studies ; Survival Rate