Aims To synthesize acetylated low molecu-lar weight heparin( ALMWH) and to detect its physico-chemical properties and antineoplastic activity. Meth-ods LMWH was prepared by degradation of UFH with sodium periodate oxidation and sodium borohydride re-duction, then the LMWH was acetylated by acetic an-hydride where N, N′, -dicyclohexylcarbodiimide ( DCC ) and 4-dimethylaminopyridine ( DMAP ) were used as catalysts. X-ray diffraction(XRD)and Differ-ential Scanning Calorimetry ( DSC ) of ALMWH were obtained. The antiproliferative activity and anti-inva-sive activity were determined on MDA-MB-231 and MCE-7 human breast cancer cells. Results XRD a-nalysis showed that the LMWH degraded from UFH and ALMWH synthesized by acetylation of LMWH be-longed to amorphous structure, however, their DSC curves were significantly different. Compared with LM-WH, ALMWH had more powerful capacity for binding water and lowering anticoagulant activity, more signifi-cantly ALMWH exhibited stranger anti-proliferative and anti-invasive activity than LMWH, especially when it was used in low concentrations. Conclusion The syn-thesized ALMWH possesses a low anticoagulant activi-ty, certain anti-proliferative, anti-invasive and anti-metastatic activity. This study provides a basic method for screening of antineoplastic drug with low toxicity.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Food additives are a kind of chemical substances added to food to enhance the taste,color and shelf life of food,and have become an indispensable part of the modern food industry.However,growing researches showed that synthetic chemicals used as food additives can be potentially harmful to health.Some food additives may be closely related to asthma,attention deficit hyperactivity disorder,heart disease,cancer,obesity and other health problems.In addition,some food additives may also interfere with hormone secretion,affect growth and development,and affect the healthy growth of children.This study reviews the damage effects of various food additives,such as preservatives,antioxidants,and colorants on body,and proposes the need to improve the safety evaluation of food additives from the perspective of the combined action of chemicals,in order to provide a scientific basis for food safety supervision and consumer health protection.

Objective To analyze the risk factors of cerebral microbleeds (CMBs) in acute cerebral infarction patients. Methods We consecutively included 255 acute cerebral infarction patients who were admitted in Neurology Department of the First Affiliated Hospital of Fujian Medical University from January 2014 to December 2016. According to the number and location of CMBs, the patients were divided into infratentorial, cortical and deep cerebral groups, each of which included non-mild and moderate-severe subgroups. The differences of the level of glomerular filtration rate (eGFR) and some common arteriosclerotic risk factors were analyzed between subgroups, and the multiple logistic regression analysis was performed. Results A total of 140 subjects (54.9%) had CMBs. In the infratentorial group, the proportion of patients who were with low eGFR level in the moderate-severe CMBs subgroup was higher than in the non-mild CMBs subgroup (P=0.024). The low eGFR level (OR=3.874, 95% CI:1.261～11.901, P=0.018) and the long duration of hypertension (OR=2.128, 95%CI: 1.004～4.510, P=0.018) were the independent risk factors of the moderate-severe infratentorial CMBs. Conclusion The low eGFR level and long duration of hypertension are risk factors for the moderate and severe infratentorial CMBs after acute ischemic stroke.

Objective To preliminarily explore the clinical features,treatment,and outcomes of moyamoya disease in the elderly.Methods The clinical data of the elderly patients with moyamoya disease (aged ＞ 60 years) admitted to the Department of Neurosurgery,the 307th Hospital of PLA from May 2007 to July 2016 were collected retrospectively.Their clinical features,imaging features,and surgical outcomes were analyzed.Results A total of 68 patients were enrolled,including 35 females (51.47％) and 33 males (48.53％).The ratio of male to female was 1:1.06.The age at the time of diagnosis of moyamoya disease was 62.82 ±3.08 years.Fifty-two patients (76.5％) had vascular risk factors.The most common clinical manifestation was cerebral ischemia (n =61,89.7％).Thirty of them (44.1％) presented as transient ischemic attack.The Suzuki staging of most patients was 4-6 (71.6％),12 patients (17.6％) complicated with posterior cerebral artery stenosis or occlusion.Thirty-one patients were treated with encephalo-duroarterio-synangiosis (EDAS).Among them,17 patients underwent bilateral surgery and 14 underwent unilateral surgery.The incidence of perioperative infarction or hemorrhage was 5.6％ (2 patients developed cerebral infarction and 1 patient developed cerebral hemorrhage);37 patients received conservative treatment.During the follow-up period,5 patients developed cerebral infarction (1 in the surgical treatment group and 4 in the conservative treatment group);there was no significant difference between the 2 groups.There were no significant differences in age,sex,vascular risk factor,clinical symptoms,and preoperative modified Rankin Scale (mRS) scores between the 2 groups.Cerebral angiography was performed 6-9 months after operation in the surgical treatment group.A total of 24 cerebral hemispheres were evaluated by Matsushima typing,of which 17 (70.8％) were excellent.During the follow-up period,the proportion of patients with clinical outcome excellent (the mRS score was 0) (Z =-5.268,P ＜ 0.00l) and clinical improvement (the mRS score was improved ≥ 1 compared to the baseline) (Z =-3.780,P ＜ 0.001) were significantly higher than the conservative treatment group.Conclusions The clinical symptoms of old patients with moyamoya disease were mainly cerebral ischemia.Most of them had vascular risk factors,and the imaging manifestations showed higher Suzuki staging.The perioperative risk of EDAS in the old patients with moyamoya disease was lower.It might be an effective method to prevent clinical symptoms progress and improve the outcomes.

Objective To summarize the phenotypic spectrum of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Fujian population,evaluate the efficiency of the scale and try to adjust it.Methods Thirty-eight CADASIL patients and 64 CADASIL-like patients were recruited based on the CADASIL scale and gene tests,who visited the First Affiliated Hospital of Fujian Medical University and Fujian Neurology Research Institute from May 2011 to November 2017.Their clinical and neuroimaging characteristics were analyzed.Results The migraine,migraine with aura,transient ischemic attack / stroke,early onset age,psychiatric disturbances,cognitive decline,leukoencephalopathy,subcortical infarcts showed no statistically significant differences between the two groups.Instead,compared with CADASIL-like patients (10/64,15.6％;47/64,73.4％;10/64,15.6％),CADASIL patients demonstrated higher percentages of temporal pole involvements (13/38,34.2％;x5=4.716,P=0.030),external capsule involvements (36/38,94.7％;P=0.008) and family history in at least two generations (13/38,34.2％;x2=4.716,P=0.030).According to the scale,the scores showed statistically significant difference between CADASIL (14.84 ± 3.03) and CADASIL-like patients (13.34 ± 3.31;t=2.282,P=0.025) with an area under receiver operating characteristic curve of 0.622.Conclusions CADASIL showed no specific symptoms in Fujian population.The neuroimaging features were proposed to be focused on,especially the external capsule involvements.CADASIL scale could improve diagnostic efficiency,but still needs to be adjusted for Fujian population.The weight value of migraine,migraine with aura and cognitive decline was suggested to be decreased.

Objective:To investigate the safety and efficacy of Tubridge flow diverter for the treatment of recurrent internal carotid blood blister-like aneurysms after stent-assisted embolization.Methods:From June 2018 to April 2021, patients with recurrent internal carotid blood blister-like aneurysms treated with Tubridge flow diverter in the Department of Neurosurgery, Changhai Hospital, Naval Medical University were enrolled retrospectively. The perioperative safety, immediate postoperative and follow-up results were analyzed.Results:A total of 6 patients with recurrent internal carotid blood blister-like aneurysm after stent-assisted embolization were enrolled. The time interval from the first stent-assisted embolization to Tubridge placement was 14 to 90 d. Tubridge implantation alone was used in 4 patients, and Tubridge was implanted in the other 2 patients after the coils were packed. There were no complications during the perioperative period, and no rebleeding was observed after clinical follow-up for 5 to 36 months. Five patients were followed up by angiography for 1-3 months, and the aneurysms disappeared completely.Conclusion:Tubridge flow diverter for the treatment of recurrent internal carotid blood blister-like aneurysms is safe and effective.

Objective:To establish the fingerprints of Microctis Folium by ultra high performance liquid chromatography (UPLC); To determine the contents of three flavonoids in the Microctis Folium; To evaluate the quality difference of Microctis Folium from different producing areas. Methods:The fingerprints were performed on Agilent ZORBAX SB C18 column (2.1 mm×150 mm,1.8 μm). The mobile phase was acetonitrile - 0.1 % acetic acid solution with gradient elution at a flow rate of 0.30 ml/min. The column temperature was 30 ℃ and the detection wavelength was 315 nm. The common fingerprint peaks were identified by UPLC-mass spectrometry, and the identification results were confirmed by comparison of reference materials. Waters Cortecs T3 C18 chromatographic column (2.1 mm × 100 mm,1.6 μm) was used for content determination. The mobile phase was methanol-0.1 % formic acid solution with gradient elution at a flow rate of 0.35 ml/min. The column temperature was 30 ℃ and the detection wavelength was 339 nm. The contents of vitexin, isovitexin and narcissoside in 15 batches of Microctis Folium from different habitats were determine. Results:There were 11 common peaks in the fingerprint of Microctis Folium. Identified by mass spectrometry and confirmed by reference substance,10 chemical components were identified, including caffeic acid, p-hydroxycinnamic acid, ferulic acid, vitexin, isovitexin, kaempferol-3-O-rutoside, astragaloside, narcissoside, isorhamnetin-3-O-glucoside and linden glycoside. The similarity between the fingerprints of 15 batches of Microctis Folium and the control fingerprint was greater than 0.95, indicating that the overall similarity of the fingerprints of Microctis Folium from different producing areas was high. The total contents of three active components were 3.23-5.64 mg/g in Yangjiang City, Guangdong, 3.60-5.78 mg/g in Zhanjiang City, Guangdong, 4.68-5.73 mg/g in Yulin City, Guangxi and 3.87-5.21 mg/g in Wuzhishan City, Hainan . There was no significant difference in the content of three active components in different producing areas. Conclusion:The fingerprints and the determination method established in the study are stable and feasible, which can be used for the quality evaluation of Microctis Folium.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

Objective:To investigate the clinicopathological features and prognosis of pleomorphic giant cell adenocarcinoma (PGCA) of the prostate, and to strengthen the understanding of this rare variant.Methods:From January 2009 to December 2019, 383 pathological samples of prostate adenocarcinoma with Gleason scores of 8-10 were selected from the First Affiliated Hospital, Army Medical University. PGCA was screened by reviewing the histomorphology of hematoxylin and eosin stained sections. Then the expression of prostate specific markers and mismatch repair (MMR) proteins of PGCA were detected by immunohistochemistry (IHC), and microsatellite instability (MSI) status was detected through polymerase chain reaction (PCR)-capillary electrophoresis. Meanwhile, the clinicopathological characteristics, diagnosis, treatment and prognosis of PGCA were summarized and analyzed along with those reported in the literature.Results:Three patients with PGCA of the prostate were 68, 63 and 71 years old respectively, and case 1 had a history of transurethral resection of the prostate and oral bicalutamide 3 months before surgery. All 3 patients underwent radical prostatectomy and received endocrine therapy, radiotherapy and/or chemotherapy, and died at 18, 23, and 10 months after surgery, respectively. Histologically, both the usual prostate adenocarcinoma with Gleason score of 9-10 and the pleomorphic giant cell component with anaplastic characteristics were observed in 3 tumors, and the latter accounted for 90%, 10%, and 20%, respectively. Immunohistochemical staining showed that both components expressed epithelial markers (CK, CK8/18) and prostate-specific markers (NKX3.1, PSA, P504S) to varying degrees, and the expression of MMR proteins (MSH2, MSH6, MLH1 and PMS2) were not defective. MSI was not detected in the usual prostate adenocarcinoma and pleomorphic giant cell components obtained by microdissection in 3 cases. Combined with 10 cases reported in the literature, there were totally 13 cases of PGCA for reviewing. The patients were 45-81 years old, the average age was 66 years old, and the median age was 66 years old. During the follow-up period of 3-36 months, 7 cases relapsed/metastasized, 6 cases died within 23 months after diagnosis, and 4 of which died within 1 year.Conclusions:PGCA is a newly recognized rare variant of prostate adenocarcinoma. At present, all cases are accompanied with high-grade usual prostate adenocarcinoma with Gleason score of 9-10, but it is different from the latter in pathological morphology and clinical manifestations, by presenting high invasiveness and poor prognosis. PGCA is not sensitive to conventional endocrine therapy, radiotherapy or chemotherapy. Accurate diagnosis of PGCA is helpful to judge the prognosis of patients and guide the treatment.