Isolation and neuronal apoptosis inhibitory property of bacoside-A3 via downregulation of ß-amyloid induced inflammatory response.

Alzheimer's disease is one of the neurodegenerative disorders caused by neuronal degeneration and apoptosis in brain. Bacoside A and B isolated from the Bacopa monniera plant are responsible for cognitive effects. These compounds repair damaged neurons by promoting activity of kinases, synaptic activity restoration, and improvement of nerve transmission. The present study explored the effect of bacoside-A3 on ß-amyloid-induced reduction of U87MG cell viability, generation of oxidative radicals, and activation of nuclear factor-κB. The U87MG cells were stimulated with ß-amyloid (10 µM) after 24 h of bacoside-A3 pretreatment or without pretreatment to induce characteristics of Alzheimer disease in vitro. Sulforhodamine B (SRB) assay was used to count viable cells and ELISA kit for analysis of PGE2 secretion. The pretreatment with bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell proliferation. Pretreatment of U87MG cells with bacoside-A3 prior to ß-amyloid stimulation suppressed generation of ROS in a concentration-based manner. The ß-amyloid-mediated formation of iNOS in U87MG cells was suppressed by bacoside-A3 in a dose-based manner. The ß-amyloid-mediated PGE2 secretion was suppressed by bacoside-A3 pretreatment in U87MG cells in the dose-based manner. The overexpression of COX-2 by ß-amyloid stimulation was suppressed in bacoside-A pretreated cells in the dose-based manner. The bacoside-A3 pretreatment prevented nuclear translocation of NF-κB in U87MG cells in the dose-based manner. In summary, bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell viability, inhibited generation of oxidative radicals, PGE2, and synthesis of iNOS. Therefore, bacoside-A3 has therapeutic potential for Alzheimer disease and further in vivo studies need to be performed.

Prognostic Value of Diffusion-Weighted Imaging (DWI) Apparent Diffusion Coefficient (ADC) in Patients with Hyperacute Cerebral Infarction Receiving rt-PA Intravenous Thrombolytic Therapy.

BACKGROUND The aim of this study was to investigate the potential value of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in the prognosis of patients with hyperacute cerebral infarction (HCI) receiving intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). MATERIAL AND METHODS From June 2012 to June 2015, 58 cases of HCI (<6 h) undergoing rt-PA intravenous thrombolytic therapy (thrombolysis group) and 70 cases of HCI (<6 h) undergoing conventional antiplatelet and anticoagulant therapy (control group) in the same period were collected. DWI was conducted on all the subjects, and ADC maps were generated with Functool software to quantify ADC value. The clinical outcomes of HCI patients were observed for 3 months, and prognostic factors were analyzed. RESULTS Before thrombolysis treatment, the lesion area presented high signal intensity on DWI map and low signal intensity on ADC map, and gradually weakened signal intensity on DWI map and gradually enhanced signal intensity on ADC map were observed after thrombolysis. The ADC values of the thrombolysis group were significantly higher than those of the control group after treatment (24 h, 7 d, 30 d, and 90 d) (all P<0.05), and the ADC and rADC values in the thrombolysis group gradually increased over time (all P<0.05). Multiple logistic regression analysis showed that baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline rADC value, and stroke history were the independent factors for the prognosis of HIC patients with thrombolysis (all P<0.05). CONCLUSIONS The values of ADC and rADC may provide guidance in the prognosis of HCI patients receiving rt-PA, and the baseline rADC value is the protective factor for the prognosis of HCI patients receiving rt-PA.

MicroRNA profile of tumorigenic cells during carcinogenesis of lung adenocarcinoma.

To obtain microRNA (miRNA) profile and clarify their biological function in tumorigenic Sca-1(+) CD34(+) cells during carcinogenesis of lung adenocarcinoma. After intranasal infection with recombinant Adeno-Cre viruses (AdV-Cre), lung adenocarcinoma was identified pathologically in Lox-stop-lox Kras (LSL-Kras) G12D mice. Sca-1(+) CD34(+) cells were sorted by flow cytometry and tested for tumor-initiating ability, self-renewal and tumorigenicity. MiRNA profiles were obtained using microarray and further confirmed by real-time RT-PCR (qRT-PCR). MiRNA functions were predicted bioinformatically, and miR-294 function was verified to explore its role in tumor migration and invasion. Lung adenocarcinoma was induced in LSL-Kras G12D mice within 30 days. In vivo, the tumorigenicity of Sca-1(+) CD34(+) cells was 25 times stronger than Sca-1(-) CD34(-) cells. During tumorigenesis of lung adenocarcinoma, the expression of 145 miRNAs in Sca-1(+) CD34(+) cells increased and 72 miRNAs decreased (P < 0.01). Four successively up-regulated miRNAs (miR-15a*, miR-203, miR-294 and miR-295*) and three successively down-regulated ones (miR-19b, miR-483 and miR-615-5p) were identified. Among them, miR-294 could constitutively bind to 3'-UTR of matrix metalloproteinase 3 (MMP3), and down-regulate MMP3 protein expression. MiR-294 also significantly inhibited migration and invasion of Lewis lung cancer cells. MiRNAs are characteristically expressed in tumor-initiating Sca-1(+) CD34(+) cells of lung adenocarcinoma, and may play important roles during the carcinogenesis of lung adenocarcinoma.

Acute Effects of Haloperidol, Amisulpride, and Quetiapine on Bone Turnover Markers in Patients With Schizophrenia.

OBJECTIVE: This prospective study sought to compare the acute effects of haloperidol, amisulpride, and quetiapine on serum markers of bone formation and resorption in relatively young patients with minimal previous exposure to antipsychotic drugs. METHODS: Patients included in the study were randomly assigned to receive haloperidol, amisulpride, or quetiapine monotherapy in an open-label manner. Serum osteocalcin (OC, a marker of bone formation), C-terminal peptide of type I collagen (CTX, a marker of bone resorption), prolactin (PRL), estradiol, and testosterone were measured in 70 patients at baseline and after 4 weeks of antipsychotic treatment. RESULTS: A repeated-measures analysis of variance revealed a significant difference in CTX levels and in the OC to CTX ratio between treatment groups (F = 4.481, P < 0.05; F = 8.114, P < 0.01). After 4 weeks of treatment, only the amisulpride group had significantly increased CTX levels and decreased OC/CTX. In addition, an obvious increase in PRL level and a reduction of sex hormone secretion after amisulpride treatment were found. No significant changes in bone turnover were observed in the haloperidol or quetiapine groups. Notably, a positive correlation between the CTX change to the change in PRL after treatment (r = 0.255, P < 0.05) was observed. CONCLUSIONS: The PRL-raising antipsychotic drug amisulpride influenced bone turnover balance very early in the course of treatment, which may require long-term monitoring of bone metabolism. Bone resorption marker changes induced by acute antipsychotic drug treatment are likely related to increased PRL levels.

Synthesis, structure analysis, antitumor evaluation and 3D-QSAR studies of 3,6-disubstituted-dihydro-1,2,4,5-tetrazine derivatives.

3,6-Diaryl-dihydro-1,2,4,5-tetrazine derivatives were synthesized and their structures were confirmed by single-crystal X-ray diffraction. Monosubstituted dihydrotetrazines are the 1,4-dihydro structure, but disubstituted dihydrotetrazines are the 1,2-dihydro structure. The results of further research indicated there may be a rearrangement during the synthesis process of disubstituted dihydrotetrazines. Their antitumor activities were evaluated against A-549 and P388 cells in vitro. The results showed several compounds to be endowed with cytotoxicity in the low micromolar range. Two compounds were highly effective against A-549 cell and IC50 values were 0.575 and 2.08 µM, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 37 1,2,4,5-tetrazine derivatives with antitumor activity against A-549 cell. Models with good predictive abilities were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.744 and 0.757, respectively. Conventional r(2) values were 0.978 and 0.988, respectively, the predicted R(2) values were 0.916 and 0.898, respectively. The results provide the tool for guiding the design and synthesis of novel and more potent tetrazine derivatives.

[Analysis of surgical treatment of soft tissue sarcomas of the adductor compartment].

OBJECTIVE: To review the outcomes and complications of 21 consecutive patients with soft tissue sarcomas of the adductor compartment treated in our hospital from July 2006 to March 2012. METHODS: Medical records of 21 patients who underwent resection of soft tissue sarcomas of the adductor compartment were reviewed. Eight of the patients had primary operation, other eight had secondary radical excision, and five were admitted for tumor recurrence after operation in local hospitals. Six cases used gracilis or sartorius muscle to fill the cavity after removal of adductor muscle group. Fifteen patients underwent adjuvant treatment including radiotherapy and/or chemotherapy. RESULTS: Seven patients (33.3%) developed wound complications. Five required further surgery and two received dressing changes. All the patients were followed up for 3 to 60 months. During the follow-up period, no tumor recurrence was found in all the patients, only one case had multiple bone and pulmonary metastases, and two cases died (one for pulmonary metastasis at 11 months after surgery, and the other died of heart disease at 36 months post operation). CONCLUSIONS: Good local control rate can be achieved in patients with soft tissue sarcomas of the adductor compartment by using adductor muscle group resection, but it carries a relatively high rate of wound complications requiring proper management.

Robust, Flame-Retardant, and Anti-Corrosive Waterborne Polyurethane Enabled by a PN Synergistic Flame-Retardant Containing Benzimidazole and Phosphinate Groups.

Waterborne polyurethanes (WPUs) have attracted great interest owing to their environmentally friendly properties, and are wildly applied in production and daily life. However, waterborne polyurethanes are flammable. Up to now, the challenge remains to prepare WPUs with excellent flame resistance, high emulsion stability, and outstanding mechanical properties. Herein, a novel flame-retardant additive, 2-hydroxyethan-1-aminium (2-(1H-benzo[d]imidazol-2-yl)ethyl)(phenyl)phosphinate (BIEP-ETA) has been synthesized and applied to improve the flame resistance of WPUs, which has both phosphorus nitrogen synergistic effect and the ability to form hydrogen bonds with WPUs. The WPU blends (WPU/FRs) exhibited a positive fire-retardant effect in both the vapor and condensed phases, with significantly improved self-extinguishing performance and reduced heat release value. Interestingly, thanks to the good compatibility between BIEP-ETA and WPUs, WPU/FRs not only have higher emulsion stability, but also have better mechanical properties with synchronously improved tensile strength and toughness. Moreover, WPU/FRs also exhibit excellent potential as a corrosion-resistant coating.

[Value of intraoperative electron radiation therapy in the treatment of malignant bone or soft tissue tumors around the joints].

OBJECTIVE: To evaluate the value of intraoperative radiation therapy with electrons (ELIOT) in treatment of malignant bone or soft tissue tumors around the joints. METHODS: From October 2008 to April 2012, nineteen patients with malignant bone or soft tissue tumors around the joints were treated with ELIOT. The tumors were located around the knee joint in 8 patients, around the hip joint in 6 patients, around the elbow joint in 4 patients and around the shoulder joint in one patient. All of the patients underwent limb salvage surgeries. R0 resections were performed in 18 patients, while R1 resection was performed in one patient. The doses of intraoperative radiation ranged from 10 Gy to 22 Gy. The median dose was 19 Gy. More than one ELIOT fields were used in 10 patients because of the large tumor size. RESULTS: Seven patients suffered wound complications. No grade ≥ 3 acute toxicities were observed. One patient developed radiation ulcer and arterial fistula 15 months after surgery and ELIOT, and resulted in amputation finally (grade 4 late toxicity). The mean Musculoskeletal Tumor Society (MSTS) 93 score was 26.26 ± 4.04 (87.5% ± 13.5%), with excellent to good extremity functions in 18 patients (94.7%). Four patients had local recurrences. The estimated locoregional control rates at 1, 2, and 3 years were 81.9%, 73.7%, and 73.7%, respectively. Seven patients died of the diseases. The estimated overall survivals of the entire group of patients at 1, 2, and 3 years were 76.3%, 61.2%, and 51.0%, respectively. CONCLUSIONS: ELIOT is a safe and well-tolerable technique and could be widely used for patients with malignant bone or soft tissue tumors around the joints with acceptable rates of acute and late toxicity. There is positive significance for controlling the tumor local recurrence, preserving the joint function and improving survival quality.

[Damage control surgery for pancreatic injuries after blunt abdominal trauma].

OBJECTIVE: To summarize the management of pancreatic injuries after blunt abdominal trauma. METHODS: The clinical data of 42 patients with blunt pancreatic injury admitted from January 2001 to December 2010 was analyzed retrospectively. There were 38 male and 4 female patients, aging from 13 to 65 years with a mean of 31 years. The organ injury scaling of Committee of the American Association for the Surgery of Trauma (AAST grade): grade I in 3 patients, grade II in 12 patients, grade III in 9 patients, grade IV in 13 patients and grade V in 5 patients. The mean injury severity score was 27 ± 21. Patients above AAST grade II underwent peritoneal drainage and "three neostomy" (gastrostomy, jejunostomy and gallbladder) according to damage control theory. RESULTS: Thirty-eight patients got abdominal CT scanning with a positive rate of 79.9% (30/38). Forty patients underwent surgical procedures, and 2 patients with non-operative management. The surgical procedures include peritoneal drainage and "three neostomy" in 32 patients, pancreas suture or pancreatic tail resection in 6 patients, pancreatoduodenectomy or caudal pancreaticojejunostomy in 2 patients. Forty patients (95.2%) survived, 2 patients (4.8%) died and 16 patients (38.1%) had complications such as pancreatic fistula,pulmonary infection. CONCLUSIONS: Abdominal CT scanning will benefit the preoperative diagnosis of blunt pancreatic trauma. Although the survival rate of patients with blunt pancreatic trauma might be improved by using the damage control surgery, the management of damage control surgery also needs to be modified because of the high rate of complications.

Osteofibrous dysplasia-like adamantinoma: A case report and literature review.

Abstract background: Osteofibrous dysplasia-like adamantinoma (OFD-like adamantinoma), classical adamantinoma and dedifferentiated adamantinoma were previously considered to be three subtypes of adamantinoma of long bones. In the 5th edition of the World Health Organization (WHO) classification of bone tumors in 2020, OFD-like adamantinoma was newly proposed and classified as an intermediate-locally aggressive tumor in other mesenchymal tumors of bone. OFD-like adamantinoma is rare, accounting for only 0.4% of all primary bone tumors. OFD-like adamantinoma is often misdiagnosed due to the insufficient understanding of it. Here we report a case of OFD-like adamantinoma treated in our hospital with a literature review. Case presentation: The patient, a 14-year-old male, had swelling in his right leg with intermittent pain for one year. Plain radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. Based on the radiological and histological examinations, a diagnosis of OFD-like adamantinoma was suspected. After admission, the patient underwent tumor resection of the right tibia, free transplantation of the left fibula and internal fixation. After resection of the tumor, the wound recovered well, the vital signs were stable, and activity was normal. The patient has been followed up for more than a year with no recurrence or distant metastasis. Conclusion: OFD-like adamantinoma is a rare primary bone tumor with nonspecific clinical features. Imaging examination can demonstrate the lesion and help diagnosis. The pathological discovery of epithelioid tissue is the key evidence for diagnosis.

The landscape of gene mutations and clinical significance of tumor mutation burden in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.

BACKGROUND: The aim of this study was to evaluate the landscape of gene mutations and the clinical significance of tumor mutation burden (TMB) in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy. METHODS: A total of 68 patients with soft tissue sarcoma were included. Postoperative tumor tissue specimens from the patients were collected for DNA extraction. Targeted next-generation sequencing of cancer-relevant genes was performed for the detection of gene mutations and the analysis of TMB. Univariate analysis between TMB status and prognosis was carried out using the Kaplan-Meier survival analysis, and multivariate analysis was adjusted by the Cox regression model. RESULTS: No specific genetic mutations associated with soft tissue sarcoma were found. The mutation frequency of TP53, PIK3C2G, NCOR1, and KRAS of the 68 patients with soft tissue sarcoma were observed in 19 cases (27.94%), 15 cases (22.06%), 14 cases (20.59%), and 14 cases (20.59%), respectively. With regard to the analysis of TMB, the overall TMB of the 68 patients with soft tissue sarcoma was relatively low (median: 2.05 per Mb (range: 0∼15.5 per Mb)). Subsequently, TMB status was divided into TMB-Low and TMB-Middle according to the median TMB. Patients with TMB-Low and TMB-Middle were 37 cases (54.41%) and 31 cases (45.59%), respectively. Overall survival analysis indicated that the median overall survival of patients with TMB-Low and TMB-Middle was not reached, and 4.5 years, respectively (P=0.015). CONCLUSION: This study characterizes the genetic background of patients with STS soft tissue sarcoma. The TMB was of clinical significance for patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.

Structural, luminescent, and magnetic properties of three novel three-dimensional metal-organic frameworks based on hexadentate N,N'-bis(4-picolinoyl)hydrazine.

Three novel microporous three-dimensional (3-D) metal-organic framework materials [ML](n) [M = Ni, Co, Cd; L = N,N'-bis(4-picolinoyl)hydrazine] were obtained from hydrothermal reactions. The organic ligand L was formed through the in situ ring-opening hydrolysis reaction of 2,5-bis(4-pyridyl)-1,3,4-oxadiazole with the assistance of metal ions. Single-crystal X-ray diffraction studies reveal that complexes 1-3 adopt 6-connected 3-D networks of distorted alpha-Po topology, which are built from non-interpenetrated (4,4) grids cross-linked by zigzag chains. These isomorphic complexes are all of high thermal stability, but some other physical properties are quite different because of their different metal centers. Antiferromagnetic exchange was observed between Ni(II) centers of complex 1, while ferromagnetic for Co(II) centers of complex 2. Complex 3 exhibits strong fluorescence emission.

Comparison of MRI-based thrombolysis for patients with middle cerebral artery occlusion

OBJECTIVE: To investigate the outcomes of magnetic resonance imaging (MRI)-based thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute middle cerebral artery (MCA) occlusion in 3-6 hours. MATERIALS AND METHODS: MRI-selected patients (n=15) with acute ischemic stroke in MCA divided into two groups (

Treating ischaemic stroke with intravenous tPA beyond 4.5 hours under the guidance of a MRI DWI/T2WI mismatch was safe and effective.

Purpose: Clinical trials have provided evidence that treating patients with acute ischaemic stroke (AIS) beyond 4.5 hours was feasible. Among them using MRI diffusion-weighted imaging/fluid attenuation inversion response (DWI/FLAIR) mismatch to guide intravenous tissue plasminogen activator (tPA) was successful. Our study explored the outcome and safety of using DWI/T2-weighted imaging (T2WI) mismatch to guide intravenous tPA therapy for patients with AIS between 4.5 hours and 12 hours of onset. Method: This was a retrospective study. Records of 1462 AIS patients with the time of onset of <12 hours were reviewed. Those had MRI rapid sequence study and had hyperintense signal on DWI but normal T2WI and received intravenous tPA up to 12 hours of onset were included in the analysis. Their demographics, risk factors, post-tPA complications, National Institutes of Health Stroke Scale (NIHSS) scores and outcome were recorded and analyse. χ2 was used to compare the intergroup variables. SAS was used to perform statistical calculation. A p<0.05 was considered statistically significant. Results: Of 1462 identified, 601 (41%) patients were entered into the final analysis. Among them, 327 (54%) had intravenous tPA within 4.5 hours of onset and 274 (46%) were treated between 4.5-12 hours. After intravenous tPA, 426 cases (71%) had >4 pints of improvement on NIHSS score within 24 hours. Postintravenous tPA, 32 (5.32%) cases had haemorrhagic transformation. 26 (4.33%) were asymptomatic ICH and 4 (0.67%) died. At 90 days, 523 (87%) achieved a modified Rankin scale of 0-2. Conclusion: Using MRI DWI/T2WI mismatch to identify patients with AIS for intravenous tPA between 4.5 hours and 12 hours was safe and effective. The outcome was similar to those used DWI/PWI or DWI/FLAIR mismatch as the screening tool. However, obtaining DWI/T2WI was faster and avoided the need of contrast material.

MicroRNA expression profile of bronchioalveolar stem cells from mouse lung.

Increasing evidence has suggested that bronchioalveolar stem cell (BASC) is the progenitor cells of lung cancer stem cells. However, the mechanisms by which self-renewal of BSACs is controlled and how BASCs turn into cancer stem cells still remains to be unknown. In the present study, we successfully isolated bronchioalveolar stem cells (BASCs) from mouse lung using FACS. These BASCs were characterized by clonal growth, self-renewal and high capacity for differentiation, suggesting that these BASCs are indeed stem cells. We investigated the microRNA (miRNA) expression profile of these BASCs using miRNA array and quantitative RT-PCR. We discovered that BASCs possessed a unique miRNA profile, with altered expression of several microRNAs, such as miR-142-3p, miR-451, miR-106a, miR-142-5p, miR-15b, miR-20a, miR-106b, miR-25, miR-486, in BASCs compared to control cells. Our results suggest that microRNAs might play important roles in maintaining the self-renewal capacity of BASCs, and suggest the intriguing possibility that aberrant expression of microRNAs could involved in turning BASCs into lung cancer stem cells.

New optical supramolecular compound constructed from a polyoxometalate cluster and an organic substrate.

A new optical supramolecular compound constructed from a polyoxometalate cluster and an organic substrate [(H3O)(C12H10N3)2(PW12O40)] (1) has been synthesized via a hydrothermal reaction and has been structurally characterized by X-ray diffraction. The solid-state diffuse reflectance, IR, and photoluminescence spectra of the title compound indicate that there is an interaction between the alpha-PW12O40 and the organic substrate. The light-yellow title compound shows a certain second-order nonlinear optical response of I(2omega) = 2I(KDP)(2omega).

[Clinical treatment and prognosis for clear cell sarcoma: analysis of 19 cases].

OBJECTIVE: To explore the clinical features, prognosis, and optimal treatment strategy of clear cell sarcoma (CCS). METHODS: Nineteen patients, 12 males and 7 females, aged 30. 9, with histologically confirmed CCS, 3 with tumors > or =5 cm and 16 with tumors <5 cm, 5 tumors being located in the upper extremity, 2 in the hand, 6 in the lower extremity, 2 in the foot, 3 in the trunk, and 1 in the head, were hospitalized from March 1973 to March 2007. The primary tumors of all the cases were marginally excised before admission and 10 cases had local relapse at admission. Two presented local lymph node metastasis and 2 presented distant metastasis. Ten patients with tumor relapse underwent re-operation. Eight patients received chemotherapy, 8 radiotherapy and 1 combined chemotherapy and radiotherapy. The patients were followed up for 51.4 months (3-144 months). RESULTS: Tumor recurrence occurred in 1 of the 10 patients who received re-operation. 3 patients developed lymph node metastasis and 2 developed pulmonary metastasis. Of the 9 patients who did not undergo re-operation 7 developed lymph node metastasis, 6 developed pulmonary metastasis and 6 died. The overall 5-year survival rate was 75.2% and the 10-year survival rate was 37.5%. CONCLUSION: CCS is a rare and high grade soft tissue sarcoma with high incidence rates of local recurrence and metastasis, and poor prognosis. The role of chemotherapy and radiotherapy for CCS should be investigated further. The best choice after local recurrence is re-operation.

[Involvement of post-receptor signal transduction in alcohol addiction].

Alcohol abuse and addiction is not only a severe social problem, but also an important biological medical issue. Studies in neuropsychopharmacology and molecular neurobiology indicate that neurotransmitters and its receptors play important roles in alcohol abuse and addiction, and post-receptor signal transduction pathways, including cyclic adenosine 3', 5'-monophosphate (cAMP)-protein kinase A (PKA), phosphoinositide (PI), Ca2+ -calmodulin (CAM), phospholipase D (PLD) and tyrosine kinase Fyn signaling cascade. In this review, works on post-receptor signal transduction involved in alcohol addiction are systematically presented and summarized.