AIM: To design a simple and effective auxiliary device for detection of the compound action poten-tial (CAP) and the force on the isolated sciatic nerve and gastrocnemius in toads, and to investigate its practicability. METHODS: A simple “L” shape device (L tube), which was composed of a nerve chamber and an organ bath, was made for fixing the isolated sciatic nerve and gastrocnemius.After fixing, the sciatic CAP and the gastrocnemius force were detected by BL-420S data acquisition and analysis system.The specimens were radomly divided into control group, and the lidocaine nerve and muscle groups.The sciatic nerve or gastrocnemius of each lidocaine group was firstly treated with the corresponding concentration of lidocaine, and then washed out with Ringer’s solution, and its reversible anesthetic action on nerve conduction and muscle force was analyzed to verify the practicability of the L tube device.RESULTS: The CAP and the force of the sciatic-gastrocnemius specimens were detected concurrently by fixing the specimens in the L tube, and the liquid in the nerve chamber and organ bath was changed easily.Compared with the control, lidocaine at 0.05 and 0.2 g/L significantly increased the sciatic threshold stimulus voltage and maximal stimulus voltage (P <0.05), prolonged the absolute refractory period (P <0.01), and slowed down the conduction velocity (P <0.01).Lidocaine at 1 g/L complete-
ly blocked the sciatic conduction.The rest tension of the gastrocnemius was increased, and the maximal twitch force was decreased significantly by 1 g/L lidocaine (P <0.01), but the threshold and maximal stimulus voltage did not show statis-tic difference.The parameters of the sicatic nerve and gastrocnemius completely or partially recovered to the control level after washing out.CONCLUSION: As an auxiliary device, L tube makes the detection of CAP and force on the isolated sciatic nerve and gastrocnemius in toads more conveniently.

OBJECTIVETo explore whether strontium ranelate (Sr) promotes osteoblast lineage differentiation of rat bone mesenchymal stem cells (BMSCs) through the bone morphogenetic protein-2 (BMP-2)/Smad signaling pathway.

METHODSCultured rat BMSCs were exposed to different concentrations of Sr, noggin (an inhibitor of BMP-2) or Smad1 siRNA. The activity of alkaline phosphatase (ALP) in the exposed cells was detected by colorimetry, and the formation of mineralized nodules was observed with alizarin red staining. The expressions of phosphorylated (p) Smad1/5/8 and Runt-related transcription factor 2 (Runx2) in the cells were detected by Western blotting.

RESULTSExposure to Sr at 0.1 to 10 mmol/L for 1 h markedly increased the expression of p-Smad1/5/8 in the BMSCs, and the increment was the most obvious following 1 mmol/L Sr exposure. Preconditioning with 100 ng/ml noggin for 2 h inhibited Sr-induced up-regulation of p-Smad1/5/8 expressions. Exposure of the cells to 0.1 to 5 mmol/L Sr for 6 h significantly enhanced Runx2 expression, and the peak enhancement occurred following 1 mmol/L Sr exposure. Transfection of the BMSCs with Smad1 siRNA decreased the basal level of Smad1/5/8 protein expression, and also inhibited Sr-induced up-regulation of p-Smad1/5/8 and Runx2 expressions as well as Sr-induced enhancement of ALP activity and formation of mineralized nodules.

CONCLUSIONThe BMP-2/Smad pathway is involved in Sr-induced osteoblast differentiation of rat BMSCs.

Alkaline Phosphatase ; metabolism ; Animals ; Bone Marrow Cells ; cytology ; Bone Morphogenetic Protein 2 ; metabolism ; Cell Differentiation ; drug effects ; Cells, Cultured ; Mesenchymal Stromal Cells ; cytology ; Osteogenesis ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad1 Protein ; metabolism ; Strontium ; pharmacology ; Thiophenes ; pharmacology

AIM: To investigate the effects of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow stem cells on treatment of the myocardial infarction in experimental rats. METHODS: Three hours after injected with isoprenaline(ISO) interaperitoneally to develop acute ischemic model, rats' bone marrow stem cells were mobilized by G-CSF and migrated to the site of myocardial infarction. The hearts were harvested from 24 hours to 2 weeks after administration of ISO for histopathological examination. RESULTS: 24 hours after administration of ISO , myocardial infarct zones scattered in the pallium of the control group ,there were a large amoumt of inflammatory cells infiltration around the infarct zones and majority of them were neutrophils. The infarction in the G-CSF treatment group was milder, majority of the infiltrative cells were monocytoid; 48 hours after administration of ISO, infarct zones expanded greatly in control group, while that of the G-CSF treatment group increased just mildly; 2 weeks after administration of ISO, there was no significant scar in the G-CSF treatment group. We also found the regeneration of myocytes in the pallium. CONCLUSION: G-CSF treatment protected the ischemic myocardium and it may be used to treat the acute myocardial infarction.

AIM:To explore the inhibitory effects of tumor associated mitochondrial protein 12 (TAMP12) on tumor cell apoptosis. METHODS: (1) A retrovirus expression vector was recombinated and transfected into the packaging cell line PA317. The virus particles were obtained to infect the target cell line HepG2 low expressing of TAMP12. The expression of TAMP12 mRNA was detected by RT-PCR. The subcellular localization and quantification of TAMP12 protein labeled with double fluorescein were observed under confocal laser scanning microscope (CLSM). (2) Hoechst33258 staining and flow cytometry (FACS) were used to analysis the apoptosis of HepG2 cells treated with 5-fluorouracil (5-FU). RESULTS: (1) The CLSM observation showed that TAMP12 protein was mainly expressed in mitochondria of HepG2 cells. The expressions of TAMP12 gene and protein were stable and high in transfected HepG2 cells. (2) Upon treatment with 5-FU, the transfected HepG2 cells showed a fairly integrated nucelus while the control HepG2 cells exhibited chromatin condensation, marginalization and karyorhexix. Moreover, the apoptosis rate of transfeced HepG2 cells was significantly lower than that in control HepG2 cells (P

Objective To study the effect and safety of ticagrelor on platelet in ＞75 years old patients undergoing PCI.Methods One hundred and twenty ＞75 years old patients with acute coronary syndrome undergoing PCI were randomly divided into observation group treated with aspirin+ticagrelor (n =60) and control group treated with aspirin+ clopidogrel (n =60).They were followed up for 1 year after PCI.The major adverse cardiovascular events (MACE),bleeding events,drug-related side effects and all-cause mortality were compared between the two groups.Results No instent thrombosis occurred in any patients,myocardial infarction occurred in 2 patients,angina pectoris occurred in 5 patients and 3 patients died in observation group after 1 year of PCI.Instent thrombosis occurred in 4 patients,myocardial infarction occurred in 3 patients,angina pectoris occurred in 6 patients,and 4 patients died in control group after 1 year of PCI.The incidence of instent thrombosis was significantly lower while that of mild dyspnea was significantly higher in observation group than in control group (0％ vs 6.7％,10.0％ vs 0％,P＜0.05).Conclusion Ticagrelor can effectively prevent instent thrombosis and does not increase the risk of bleeding in ＞75 years old patients after PCI.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of notochordal tumors.Methods:The clinical, radiologic and pathologic data of 48 notochordal tumors were collected from 2008 to 2019 at Shanghai Jiaotong University Sixth People′s Hospital. Expression of cytokertin, S-100 protein, vimentin, brachyury and INI1 was detected by immunohistochemistry. The pathologic differential diagnoses and biologic behavior of various types of notochordal tumors were analyzed using the new standard in the 5th edition of WHO tumor classification.Results:Four cases of benign notochordal cell tumor were confined to vertebral body. Histopathologically, they lacked lobular architecture and extracellular myxoid matrix. The tumor cells were vacuolated and had centrally or peripherally located round to oval nuclei, with small nucleoli, without atypia, mimicking mature adipocytes. No mitotic figures were seen. Two cases of poorly differentiated chordoma, from patients aged 12 years and 21 years respectively, were located in cervical vertebra, and were composed of cohesive sheets or nests of epithelioid cells, with focal rhabdoid morphology. There was relatively abundant eosinophilic cytoplasm and scattered cytoplasmic vacuoles. The moderately pleomorphic nuclei were round to ovoid with vesicular chromatin and mitotic figures could be seen. Extracellular myxoid stroma was observed focally. Forty cases of conventional chordoma and two cases of extra-axis chordoma had similar histologic features. All 48 cases expressed cytokeretin, 45 cases expressed brachyury, and two poorly differentiated tumors showed loss of INI1/SMARCB1.Conclusions:There are four subtypes of chordomas: conventional, dedifferentiated, poorly differentiated and extra-axis. Chondroid chordoma is no longer thought to be a distinct entity. Each type has its unique clinicopathological characteristics. Brachyury is highly specific and sensitive for the diagnosis of various notochordal tumors. Poorly differentiated chordoma shows distinct clinicopathological features, including young age and loss of immunohistochemical expression of INI1/SMARCB1, and its diagnosis requires the combined detection of brachyury and INI1/SMARCB1.

Objective To report 2 rare cases of benign notochordal cell tumor ( BNCT) , according to WHO classification of tumors of soft tissue and bone (4th edition).Their radiologic and clincopathologic features and differential diagnosis were investigated.Methods Two cases of BNCT were studied by retrospective review of the clinical , radiologic, pathologic and immunophenotypical findings.Related literatures were reviewed at the same time.Results Case 1 was a 53-year-old man, and case 2 was a 61-year-old woman.Radiographically , both patients presented with abnormal imaging findings in the fifth cervical vertebral body with the lesions located within the bone but without extra osseous mass .Histopathologically , the lesions lacked lobular architecture and extracellular myxoid matrix.The tumor cells were vacuolated and had centrally or peripherally placed round or oval nuclei with small nucleoli , mimicking mature adipocytes.No cytological atypia or mitotic figures were seen.The affected bone trabeculae were sclerotic and islands of bone marrow were often entrapped within the tumor.Conclusions Although sharing similar anatomic distribution and immunophenotype to those of chordoma , BNCT has distinct radiologic and pathologic features and different treatment and prognosis.The differential diagnosis between BNCT and chordoma requires detailed clinical , radiologic and histopathologic evaluations.

Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.

OBJECTIVETo study the clinicopathologic features and differential diagnosis of giant cell-rich osteosarcoma (GCRO) and giant cell tumor of bone (GCT).

METHODSThe clinical, radiologic, pathologic and immunohistochemical features of 18 cases of GCRO and 118 cases of GCT were evaluated.

RESULTSThe mean age of patients with GCRO was 24.6 years. Fifteen of the 18 cases arose in the metaphysis of long bones. GCRO presented as a large poorly-defined mixed lytic and blastic mass, associated with cortical destruction and formation of large soft tissue component. Histologically, GCRO was characterized by a predominance of numerous osteoclast-like giant cells admixed with scanty osteoid which was formed by neoplastic cells in different levels of anaplasia and pleomorphism. In the 118 cases of GCT studied, the mean age of patients was 34.5 years. Most of them (108 cases) arose in the epiphyseal region of long bones. They usually presented as expansile eccentric and osteolytic lesions. Invasive GCT displayed local cortical destruction. Histologic examination of GCT revealed the presence of large number of osteoclast-like giant cells and mononuclear stromal cells. The mononuclear stromal cells possessed poorly defined cytoplasm, showed little cytological atypia and did not carry atypical mitotic figures. They were positive for p63 (83.9%, 99/118). Reactive bone could be observed at the periphery.

CONCLUSIONSGCRO represents a special form of osteosarcoma which shows overlapping clinicopathologic features with invasive GCT. The presence of nuclear atypia, atypical mitoses and osteoid matrix produced directly by neoplastic cells are more in favor of GCRO. These features however may not be demonstrated in full in limited small biopsy samples. It is thus important to analyze all clinical, radiologic and pathologic features before a definitive diagnosis is made.

Adult ; Bone Neoplasms ; diagnosis ; pathology ; Diagnosis, Differential ; Giant Cell Tumor of Bone ; diagnosis ; pathology ; Giant Cells ; pathology ; Humans ; Osteosarcoma ; diagnosis ; pathology