Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7 135 reports of tizanidine ADE were obtained,including 1 732 patients,1 304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1 732 patients,the number of ADE cases of female was 2.37 times that in male(1 057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03％).The highest proportion(32.79％)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38％).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.

BACKGROUND: How to locate pulmonary ground-glass nodules in thoracoscopic surgery is an important clinical topic in minimally invasive thoracic surgery. There is no unified localization method at present. This study intends to investigate the accuracy and security of body surface theodolitic puncture localization method in video-assisted thoracoscopic surgery for pulmonary ground-glass nodules. METHODS: The clinical data of 41 patients from August 2018 to December 2019 were analyzed retrospectively, including 28 males and 13 females. After anesthesia, the patient was located by body surface theodolitic puncture, and then partial lobectomy was performed under video-assisted thoracoscopy. The distance from the nodule to the marked suture and the distance from the nodule to the incisal margin were measured, and the accuracy of localization, the rate of complication and the success rate of surgical resection were calculated. RESULTS: A total of 51 nodules in 41 patients were located by body surface theodolitic puncture localization method. The accuracy rate was 96.1%, and the average location time was 8.3 min. Puncture bleeding occurred in 5 cases (12.2%), all of which were successfully stopped by video-assisted thoracoscopy, and there were no other complications. All patients underwent thoracoscopic partial lobectomy, including 33 cases of anatomical segmentectomy and 8 cases of wedge lobectomy. All the patients in operation process smoothly. The distance between nodule and incisal margin was measured, and all specimens were more than 2 cm, reaching a safe distance. The success rate of surgical resection was 100.0%. CONCLUSIONS In video-assisted thoracoscopic surgery for ground glass nodules of lung, the body surface theodolitic puncture localization method can be accurate, safe and simple.

Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome profiles of single light-stimulated neuron in V1 remain unknown. In our study, in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as light-sensitive (LS) or non-light-sensitive (NS) by single-cell light-evoked calcium evaluation and action potential spiking. The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing. Moreover, the three-dimensional (3-D) morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings. Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation, such as Rtn4r and Rgs7, and genes involved in membrane transport, such as Na/K ATPase and NMDA-type glutamatergic receptors, preferentially responded to light stimulation. Furthermore, an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice. In conclusion, our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.

Objective To study the clinical value of anti-oxidative stress biomarkers for diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.Methods A total of 72 advanced-aged patients with in-stent restenosis and in-stent reocclusion after coronary stent implantation were successively recruited in this retrospective study from February 2010 to November 2017.Changes in serum superoxide dismutase 3(SOD3),nitric oxide(NO),endothelial cell nitric oxide synthase(eNOS)and malondialdehyde(MDA)levels were measured.Results Serum 1evels of SOD3,NO and eNOS decreased and serum MDA levels were elevated in advanced-aged patients with in-stent restenosis.There were significant differences in serum levels of SOD3,NO,eNOS and MDA between the advanced-aged patients without in-stent restenosis and the advanced-aged patients with multivessel in-stent restenosis or reocclusion[(20.0±3.2) × 103U/L vs.(10.9±3.9) ×103U/L,(61.2±14.2)μmol/L vs.(28.3±17.2)μmol/L,(75.9±24.7)ng/L vs.(33.0±119.6)ng/L,(2.2±1.4)nmol/L vs.(11.7±3.1)nmol/L,respectively,P＜0.01].Patients with 50-69％ restenosis had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with 100％ restenosis[(21.3 ± 2.9) × 103 U/L vs.(10.3 ± 4.0) × 103 U/L,(59.7 ± 16.7) μmol/L vs.(38.3 ±16.3)μmol/L,(74.5±21.1)ng/L vs.(41.9±26.8)ng/L,(2.6±3.9 nmol/L)vs.(10.1±3.1)nmol/L,respectively,P ＜ 0.01].Patients with left ventricular ejection fraction (LVEF) ≥ 55 ％ had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with LVEF＜30％ [(21.0±4.1) × 103 U/L vs.(5.3±1.9) × 103 U/L,(60.1 ± 14.2)μmol/L vs.(29.0± 13.2)μmol/L,(74.7±25.1)ng/L vs.(39.3 ± 20.3) ng/L,(2.3 ± 1.5) nmol/L vs.(10.0 ± 3.9) nmol/L,respectively,P ＜0.01].Serum levels of SOD3,NO and eNOS were higher and MDA levels were lower in patients with New York Heart Association(NYHA)Class Ⅰ than in patients with NYHA Class Ⅳ[(22.1±3.5)×103U/L vs.(9.7±2.9) × 103 U/L,(62.9± 13.9)μmol/L vs.(24.9± 13.3)μmol/L,(76.7±26.7) ng/L vs.(41.9±21.5)ng/L,(2.7± 1.9)nmol/L vs.(8.7±3.8)nmol/L,respectively,P＜0.01].Conclusions Serum level changes of anti-oxidative stress biomarkers such as SOD3,NO and eNOS may have clinical value in diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.

OBJECTIVE： To investigate the effects of adiponectin （APN） on the expression of myocardial AMPK in myocardial insulin resistance （IR） model dogs during cardiopulmonary bypass （CPB）. METHODS： Totally 24 dogs were randomly divided into control group， model group， APN group （36 μg/kg）， AMPK inhibition group （APN 36 μg/kg+AMPK inhibitor compound C 0.5 mg/kg）， with 6 dogs in each group. All dogs underwent CPB； except for control group without medicine， CPB myocardial IR model were established in other groups， and perfused with St.Thomas cardiac cardioplegia lipid no medicine or containing relevant drugs after main artery block. Coronary sinus blood and carotid artery blood samples were collected before bypass and after 15， 90 min reperfusion following 60 min myocardial ischemia. Left ventricular apical tissue was taken， and the uptake rate of myocardial glucose and insulin resistance index （IRI） were determined and calculated； the changes of myocardial injury indexes （cTnT concentration） and cardiac function indexes （LVSP， +dp/dtmax） were monitored. The level of p-AMPK was detected. RESULTS： There was no statistical significance in above indexes of dogs before bypass （P＞0.05）. Compared with control group， the rate of myocardial glucose uptake， the levels of LVSP， +dp/dtmax and p-AMPK in model group were decreased significantly after 15， 90 min reperfusion （P＜0.05）， and the concentrations of IRI and cTnT were increased significantly （P＜0.05）. Compared with model group， the rate of myocardial glucose uptake， LVSP， +dp/dtmax and p-AMPK were increased significantly in APN group and AMPK inhibitor group （P＜0.05）， while the concentrations of IRI and cTnT were decreased significantly （P＜0.05）； moreover， the effect of APN group was better than that of AMPK inhibitor group （P＜0.05）. CONCLUSIONS： APN can promote myocardial glucose uptake and metabolism， and contribute the recovery of cardiac function， the mechanism of which may be associated with increasing the activity of AMPK.

Objective To investigate risk factors for in-stent restenosis and reocclusion after coronary stent implantation in aged patients.Methods 131 patients diagnosed with chronic total occlusion and old myocardial infarction due to coronary stenosis were recruited in this retrospective study from Mar 2004 to May 2015.Patients were divided into 50 to 59 years old group (n=51),60 to 69 years old group (n=43),and 70 to 80 years old group (n=37) to study coronary lesion characteristics.In-stent restenosis and reocclusion were detected at 6,12,18,and 24 months after coronary stent implantation.Results Before coronary stent implantation,the incidence rate of type 2 diabetes was significantly increased with three increasing age groups:9.8％ at ages 50-59 group (n=5),18.6％ at ages 60-69 group (n=8),and 27.0％ at ages 70-80 group (n=10) (all-P＜0.01).The incidence rates of multiple coronary artery disease,long coronary lesions (＞20 mm),eccentric coronary lesions,serious angle of coronary lesions,irregular coronary lesions,proximal coronary curvature,moderate to severe calcified coronary lesions,coronary restenosis (90％-99％ or 100％),and complex bifurcation lesions were significantly elevated with three increasing age groups (P ＜0.01 or P ＜0.05).The ratios of patients with in-stent restenosis at 24 months after coronary stent implantation were significantly elevated with three increasing age groups:at 9.8％ (n=5),18.6％ (n=8),and 27.0％(n=10) for 90％ 99％ restenosis sub-group,and at 5.9％ (n=3),14.0％ (n=6) and 24.3％ (n=9) for 100％ restenosis sub-group,respectively (all P＜0.05 or P＜0.01)Conclusions Type 2 diabetes is an independent risk factor for complex coronary lesions in aged patients Complex coronary lesions,three or more stents,and long coronary stents may lead to ir-stent restenosis and reocclusion after coronary stent implantation in aged patients.

The main purpose of the present study was to investigate the cell behaviors of rat primary osteoblast cells on extracellular matrix (ECM) protein micropatterns. For this purpose, a series of fibronectin micropatterns with different shapes and varying dimensions were created on polystyrene (PS) surfaces by microcontact printing. The results of confocal laser scanning microscopy (CLSM) images indicated that excellent micropatterns were successfully obtained. These protein patterns were stable during the cell culture. The cell experiments suggested that the osteoblast cells preferentially attached onto protein-functionalized areas and displayed different cell shape and spreading behavior on different protein micropatterns. The protein micropatterns can significantly influence the cell adhesion, spreading, alignment and orientation and so on. Therefore, this work can be used to modify biomaterial surfaces, especially that of bone-implant biomaterials, to effectively control cell behavior. It further contributes to clarify the interfacial biological behaviors between biomaterials and osteoblast and can provide the cues for development of bone implantable materials which is able to modulate osteoblast cell growth behavior.
Animals ; Animals, Newborn ; Cell Adhesion ; drug effects ; Cell Movement ; drug effects ; Cells, Cultured ; Extracellular Matrix Proteins ; pharmacology ; Osteoblasts ; cytology ; Rats ; Surface Properties

One group of Bcl-2 protein family, which shares only the BH3 domain (BH3-only), is critically involved in the regulation of programmed cell death. Herein we demonstrated a novel human BH3-only protein (designated as Bop) which could induce apoptosis in a BH3 domain-dependent manner. Further analysis indicated that Bop mainly localized to mitochondria and used its BH3 domain to contact the loop regions of voltage dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane. In addition, purified Bop protein induced the loss of mitochondrial transmembrane potential (Δψm) and the release of cytochrome c. Furthermore, Bop used its BH3 domain to contact pro-survival Bcl-2 family members (Bcl-2, Bcl-X(L), Mcl-1, A1 and Bcl-w), which could inhibit Bop-induced apoptosis. Bop would be constrained by pro-survival Bcl-2 proteins in resting cells, because Bop became released from phosphorylated Bcl-2 induced by microtubule-interfering agent like vincristine (VCR). Indeed, knockdown experiments indicated that Bop was partially required for VCR induced cell death. Finally, Bop might need to function through Bak and Bax, likely by releasing Bak from Bcl-X(L) sequestration. In conclusion, Bop may be a novel BH3-only factor that can engage with the regulatory network of Bcl-2 family members to process intrinsic apoptotic signaling.
Amino Acid Sequence ; Animals ; Apoptosis ; Cell Line ; Cell Survival ; Humans ; Mice ; Mitochondria ; metabolism ; Mitochondrial Membranes ; metabolism ; Molecular Sequence Data ; Protein Structure, Tertiary ; Protein Transport ; Proto-Oncogene Proteins c-bcl-2 ; chemistry ; metabolism ; Signal Transduction ; Time Factors ; Voltage-Dependent Anion Channel 1 ; metabolism ; bcl-2 Homologous Antagonist-Killer Protein ; metabolism ; bcl-2-Associated X Protein ; metabolism

In-stent restenosis is the major problem in clinical application of coronary stent. Drug-eluting stent became a landmark in the treatment of coronary disease. However, thrombosis is still a problem of drug-eluting stent. There has been clinical report indicating that thrombosis sometimes is induced by drug-eluting stent implantation in late stage. Curcumin could be used for drug-eluting stent due to its antithrombogenity and antiproliferative properties. In this paper, three weight percent curcumin-loaded films (3wt%, 5wt%, 8wt%) were prepared using a biodegradable polymer (poly (lactic acid-co-glycol acid), PLGA) as the carrier of curcumin. The component of curcumin-loaded film was analyzed by Fourier transform infrared spectroscopy (FTIR), and the major peaks of curcumin and PLGA were both observed in the composite film. The result of in vitro platelet adhesion test shows that the number of adhered platelet reduces, and few aggregated and activated platelets are observed. For all composite films, activated partial thromboplastin time (APTT) increases. The results indicate that the curcumin-loaded films have better anticoagulative effect when compared with PLGA. In addition, all anticoagulation tests indicate "the higher the drug content in the film, the better the anticoagulative effect".
Coated Materials, Biocompatible ; pharmacology ; Coronary Restenosis ; prevention & control ; Curcumin ; pharmacology ; Drug-Eluting Stents ; Humans ; Lactic Acid ; pharmacology ; Platelet Adhesiveness ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Polyglycolic Acid ; pharmacology ; Polymers

In-stent restenosis is the major problem of percutaneous coronary interventions. Drug-eluting stent became a landmark in the treatment of coronary disease. Curcumin could be used for drug-eluting stent due to its antithrombogenity and antiproliferative properties. In this paper, 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were performed to decide the optimal concentration of curcumin for inhibiting the proliferation of vascular smooth muscle cells (VSMC). The result disclosed that more than 80% of VSMC were inhibited when the concentration of curcumin ranged from 2.5 microg/ml to 10 microg/ml (P < 0.05, compared to ethanol). Three weight percent curcumin-loaded films (3wt%, 5wt%, 8wt%) were prepared using a biodegradable polymer (poly (lactic acid-co-glycol acid), PLGA) as the carrier of curcumin. The release of lactate dehydrogenase (LDH) was used to evaluate the immediate toxicity of the curcumin-loaded PLGA films, and the three concentration curcumin-loaded films were revealed to be of no acute toxicity to the smooth muscle cells. The results of Alamar Blue test indicated that the curcumin-loaded films had better antiproliferation effect than did the 316 stainless steel (SS). Therefore, these films may be used for stent coating to inhibit the in-stent restenosis induced by VSMC proliferation.
Angioplasty, Balloon, Coronary ; Animals ; Carotid Arteries ; cytology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Coated Materials, Biocompatible ; pharmacology ; Coronary Restenosis ; prevention & control ; Curcumin ; pharmacology ; Drug-Eluting Stents ; Lactic Acid ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; Polyglycolic Acid ; pharmacology ; Rats