Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.

Objective A simple,sensitive and rapid ultra high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for the determination of ertapenem in human plasma.Methods Using ertapenem-D4 as internal standard,the protein in plasma was precipitated with acetonitrile;chromatographic column:ACQUITY HSS T3(2.1 mm × 50.0 mm,1.8 μm);the mobile phase was 0.1％formic acid aqueous solution(containing 2 mmol·L-1 ammonium formate)-acetonitrile(0.1％formic acid),using a gradient elution;flow rate:0.4 mL·min-1,injection volume:1 μL,column temperature:45 ℃,the analysis time was 4.5 min,the scanning mode is positive ion selective reaction monitoring mode(SRM)with an electric spray ion source(ESI).The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effect,dilution effect and stability were investigated.Results Ertapenem had a good linearity within 0.5-80.0μg·mL-1,and the standard curve was y=4.25 × 10-1x-2.64× 10-2(r2=0.999 0),the lower limit of quantification was 0.5 μg·mL-1,the relative standard deviation within and between batches is 1.39％-4.15％.The extraction recovery rate was 58.36％-64.57％,and the relative standard deviation of dilution effect was 3.30％,and the matrix effect was 99.71％-103.23％.The relative standard deviation of room temperature,repeated freeze-thaw,4 ℃,and long-term stability are all less than 10％.Conclusion The method is sensitive,rapid and specific,which is suitable for clinical monitoring of Ertapenem.

Objective To analyze the literature related to diphenidol tablets poisoning,the characteristics of poisoning were summarized to provide reference for controlling the suicidal abuse risk of diphenidol tablets.Methods The global literature on suicide,overdose,poisoning,shock,and death related to difenidol published from January 1,2011 to December 31,2022 was analyzed,including gender,age,dosage,cardiac(blood)concentration,poisoning symptoms,etc.Results Young women were the majority of people with poisoning.The highest proportion of the age group is 11 to 30 years group.Patients who take medication doses greater than 3 000 mg may have a higher risk of death;patients with a heart(blood)concentration greater than 6 μg·mL-1 may have a higher risk of death.Malignant arrhythmia,consciousness disorders,coma,and apnea are common serious adverse events during poisoning.Conclusion It is recommended that the drug regulatory authorities should require the Listing permit holder of difenidol tablets to add the risk and symptoms of poisoning into the instructions.It is suggested that restricting individual consumers from purchasing large amounts of difenidol tablets in the short term.It is recommended that canceling the high-dose sales packaging of difenidol tablets.It is suggested that converting difenidol tablets into prescription drugs,even consider canceling the registration certificate of difenidol tablets.

OBJECTIVE: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. METHODS: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). CONCLUSION EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
Rats ; Animals ; Electroacupuncture ; Rats, Sprague-Dawley ; Serotonin ; Acupuncture Points ; Pain, Referred ; Calcitonin Gene-Related Peptide ; Signal Transduction ; Colitis/therapy* ; Indoles ; Sulfonamides

Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment. However, there are limitations, including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision, associated with gas therapy. In this study, we developed a series of photoactivatable nitric oxide (NO) donors NRh-R-NO (R = Me, Et, Bn, iPr, and Ph) based on an N-nitrosated upconversion luminescent rhodamine scaffold. Under the irradiation of 808 nm light, only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence (FUCL) signal at 740 nm, ascribed to lower N-N bond dissociation energy. We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy, including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation, the superoxide anion O₂^⋅- produced by the photodynamic therapy (PDT) effect of NRh-Ph, and highly toxic peroxynitrite anion (ONOO^‒) generated from the co-existence of NO and O₂^⋅-. After mild nano-modification, the nanogenerator (NRh-Ph-NO NPs) empowered with superior biocompatibility could target mitochondria. Under an 808 nm laser irradiation, NRh-Ph-NO NPs could induce NO/ROS to generate RNS, causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation, which further induced tumor immunogenic cell death (ICD). In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy, demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging. Collectively, this versatile strategy defines the targeted RNS-mediated cancer therapy.

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.