Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

AIM: To explore the relationship between retinal exudative changes in neonates and perinatal toxoplasmosis, others, rubella, cytomegalovirus, and herpes simplex virus(TORCH)infections, as well as the characteristics of TORCH infection in neonates with retinal exudative changes.METHODS: Retrospective study. A total of 612 neonates with retinal exudative changes detected during ophthalmic screening in our hospital from May 2019 to March 2023 were selected. TORCH tests were performed on these neonates, and the results were subjected to statistical analysis to determine the infection characteristics. The neonates with retinal exudative changes were grouped by sex and age, the characteristics of TORCH infection were analyzed, and the positive rates were compared.RESULTS: Among the 612 neonates with retinal exudative changes, the highest positive rate was observed for cytomegalovirus(CMV-IgG)(96.7%), followed by rubella virus(RV-IgG)(73.9%). Mixed infections with two or three viruses were also observed, with the highest positive rate for mixed infection of RV-IgG and CMV-IgG reaching 71.2%. There was no statistically significant difference in TORCH infection among neonates of different sex(P>0.05). However, there were statistically significant differences in RV-IgG and CMV-IgM infections with retinal exudative changes among neonates of different age groups(P<0.05).CONCLUSION: Perinatal TORCH infection may be an important factor causing retinal exudative changes in neonates. The differences in various infections are not related to sex but are related to different age groups.

The incidence of thrombosis-induced cardiovascular diseases is increasing worldwide and poses a serious threat to human health. Three factors, slow speed of blood flow, hypercoagulable blood and vascular damage, have been considered to be causes of thrombosis. Antithrombotic drugs have been classified into three categories based on the mechanism of thrombosis, including anticoagulants, platelet inhibitors and fibrinolytics. The coagulation and anticoagulation systems have drawn increasing attention because of the important role they play in the process of thrombosis. Novel compounds with anticoagulant activity are now emerging, alleviating to some extent some of the problems associated with the clinical use of early approved thrombotic drugs, such as high bleeding risk, slow onset of action and narrow therapeutic windows. In this review, we initially describe the mechanisms of coagulation as well as thrombosis. Meanwhile, a wide range of bioactive compounds and potential antithrombotic candidates reported in recent years have been summarized. In addition, the structure-activity relationship of certain compounds has been discussed, expecting to facilitate the development of molecules with anticoagulant biological activity for the treatment of thrombotic diseases.

Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.
Non-alcoholic Fatty Liver Disease ; Schisandra ; Insulin Resistance ; Lignans

Oxalicine B ( 1) is an α-pyrone meroterpenoid with a unique bispirocyclic ring system derived from Penicillium oxalicum. The biosynthetic pathway of 15-deoxyoxalicine B ( 4) was preliminarily reported in Penicillium canescens, however, the genetic base and biochemical characterization of tailoring reactions for oxalicine B ( 1) has remained enigmatic. In this study, we characterized three oxygenases from the metabolic pathway of oxalicine B ( 1), including a cytochrome P450 hydroxylase OxaL, a hydroxylating Fe(II)/α-KG-dependent dioxygenase OxaK, and a multifunctional cytochrome P450 OxaB. Intriguingly, OxaK can catalyze various multicyclic intermediates or shunt products of oxalicines with impressive substrate promiscuity. OxaB was further proven via biochemical assays to have the ability to convert 15-hydroxdecaturin A ( 3) to 1 with a spiro-lactone core skeleton through oxidative rearrangement. We also solved the mystery of OxaL that controls C-15 hydroxylation. Chemical investigation of the wild-type strain and deletants enabled us to identify 10 metabolites including three new compounds, and the isolated compounds displayed potent anti-influenza A virus bioactivities exhibiting IC₅₀ values in the range of 4.0-19.9 μmol/L. Our studies have allowed us to propose a late-stage biosynthetic pathway for oxalicine B ( 1) and create downstream derivatizations of oxalicines by employing enzymatic strategies.

Objective:To observe the incidence and risk factors of microcystic macular edema (MME) in patients with idiopathic macular epiretinal membrane (IMEM) preoperatively and postoperatively.Methods:A retrospective case series study. From January 2017 to May 2021, 72 eyes of 72 patients with IMEM in Eye Hospital of Wenzhou Medical University at Hangzhou were included. There were 18 male and 54 female. Average age was 64.8±7.8 years. Eyes were all monocular. All patients received the examination of best corrected visual acuity (BCVA) by standard logarithmic visual acuity chart, which was represented logarithmic of minimum angle of resolution (logMAR). Optical coherence tomography was used to measure central macular thickness (CMT). MME was defined as small, vertically bounded cystic space located outside the fovea in the inner layer of the retina. According to the presence or absence of MME before surgery, the affected eyes were divided into two groups: non-MME group (35 eyes) and MME group (37 eyes). The difference of logMAR BCVA and CMT was statistically significant between Group A and B ( t=3.117, 2.589; P=0.003, 0.012). All patients with IMEM were treated with 23G three-channels pars plana vitrectomy (PPV) with epiretinal membrane and inner limiting membrane (ILM) peeling. The two groups were further divided into four groups according to whether there was MME in the postoperative follow-up time. The group A1 was without MME before and after surgery, group A2 was without MME before surgery and with MME after surgery. The MME group was subdivided into the group with MME before surgery and without MME after surgery (group B1) and the group with MME before and after surgery (group B2). The mean follow-up time was 8.8±7.7 months. The same equipment and methods were used to exam the patients during the follow-up. Paired t test was used to compare the changes of MME, BCVA and CMT before and after surgery. The differences of CMT and BCVA among groups before and after surgery were compared by independent sample t test and one-way ANOVA. Logistic regression was used to analyze the influencing factors of MME before and after surgery, and multiple linear regression was used to analyze the influencing factors of postoperative BCVA. Results:There were 35 eyes in the non-MME group, 18 eyes (51.43%, 18/35) in the A1 group and 17 eyes (48.57%, 17/35) in the A2 group, respectively. There were 37 eyes in MME group, 6 eyes (16.22%, 6/37) in group B1 and 31 eyes (83.78%, 31/37) in group B2, respectively. At last follow-up, the logMAR BCVA was 0.10±0.12, 0.25±0.17, 0.09±0.11, 0.30±0.26 in group A1, A2, B1, and B2, respectively. Compared with the logMAR BCVA before surgery, the differences were statistically significant ( t=3.779, 4.253, 7.869, 6.668; P<0.01). There was significant difference in logMAR BCVA among the four groups ( F=4.460, P<0.01). There was a significant difference in logMAR BCVA between group A1 and group A2 ( t=-2.930, P=0.006). There was no significant difference between group B1 and group B2 ( t=-1.921, P=0.063). The CMT of group A1, A2, B1 and B2 were 371.83±73.24, 431.24±83.13, 407.00±28.07 and 425.19±70.97 μm, respectively. Compared with those before operation, the differences were statistically significant ( t=5.197, 2.465, 3.055, 6.078; P<0.05). There was no significant difference in CMT among the four groups ( F=2.597, P=0.059). Logistic regression analysis showed that pre-operation MME was correlated with pre-operation IMEM stage ( β=1.494, P=0.004). New MME after surgery was correlated with age ( β=0.153, P=0.013). Multiple linear regression analysis showed that postoperative visual acuity was significantly correlated with CMT before surgery and MME after surgery ( β=0.001, 0.134; P=0.015, 0.019). Conclusions:PPV combined with epiretinal membrane and ILM peeling surgery for IMEM can improve visual acuity and decrease CMT. MME regress or regenerate after surgery. Age is an independent predictor of the risk of newly formed MME after surgery.

Objective:To explore the positive rate of scanning laser ophthalmoscope in the retromode (RM-SLO) in different types of diabetic macular edema (DME), and to analyze its correlation with foveal thickness (CMT) and macular volume.Methods:From March to May 2021, 40 patients (65 eyes) were diagnosed as DME by fundus examination combined with optical coherence tomography (OCT) in Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. All eyes underwent best corrected visual acuity (BCVA), OCT and RM-SLO fundus imaging examinations, 47 eyes underwent fluorescein fundus angiography (FFA) examination. RM-SLO fundus imaging examinations were performed with Mirante SLO, including retro mode illumination deviated right (RMDR) and retro mode illumination deviated left (RMDL). If one or more of the RMDR and RMDL of the examined patient can identify macular edema, RM-SLO was considered to be able to identify macular edema. The macular volume at CMT and 6 mm from the fovea was measured by OCT software. DME were divided into 3 types based on OCT images: diffuse retinal thinkening (DRT) type; cystoid macular edema(CME) type; serous retinal detachment (SRD) type, focal leakage type, diffuse leakage type and diffuse cystic leakage type. The consistency of RMDR and RMDL in the diagnosis of DME in RM-SLO fundus imaging was evaluated, as well as their positive rate in different classifications of DME. The correlation between the detection of macular edema by RM-SLO and the DME type, CMT and foveal volume, and the correlation between BCVA and edema type, CMT and macular volume were analyzed.Results:Among 65 eyes, the positive rates of RMDR and RMDL fundus imaging to detect DME were 46 (70.77%, 46/65) and 48 (73.85%, 48/65), respectively. There was good consistency in identifying DME (Kappa value=0.770; P<0.001). The positive rates of RMDR and RMDL fundus imaging DRT, CME and SRD type of DME were 42.11% (8/19), 57.89% (11/19), 77.78% (28/36), 77.78% (28/36), 100.00% (10/10), 90.00% (9/10), respectively. In the FFA classification of them, the positive rates of focal leakage, diffuse leakage and diffuse cystic leakage were 68.75% (11/16), 62.50% (10/16), 68.00% (17/25), 76.00% (19/25), 100.00% (6/6), 100.00% (6/6), respectively. The results of Spearman correlation analysis showed that whether RM-SLO could identify DME was associated with CMT and OCT classification ( r=0.310, 0.365; P=0.120, 0.003); there was no correlation between FFA classification and macular volume ( r=0.113, 0.117; P=0.449, 0.352). BCVA was correlated with CMT and macular volume ( r=0.307, 0.269; P=0.013, 0.030), however, there was no significant correlation with OCT type, angiographic type ( r=0.051, 0.175; P=0.684, 0.240). Conclusion:The diagnostic agreement of DME are good between RMDR, RMDL of RM-SLO image. DME of DRT type and patients with smaller CMT in OCT are difficult to identified by RM-SLO fundus imaging.

OBJECTIVE: To investigate the changes in autophagy of mesenchymal stem cells (MSCs) from patients with ankylosing spondylitis and explore the mechanism for decreased autophagy in ASMSCs. METHODS: MSCs collected from 14 patients with AS (ASMSCs) and from 15 healthy donors (HDMSCs) were cultured in the absence or presence of 25 ng/mL TNF-α for 6 h. Autophagy of the cells was determined by immunofluorescence staining of GFP-LC3B, and the results were confirmed by detecting the protein expressions of autophagy markers LC3 II/LC3 I and P62. The mRNA expressions of the related genes were detected using qRT-PCR, and the protein expressions of the autophagy markers and signaling pathway-related molecules were determined with Western blotting. TG100713 was used to block the PI3K/AKT/mTOR signal pathway, and its effect on autophagy of ASMSCs was evaluated. RESULTS: ASMSCs showed significantly weaker GFP-LC3B puncta staining and lower protein expression levels of LC3 II/LC3 I but higher levels of P62 protein (P < 0.05), indicating a decreased autophagy capacity as compared with HDMSCs. TNF-α-induced ASMSCs showed significantly higher protein expressions of p-PI3K/ PI3K, p-AKT/AKT and p-mTOR/mTOR than HDMSCs (P < 0.05), suggesting hyperactivation of the PI3K/AKT/mTOR signaling pathway in ASMSCs. Blocking PI3K/AKT/mTOR signaling with TG100713 eliminated the difference in TNF-α-induced autophagy between HDMSCs and ASMSCs. CONCLUSION In patients with AS, hyperactivation of the PI3K/AKT/mTOR signaling pathway results in decreased autophagy of the MSCs and potentially contributes to chronic inflammation.
Autophagy ; Humans ; Mesenchymal Stem Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Spondylitis, Ankylosing ; TOR Serine-Threonine Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

The accelerometry(AMG) muscle relaxant monitor is the most widely used quantitative muscle relaxant monitor to assess the degree of neuromuscular at present. In this study, the ulnar nerve was stimulated by using train of four stimulation(TOF) mode of the AMG muscle relaxant monitor, and the movement of the adductor pollicis muscle was monitored. In this way, the distribution range of key parameters (acceleration peak value, response time, and TOF ratio) of the adductor pollicis muscle during the use of muscle relaxant in clinical practice is analyzed and will provide a practical basis for the development and improvement of the muscle relaxant monitor.
Electric Stimulation ; Muscle, Skeletal ; Neuromuscular Blockade ; Neuromuscular Nondepolarizing Agents ; Ulnar Nerve/physiology*

Applying the effective teaching theory to the small-class teaching of pharmacology can improve the flexibility of small-class teaching mode under the guidance of the concept of effective teaching and high efficiency. The course chapters were randomly selected for traditional teaching mode or small-class teaching mode based on effective teaching theory in the same class. Practice has proved that the small-class teaching based on AO-AMFM can enhance student analysis and make careful smart objective and teaching frame work before class, and can also reach prompt activation, multi-learning, effective feedback and multi-summary, which can significantly improve students' learning enthusiasm and learning efficiency.