A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.

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.

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.

Objective The relationship between parasitic infections and cancer has become a research hotpot.Although reports of single intestinal protozoan infection in gastrointestinal cancer patients,co-infections are rare.To investigate co-infections of intestinal protozoa in gastrointestinal cancer patients.Methods The DNA of 195 fecal specimens was amplified using nested PCR and sequenced for the presence of Pentatrichomonas hominis,Giardia duodenalis,Cryptosporidium parvum,Blastocystis hominis,Dientamoeba fragilis,and Enterocytozoon bieneusi.Results An overall infection rate of 48.72％(95/195),with 23 cases(24.21％)co-infected with two parasites,three cases(3.16％)co-infected with three parasites.Additionally,67 cases(70.52％)were infected with one protozoa,including 56 cases with Pentatrichomonas hominis,one with Blastocystis hominis,nine with Cryptosporidium parvum,and one case with Dientamoeba fragilis.No infection with Enterocytozoon bieneusi was detected.Conclusion The results indicated a high rate of intestinal protozoan co-infection among gastrointestinal cancer patients.Through one-way ANOVA analysis,it was observed that cases of individual infection with P.hominis were significantly higher compared to those of co-infection with two or three types of protozoa containing P.hominis(P=0.0022)and cases of co-infection with three types of protozoa(P=0.0019).However,no significant difference in the infection rates was observed between two and three types of protozoa(P=0.2775),suggesting that cases of single infection with P.hominis were higher than cases of co-infection with two or more types of protozoa in gastrointestinal cancer patients.BLAST and single nucleotide polymorphism analysis revealed that gene sequences of different infected protozoa,except for a few with 100％homology to the GenBank reference sequence,exhibited varying degrees of base mutations,insertions,or loss at different loci.This study offers crucial insights for understanding the etiology,diagnosis,and prevention of gastrointestinal cancer.

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.

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*

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*

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.