OBJECTIVE To prepare reactive oxygen species （ROS）-responsive methotrexate （MTX）-modified paclitaxel （PTX）/icariin （ICA） micelles （MTX-oxi-Ms@PTX/ICA）， and perform technology optimization and in vitro anti-tumor effect evaluation. METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test. The micelles were prepared by thin film hydration method， and their technology was optimized by response surface methodology. The fundamental characteristics of the micelles prepared by the optimal technology were evaluated. The micelles’ cytotoxicity， targeting ability to renal carcinoma RENCA cells of mice， and their inhibitory effects on invasion and migration were assessed. RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L. The optimal technology of MTX-oxi-Ms@PTX/ ICA was determined to include 80 mg Soluplus®， Soluplus® and TPGS1000 mass ratio of 4∶1 （mg/mg）， 2 mg DSPE-PEG2000-TK- PEG5000， 2 mg DSPE-PEG2000-MTX， 1 mg PTX， and 1.5 mg ICA， with a hydration temperature of 35 ℃ and a formulation volume of 5 mL. Under the optimal conditions， average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi- Ms@PTX/ICA reached 92.75%， the critical micelle concentration （CMC） was 0.007 9 mg/mL， the particle size was （62.09±1.68） nm， the polydispersity index （PDI） was 0.046±0.032， and the Zeta potential was （－2.47±0.15） mV. Within 30 days of placement， there was no significant change E-mail：yingqiang_1126@163.com in particle size and polydispersity index of micelle. In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments. The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was （5.170±0.036） μmol/L. In vitro cellular uptake experiments indicated that compared with unmodified micelles， MTX modified micelles had stronger targeting effects on cancer cells， and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells （P＜0.05）. CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared， which exhibit high encapsulation efficiency， low critical micelle concentration， and good stability. These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.

Glaucoma is a group of optic nerve disorders characterized by progressive optic nerve atrophy and visual field defects, which can lead to irreversible blindness. Early diagnosis of glaucoma is essential for preventing visual loss. However, due to the absence of obvious early symptoms, the diagnosis of glaucoma remains challenging. Visual electrophysiological examinations, an objective approach for evaluating visual function, have the potential to be used in the early diagnosis of glaucoma. This review integrates the latest publications to introduce visual electrophysiological examination techniques, including electroretinography(ERG)and visual evoked potential(VEP). It also explores the mechanisms underlying these techniques and their application value in the early diagnosis of glaucoma. In addition, this review summarizes the advantages, limitations, and applicable scenarios of different visual electrophysiological techniques. Finally, the review provides an outlook on the development prospects of visual electrophysiological techniques in the early diagnosis of glaucoma. The findings of this review can assist clinicians in selecting appropriate diagnostic methods, promote the innovation and development of early visual electrophysiological diagnostic techniques for glaucoma, and contribute to reducing the risk of blindness caused by glaucoma.

Purpose: To evaluate the incidence and identify the risk factors for radiotherapy-induced oral mucositis among patients with nasopharyngeal carcinoma. Methods: A meta-analysis was conducted. Eight electronic databases (Medline, Embase, Cochrane Library, CINAHL Plus with Full Text, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journals Database) were systematically searched from inception to 4 March 2023 for relevant studies. Study selection and data extraction were conducted by two independent authors. The Newcastle‒Ottawa scale was used for quality assessment among the included studies. Data synthesis and analyses were performed in R software package version 4.1.3 and Review Manager Software 5.4. The pooled incidence was calculated using proportions with 95% confidence intervals (CIs), and the risk factors were evaluated using the odds ratio (OR) with 95% CIs. Sensitivity analysis and predesigned subgroup analyses were also conducted. Results: A total of 22 studies published from 2005 to 2023 were included. The results of the meta-analysis showed that the incidence of radiotherapy-induced oral mucositis was 99.0% among nasopharyngeal carcinoma patients, and the incidence of severe radiotherapy-induced oral mucositis was 52.0%. Poor oral hygiene, overweight before radiotherapy, oral pH < 7.0, the use of oral mucosal protective agents, smoking, drinking, combined chemotherapy, and the use of antibiotics at early treatment stage are risk factors for severe radiotherapy-induced oral mucositis. Sensitivity analysis and subgroup analyses also revealed that our results are stable and reliable. Conclusions Almost all patients with nasopharyngeal carcinoma have suffered from radiotherapy-induced oral mucositis, and more than half of patients have experienced severe oral mucositis. Facilitating oral health might be the key focus of reducing the incidence and severity of radiotherapy-induced oral mucositis among nasopharyngeal carcinoma patients.Registration numberCRD42022322035.

Objective:To observe any dependence of anticipatory postural adjustment (APA) on the difficulty of fine upper limb tasks and to document any effect of reticulospinal tract (RST) facilitation on APAs during such tasks.Methods:The study′s bivariate mixed design involved 4 different tasks and 3 different priming states. Thirteen healthy, male, right-handed subjects were recruited. They were asked to complete the 4 tasks of reaching, grasping a cup, pinching a card using the thumb or using the little finger, respectively for 10 times 1 in response to two different starting cues delivered through an earphone. Half of the trials with each task were initiated with 114dB white noise to startle and activate the reticulospinal tract (RST), while the others were activated with 80dB beeps as a control. Electromyographic signals were recorded from the bilateral sternocleidomastoid (SCM), lower trapezius (LT), latissimus dorsi (LD), lumbar erector spinae and right anterior deltoid muscles and also from the right flexor and extensor carpi radialis muscles (ECR/FCR). In the subsequent processing the electromyographic time domain and frequency domain indicators were converted into a pre-motor reaction time, a time to muscle peak contraction, an activation latency, and APA or compensatory postural adjustment (CPA) amplitude of the tested muscles. These were compared among the different tasks and stimuli. In addition, the 114dB test tasks were classified as two different priming status as SCM + and SCM - according to whether the sternocleidomastoid muscle (SCM) was activated in advance. Results:After RST activation the pre-motor reaction time and the time to peak contraction of all of the muscles were significantly shortened in all of the tasks. The deltoid muscle reaction times in the SCM + , SCM - and control states were (106.89±43.78)ms, (136.78±48.74)ms and (168.60±73.17)ms, respectively, and those differences are significant. The APA amplitudes of the contralateral LT and ipsilateral LD were significantly greater than normal, but the timing of muscle activation onset and the APA/CPA amplitudes of the ECR/FCR were not affected. The latency in the anticipatory muscle activation of the ECR in the little finger grip task was significantly shorter than that in reaching. Conclusions:The extensor carpi radialis show task-specific early activation in fine tasks of the upper limbs with different difficulties. RST activation can lead to early starting of expected actions, accelerate muscle contraction and increase APA amplitude of some trunk muscles, but it has no significant effect on APA/CPA amplitudes in the forearm muscles.

Objective To analyze the hepatitis B virus infection with extreme reduction of cholinesterase(CHE)not caused by liver synthesis dysfunction,and to explore its clinical significance.Methods The clinical data of 2 rare cases hospitalized in the 3rd people's hospital of Kunming in July 2021 and February 2022,including liver function,coagulation function,hepatitis B markers,hepatitis B virus volume,and whole exon sequencing,were collected and analyzed,and literature was reviewed.Results CHE was extremely reduced in 2 patients with HBV infection,liver synthesis function was good,and whole exon sequencing showed the presence of butyrylcholinesterase(BCHE)gene mutation.Conclusion The extremely low CHE in this case is not due to liver function disorder.Exon sequencing detected mutations in the BCHE gene in two patients.Screening for BCHE mutations may be necessary in patients with extremely low cholinesterase levels not due to liver dysfunction.

Objective:To evaluate the volume changes of cervical longus and cervical extensor after anterior cervical discectomy and fusion (ACDF), and the correlation with the clinical efficacy of patients.Methods:All of 57 patients with cervical spondylotic myelopathy who underwent single-segment ACDF surgery from January 2013 to December 2018 were analyzed. The follow-up time was 23.0±4.8 months (range 16-34 months). All included subjects underwent MR examination within 1 week before operation and 3rd, 12th months after operation and at the last follow-up. The axial section cross section area (AxCSA) of the cervical longus and the ratio of length to short diameter line (RLS) at the level of each disc of C 2-C 7 were measured on the axial T2WI. Calculate the volume of the cervical longus based on the layer thickness. At the same time, measure the cervical extensor cross-sectional area (CESA) of the same level including the multifidus, cervical semispinous muscle, semispinous head, splinter head, and cervical splinter muscles, and compare CESA with the corresponding vertebral cross-sectional area (VBA). The ratio is analyzed as the volume of the neck extensor muscle, namely CESA/VBA. At the 3rd and 12th months after operation and at the last follow-up, the axial pain was assessed by visual analogue scale (VAS) for assessing pain, and the modified Japanese Orthopedic Association score (mJOA) and the neck dysfunction index (NDI) were used to assess the functional status of the cervical spine. Analyze the morphological changes of thecervical longus and extensor cervical muscles before and after the operation and during the follow-up period, and analyze the correlation with VAS, mJOA, and NDI. Results:Compared with the preoperative period, the average AxCSA of the surgical segment decreased at the 3rd and 12th months after the operation and at the last follow-up. The difference was statistically significant ( F=24.113, P<0.05), which was changed from 140.84±19.51 mm 2 respectively reduce to 117.74±17.15 mm 2 ( t=6.714, P<0.05), 116.37±18.67 mm 2 ( t=6.841, P<0.05) and 116.27±18.65 mm 2 ( t=6.873, P<0.05). Compared with preoperatively, they were reduced by 16.40%, 17.37% and 17.45%, respectively, while the average RLS of surgical segments increased slightly, and the difference was statistically significant ( F=22.612, P<0.05), which increased from preoperative 1.97±0.67 to 2.73±0.60 (38.58% increased, t=6.380, P<0.05), 2.82±0.64 (43.15% increased, t=6.926, P<0.05) and 2.74±0.62 (39.09% increased, t=6.368, P<0.05). The volume of thecervical longus of the patients decreased after the operation, and the difference was statistically significant ( F=64.511, P<0.05), which decreased from 8853.48±458.65 mm 3 before the operation to 7834.53±461.59 mm 3 (11.51% decreased, t=11.822, P<0.05), 7926.42±456.24 mm 3 (10.47% decreased, t=10.819, P<0.05), 7892.38±450.78 mm 3 (10.86% decreased, t=11.283, P<0.05). There were no statistically significant differences in the non-surgical segment AxCSA, RLS and the volume of thecervical longus at the 3rd and 12th months after surgery and the last follow-up ( P>0.05). There was no statistically significant difference of CESA and CESA/VBA compared to preoperative in the surgical segment and non-surgical segment ( P>0.05). Pearson correlation analysis showed that the volume of cervical longus and VAS at the 3rd month ( r=-0.308, P<0.05), the 12th month ( r=-0.210, P<0.05) and the last follow-up ( r=-0.404, P<0.05) were negatively correlated; Among the volume of cervical longus and NDI in the 3rd month ( r=-0.511, P<0.05), 12th month ( r=-0.518, P<0.05) and the last follow-up ( r=-0.352, P<0.05), there was a negative correlation; However, there was no statistically significant correlation between the cervical longus muscle volume and mJOA at each follow-up time point ( P>0.05); There was no significant correlation between CESA/VBA and VAS, NDI, and mJOA at the 3rd, 12th and last follow-up ( P>0.05). Conclusion:The volume and morphology of cervical longus after ACDF was significantly reduced compared with that before the operation, but the volume and morphology of the cervical extensor muscle did not change significantly. ACDF surgery mainly affects the cervical longus corresponding to the surgical segment, and the volume is negatively correlated with the VAS and NDI during follow-up.

Exosomes are vesicles with a double globular membrane of lipids that can be secreted by a variety of cells, including stem cells. Exosomes have unique biological characteristics and irreplaceable powerful functions which play an important role in intercellular communication. The various cytokines, signal proteins, lipids and regulatory nucleic acids contained in stem cell exosomes can play a protective role against the injury of kidney, liver, heart, blood vessels and nerves. Stem cell exosomes delay the process of intervertebral disc degeneration by inhibiting the apoptosis of nucleus pulposus cells and increasing the synthesis of extracellular matrix, etc. The mechanism of its role is mainly through miRNA and related signaling pathways. Exosomes contain complex components. Although the mechanism of action of exosomes in intervertebral discs has been preliminarily explored, the components contained in exosomes are complex and the specific situation has not been fully understood, which still needs further study. In this review, the characteristics and functions of stem cell exosomes, extraction, identification and storage methods, the impacttovarious other tissues, as well as the effects on intervertebral discs and their mechanisms were elaborated in order to provide a basis for the study of intervertebral disc degenerative diseases.

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.

Objective To avoid the adverse consequences caused by human intervention in the process of blood transfusion and to promote the improvement of the quality index of blood transfusion specialist by the construction and application of closed loop management system for blood transfusion in mobile nursing information system. Methods In June 2014, the Nursing Department, the Information Department, the Blood Transfusion Department cooperated to analyzed the a variety of existing hidden dangers in blood transfusion process. After reengineering the related process of blood transfusion and setting up a certain of warning reminders, the closed loop management system for blood transfusion was finally constructed with the help of the research and development company using the mobile information system. A total of 2 202 cases from March to May 2014 before the application of the closed loop management system for blood transfusion in mobile nursing information system and 2 916 cases from January to March 2015 after the application of the system were investigated and analyzed, so as to compare the quality index and the incidence of adverse medical events. Results The implementation rate of blood transfusion in 4 hours, the abnormal cases in inspection per hour, the implementation rate of the inspection 15 min before transfusion, the cases of non-replacement of transfusion device in 4 hours all improved after the application of the closed loop management system for blood transfusion in mobile nursing information system, and the differences were statistically significant (P<0.01). In addition, there was no case of adverse medical event after the application of the closed loop management system for blood transfusion in mobile nursing information system. Conclusions Transforming the blood transfusion nursing process through information technology can realize the real-time monitoring of transfusion quality indicators and reduce the occurrence of adverse medical events, so as to ensure the transfusion safety.

Objective Studies and researches have indicated that the methylation level of PLAGL1 differentially methylated region (DMR) was associated with some development disorder syndromes.This project is purposed to prove whether methylation levels of PLAGL1 DMR is related to the fetal and early postnatal development.Methods We performed a meta-analysis of the published data on PLAGL1 DMR methylation levels in children with developmental disorders compared with that in normal children.Results PubMed,Medline,EMBASE,WanFang databases were systematically searched to identify relevant studies.We included 7 studies in this meta-analysis,with a total of 195 cases and 438 controls concerning 6 kinds of developmental disorder syndromes.The methylation level of PLAGL1 DMR was lower in children with abnormal growth (excess growth or retarded growth) than that in normal children,with a pooled percentage mean methylation difference (95％ confidence intervals) of-1.05 (-1.93,-0.17).On this basis,we analyzed the odds ratio (95％ confidence intervals) of hypomethylation of PLAGL1 DMR in abnormal growth children in comparison with normal children.The combined odds ratio (95％ confidence intervals) of hypomethylation in abnormal growth children is 2.18 (1.23,3.88) in comparison with normal children.Conclusion Hypomethylation of PLALG1 is actually a risk factor of suffering abnormal growth for children.