AIM: To investigate and analyze serum nitric oxide synthase 4(NOX4)and matrix metalloproteinase(MMP)-2 expressions in patients with diabetes mellitus(DM)complicated with neovascular glaucoma(NVG)and their clinical significance.METHODS: A prospective study was conducted on 161 patients with DM complicated with NVG admitted to Handan City Eye Hospital(The Third Hospital of Handan)from June 2020 to June 2023. Based on whether complications occurred 1 a after trabeculectomy in the study group patients, they were divided into a group with good prognosis(n=90)and a group with poor prognosis(n=71). During the same period, 161 patients with chronic angle-closure glaucoma without iris neovascularization were selected as the control group. ELISA method was applied to detect the expression levels of serum NOX4 and MMP-2. ROC curve was plotted to evaluate the diagnostic value and postoperative complication prediction value of NOX4 and MMP-2 in patients with DM complicated with NVG. Pearson method was applied to analyze the correlation of NOX4 and MMP-2 with vascular endothelial growth factor(VEGF)and interleukin-6(IL-6). Multivariate Logistic regression was applied to analyze the influencing factors of postoperative complications in the study group.RESULTS:The general information of the study group and control group of patients is comparable. Compared with the control group, the expression levels of serum NOX4, MMP-2, VEGF, and IL-6 in the study group were significantly increased(P<0.001). According to Pearson analysis, serum NOX4 and MMP-2 levels significantly positively correlated with VEGF and IL-6 levels, respectively(P<0.001). According to ROC curve, the AUC of NOX4 combined with MMP-2 in the diagnosis of DM complicated with NVG was better than that of individual diagnosis of NOX4(Z=3.341, P<0.05)and MMP-2(Z=2.788, P<0.05). The duration of DM, the proportion of people with intraocular pressure >21 mmHg, and the expression levels of NOX4, MMP-2, VEGF, and IL-6 in the poor prognosis group were all higher than those in the good prognosis group(P<0.001). The duration of DM, intraocular pressure >21 mmHg, the levels of NOX4, MMP-2, VEGF, and IL-6 were all risk factors for poor prognosis in DM patients with NVG(P<0.001). According to ROC curve, the combined prediction of NOX4 and MMP-2 for postoperative complications in patients with DM complicated by NVG was superior to the AUC predicted by NOX4(Z=3.727, P<0.05)and MMP-2(Z=2.219, P<0.05), respectively.CONCLUSION:NOX4 and MMP-2 are upregulated in the serum of patients with DM complicated by NVG. Combined detection of these two markers holds significant clinical value for the early diagnosis and prognosis of patients with DM complicated by NVG.

OBJECTIVE: To analyze the time characteristics of the Ethos online adaptive radiotherapy (OART) process in clinical practice and provide guidance for the comprehensive optimization of each stage of adaptive radiotherapy. METHODS: The study involved 61 patients with cervical, rectal, gastric, lung, esophageal, and breast cancers who underwent Ethos OART. The mean ± standard deviation of segmental time, total time, and target volume for these patients were tracked. The time characteristics for different cancer types were evaluated, and the average time for target and organ at risk (OAR) modifications was compared with the average target volume for each cancer type. RESULTS: Cervical cancer born the longest total treatment time, while breast cancer had the shortest. For all cancer types except breast cancer, the modification time for target and OAR was the most time-consuming segment. The average time for target and OAR modifications aligned with the trend of the average target volume. CONCLUSION The total treatment time for various cancers ranges from 15 to 35 minutes, indicating room for improvement.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Neoplasms/radiotherapy* ; Female

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To observe the clinical efficacy of withdrawal therapy based on regulating nutritive qi and defensive qi(shortened to Tiaohe Yingwei method)in treating sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.Methods Ninety patients with sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type were randomly divided into the treatment group and the control group,with 45 patients in each group.The control group was given oral use of Estazolam by 25%of weekly dose-reduction,while the treatment group was treated with Chinese medicinal decoction of Tiaohe Yingwei Zhumian Prescription based on Tiaohe Yingwei method together with Estazolam.The treatment course for the two groups lasted for 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)scores,total TCM syndrome scores,and Drug-withdrawal Syndrome Scale(DWSS)scores in the two groups were observed before and after treatment.After treatment,the efficacy for improving sleep efficiency value(IUSEV)and clinical safety in the two groups were evaluated.Results(1)During the trial,2 cases fell off in the treatment group,and 43 cases included in the statistics;3 cases fell off in the control group,and 42 cases included in the statistics.(2)After 4 weeks of treatment,the total effective rate for improving IUSEV of the treatment group was 88.37%(38/43),and that of the control group was 61.90%(26/42).The intergroup comparison by non-parametric rank-sum test showed that the efficacy for improving IUSEV in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,obvious reduction was shown in the overall PSQI scores and the scores of the items of sleep quality,time for falling asleep,sleep time,sleep efficiency,sleep disorder and daytime dysfunction in the two groups when compared with those before treatment(P＜0.05).The intergroup comparison showed that except for the items of sleep disorder and daytime dysfunction,the treatment group had stronger effect on decreasing the scores of the remaining items and the overall PSQI scores than the control group(P＜0.05).(4)After treatment,the total scores of TCM syndromes of both groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the total scores of TCM syndrome in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the total DWSS scores of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(6)During the course of treatment,no significant adverse reactions occurred in the two groups,or no abnormal changes were found in the safety indexes such as routine test of blood,urine and stool,liver and kidney function,and electrocardiogram of the patients.Conclusion Withdrawal therapy based on Tiaohe Yingwei method exerts certain effect for the treatment of sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.The therapy is effective on improving the quality of sleep and reducing the incidence of drug-withdrawal syndrome,and has a high safety.

Objective:To explore the caregiving feelings and needs of caregivers of children with β-thalassemia major.Methods:A semi-structured interview was conducted with 14 caregivers of children with β-thalassemia major who were treated at the Affiliated Hospital of Youjiang Medical University for Nationalities from December 2022 to March 2023, and the data were analyzed using the Colaizzi 7-step analysis method.Results:Caregivers of children with β-thalassemia major felt a greater burden of care, including declining physical and mental health, disruption of daily life rhythms and heavy financial burden. And their caregiving needs included psychological and emotional support, guidance on the physical and mental health of children, assurance of a stable blood supply and medical and social support.Conclusions:Caregivers of children with β-thalassemia major have a heavy burden of care and face various nursing difficulties in the daily care of children. Medical staff should actively take measures to meet their care needs and improve their care quality and quality of life.

Aim To explore the therapeutic effect of Qingjie Huagong decoction in regulating RIPK1/RIPK3/MLKL signaling pathway on pancreatic necrotic apoptosis in rats with severe acute pancreatitis(SAP)and the underlying mechanism.Methods The SAP rat model was established by retrograde pancreaticobili-ary injection of sodium taurocholate,and the sham-op-eration group,the model group,the group with differ-ent dosages of Qingjie Huagong decoction and the posi-tive control group were set up respectively.The group with different dosages of Qingjie Huagong decoction was given low,medium and high dosages of traditional Chinese medicine in the gastric gavage,the positive control group was given ulinastatin drug intervention,and the sham-operation and the model group were giv-en physiological saline in the gastric gavage;HE stai-ning was applied to observe pancreatic pathology;ELISA was used to measure the serum levels of α-am-ylase,IL-1β,IL-6,and TNF-α;immunohistochemis-try and Western blot were employed to determine the RIPK1,RIPK3,MLKL protein expression in rat pan-creatic tissue;and qRT-PCR was utilized to detect the transcription levels of R1PK1,RIPK3 and MLKL mR-NA in rat pancreatic tissue.Results Compared with the sham-operated group,the model group showed dif-fuse necrosis of pancreatic acinar cells,obvious inter-lobular septal edema,inflammatory cell infiltration,significantly higher levels of α-amylase,IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher ex-pression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P＜0.01)in the model group;com-pared with the model group,the Qingjie Huagong de-coction dose groups and positive control group signifi-cantly improved pancreatic histopathology,reduced pancreatic tissue necrosis and apoptosis,lowered the expression levels of α-amylase,IL-1 β,IL-6 and TNF-α(P＜0.01),and reduced the expression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P＜0.01).Conclusions Qingjie Huagong decoction may improve the necrotic apoptosis of pancreatic tissue by regulating the RIPK1/RIPK3/MLKL signaling path-way,thus playing a role in protecting pancreatic tissue and slowing down the progression of the disease.

Objective:To compare and study the improvement of different iterative reconstruction(IR)algorithms of the tomotherapy(TOMO)Radixact system on the image quality of megavoltage computed tomography(MVCT)imaging system,and the influence of that on the precision of automatic registration,and to explore the reconstruction algorithm that is suitable for clinical application.Methods:Using the MVCT imaging system to respectively scan the Tomo-Phantom HE phantom and the Catphan 604 phantom,and to analyze three groups of images were generated by three kinds of reconstruction algorithms,which included the Standard(STD)algorithm,IR General(IR-G)algorithm and IR Soft Tissue(IR-ST)algorithm,in MVCT image.The noise index(NI),uniformity index(UI)of image,modulation transfer function(MTF),low contrast visibility(LCV)index and contrast-to-noise ratio(CNR)of three groups of images were calculated respectively.The Lucy phantom was used to test the accuracy of automatic registration algorithm.The registration data of four dimensions,included left-right(X-axis),head-foot(Y-axis),vertical(Z-axis)and free rotation(Roll)around the Y-axis,were used to conduct verification analysis for the influences of them on the precision of automatic registration.Results:The NI values of IR-G and IR-ST reconstruction algorithms were respectively 39.58±0.10 and 14.62±0.26,which were better than 39.58±0.10 of STD algorithm,and the UI values of them were respectively 19.87±0.83 and 15.84±2.51,which were better than 24.51±1.81 of STD algorithm,and LCV values of them were respectively 2.50±0.03 and 1.74±0.11,which were better than 3.67±0.04 of STD algorithm.All of them appeared significant increase,but the resolution with high contrast of MTF were respectively 0.23 and 0.21,which were lower than 0.32 of STD.The overall image quality of the IR algorithms was superior to that of the STD algorithm.In the accuracy test of the automatic registration algorithm,the registration precisions of IR-G and IR-ST algorithms on Y-axis were respectively(0.360±0.142)mm and(0.245±0.050)mm,which were significantly higher than 0.145±0.136 of STD algorithm,and the differences of them were significant(Z=6.0,15.0,P<0.05).The differences of registration precisions of other directions were not significant(P>0.05).Conclusion:The IR algorithm has advantages in terms of noise,uniformity and resolution with low-contrast,however,it shows reduction on resolution with high-contrast.This reduction of resolution with high-contrast do not lead to the decrease of the precision of automatic registration.

Objective:To quantitatively analyze the differences in image quality and generated synthetic-computed tomography(sCT)between cone beam CT(CBCT)and iteration CBCT(iCBCT),which based on filtered back projection(FBP)and iterative reconstruction(IR)techniques of Varian Ethos adaption system.Methods:Using the special Catphan604 phantom of the test of CT image quality,five times of scanning series of CBCT and iCBCT were respectively performed based on thoracic and abdominal scanning protocols,so as to obtain four sets of images,and each set of image included the CBCT image,the composited sCT and iCBCT images based on CBCT,the composited sCT bases on iCBCT.The noise power spectrum(NPS),image uniformity(UI),modulation transfer function(MTF),low-contrast visibility(LCV)and contrast-to-noise ratio(CNR)of them were analyzed.Additionally,a retrospective analysis was conducted on images of six patients who underwent clinical radiotherapy,and the images of them were obtained by using thoracic and abdominal scanning protocols.The sCT images,which were generated by deformable registrations on the basis of CBCT and iCBCT,were analyzed,and they were compared with located CT images,and their mean absolute error(MAE)and root mean square error(RMSE)were further quantitatively analyzed.Results:Compared to CBCT,iCBCT significantly reduced NPS(thoracic images reduced by 0.08,abdominal images reduced by 0.06).The UI values of thoracic images and abdominal images of iCBCT were respectively 0.37 and 0.28,and those of CBCT were respectively 0.65 and 0.39.The LCV values of thoracic images and abdominal images of iCBCT were respectively 0.67 and 0.56,and those of CBCT were respectively 0.93 and 0.90.The MTF50％were 0.28 lp/mm except abdominal image of iCBCT was 0.29 lp/mm.The resolution rate of high contrast between iCBCT and CBCT was basic consistency.The differences of similarity analysis of the generated sCT and located CT bases on CBCT and iCBCT was no significant(P＞0.05).Conclusion:The image quality of iCBCT is superior to conventional CBCT.The accuracy of CT value of generated sCT bases on CBCT and iCBCT can meet requirement,and both of them can be used in the dose calculation of adaptive radiotherapy.

Objective To systematically evaluate the effect of exercise therapy on body structure,function,and activity and partici-pation in patients with chronic nonspecific neck pain(CNSNP)based on the International Classification of Func-tioning,Disability and Health(ICF)framework. Methods A PICO framework was constructed,and randomized controlled trials(RCTs)on the intervention of different types of exercise therapy for patients with CNSNP were retrieved from databases of CBM,Wanfang data,VIP,CNKI,Cochrane Library,Embase,PubMed and Web of Science,from the establishment to March,2024.The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database(PEDro)scale,and the evidence quality of the outcome indicators was evaluated using GRADE.Data were syn-thesized and analyzed using RevMan 5.3,and the risk of bias was evaluated using Stata 18.0. Results A total of eleven RCTs involving 668 subjects were included.The scores of PEDro scale were five to eight.The types of interventions included muscle strength training,stability training,proprioception training,Yoga and Pi-lates.The control groups received placebo,physical factor therapy and health education.Exercise therapy could increase the craniovertebral angle(SMD=0.84,95%CI 0.42 to 1.26,P<0.001),reduce the Visual Analogue Scale score(SMD=-2.05,95%CI-2.58 to-1.52,P<0.001),increase the pressure pain threshold(MD=112.27,95%CI 75.03 to 149.50,P<0.001),increase the range of motion of cervical forward(SMD=1.24,95%CI 0.34 to 2.15,P=0.007)and lateral(SMD=1.52,95%CI 0.40 to 2.65,P=0.008)flexion,and improve the endurance of the deep cervical flexors(SMD=1.02,95%CI 0.10 to 1.94,P=0.03)and position sense of the cervical spine(SMD=-1.00,95%CI-1.47 to-0.53,P<0.001);however,it was not significant in improving the range of motion of backward flexion(SMD=0.85,95%CI-1.04 to 2.75,P=0.38)and rotation(SMD=1.65,95%CI-0.35 to 3.65,P=0.11).Exercise therapy could also reduce the Neck Disability Index score(MD=-11.88,95%CI-16.09 to-7.68,P<0.001),and it was no significant in the Short-Form-36 score(MD=19.04,95%CI-3.00 to 41.08,P=0.09). Conclusion Exercise therapy can improve head posture,pain,motion of forward flexion and lateral flexion,endurance of the cervical flexors and joint position sense,and the overall function in patients with CNSNP.However,fur-ther researches are needed to verify the effects on cervical backward flexion and rotation,and quality of life.

The 68 Center for Drug Evaluation recommend approved innovative drugs between 2019 and 2021 evaluation situation was summarized in this article,to analyzes the innovative drugs research and development trend and the influence of the drug evaluation and approval system reform.Meanwhile,after sorting out the clinical trials inspection report,to analyze the clinical trials on-site inspection of innovative drugs,and summarized the common defects,hope to provide reference and suggestions for subsequent innovative drug application and high-quality drug clinical trials.