Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Objective To investigate whether miR-19a interacts with insulin-like growth factor 2 receptors(IGF-2R)in infantile hemangiomas(IHs)and affects the proliferation,migration,and adipogenesis of hemangioma stem cells(HemSCs).Methods HemSCs were isolated,screened and cultured from IH specimens.IGF-2R expression in HemSCs was identified using immunohistochemistry.HemSCs transfected with miR-19a mimics and inhibitors were subjected to CCK-8,wound healing,Transwell,qRT-PCR,and Western blot analyses.Results Compared with the control,the proliferation and migration rate of HemSCs treated with miR-19a inhibitors were significantly increased,and overexpression of miR-19a significantly inhibited IGF-2 induced cell migration and proliferation(P＜0.05).Conclusion MiR-19a may inhibit HemSCs proliferation,migration,and adipogenesis by targeting IGF-2R.

Objective Under the background of"breaking the Five-Only"and the evaluation reform of healthcare professionals'titles,it analyzed the willingness of healthcare professionals in public hospitals to disseminate health knowledge and its incentives and constraints.Furthermore,it explored potential pathways to improve the willingness of healthcare professionals to popular science and disseminate health knowledge.Methods From November to Decem-ber 2022,a self-designed online questionnaire was used to survey healthcare professionals in four tertiary hospitals in Shanghai.The questionnaire included basic information of healthcare professionals,analysis of the current situa-tion and demands of healthcare professionals in health knowledge dissemination,willingness of healthcare profes-sionals to disseminate health knowledge and influencing factors.Results A total of 762 healthcare professionals partici-pated in this survey,79.9%(608/762)expressed willingness to promote the dissemination of health knowledge.A multiple-factor logistic regression analysis revealed that intermediate professional title,achieving personal value and so-cial responsibility,increasing patient resources,professional title promotion,science promotion-related awards,being included in performance appraisals,and difficulty in capturing science promotion skills were the influential factors affecting the dissemination of health knowledge among healthcare professionals(P＜0.05).Conclusion The willing-ness of healthcare professionals to disseminate health knowledge was strong,and hospitals should motivate health-care professionals to disseminate health knowledge through building a long-term incentive mechanism,strengthening training in science popularization ability,and improving humanistic qualities.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

Objective To analyze the hotspots and developments in the field of language model-assisted artificial intelli-gence(Al)for antibody design and optimization in order to provide reference for research on development of antibodies.Methods By using CiteSpace software,hotspots of research were analyzed based on literature retrieved from the Web of Science,PubMed,and Scopus databases,focusing on three pivotal areas of research related to antibody design and optimization:the construction of pre-trained language models for antibodies,the generation of antibody sequences,and the prediction of three-dimensional structures of antibodies.In addition,this analysis reviewed the major advances in each of the specified research tasks,focusing on the delineation of similarities and differences across studies and dominating challenges in this field.Results From 2019(10 publications)to 2023(89 publications),the scale of and interest in this field kept increasing.Hotspots involved leveraging language models to assist the design or optimization of humanized,high-affinity,and highly specific antibodies.Within each research,methods were characterized by the diversity of model architectures,consistency of training data,and variations in training strategies.Challenges to the field included sparse antigen data,computational power limitations,and insufficient integration of wet and dry lab experiments.Conclusion Research in language model-assisted Al antibody design and optimization is gaining momentum and proves fruitful.However,researchers should be alert to the inadequate attention to antigen-antibody interactions and insufficient integration of experimental and computational validation,conduct more in-depth research and expand applications.

Objective:To investigate influences of curcumin on LPS-induced autophagy in corneal stromal cells by regulating phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(AKT)/mammalian target of rapamycin(mTOR)signaling pathway.Methods:Mouse corneal stromal cells were grouped into control group,LPS group(1 μg/μl LPS),L-Cur group(15 μmol/L curcumin),M-Cur group(30 μmol/L curcumin),H-Cur group(50 μmol/L curcumin),and H-Cur+740Y-P group(50 μmol/L curcumin+10 μmol/L PI3K activator 740Y-P).MTT was applied to detect effect of curcumin on corneal stromal cytotoxicity and cell viability;ELISA was applied to detect levels of inflammatory factors in corneal stromal cells;immunofluorescence staining was applied to detect levels of Beclin1 and LC3 in mouse corneal stromal cells;Western blot was applied to detect expressions of autophagy-related proteins and pathway-related proteins in corneal stromal cells.Results:0～90 μmol/L curcumin had no obvious toxicity to corneal stromal cells.Compared with control group,A570 nm,levels of Beclin1 and LC3Ⅱ/Ⅰ in LPS group were obviously decreased(P<0.05),levels of IL-6,IL-8,p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR were obviously increased(P<0.05);compared with LPS group,A570 nm,levels of Beclin1 and LC3Ⅱ/Ⅰ in L-Cur group,M-Cur group,H-Cur group were obviously increased in turn(P<0.05),levels of IL-6,IL-8,p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR were obviously decreased in turn(P<0.05);H-Cur+740Y-P eliminated beneficial effect of curcumin on corneal stromal cells.Conclusion:Curcumin may promote LPS-induced autophagy in corneal stromal cells by down-regulating PI3K/AKT/mTOR signaling pathway.

ObjectiveTo investigate the effect of hyperbaric oxygen combined with dynamic scalp acupuncture on motor function for stroke patients with hemiplegia, and compare the effect of dynamic scalp acupuncture inside or outside hyperbaric oxygen chamber. MethodsFrom January, 2021 to June, 2022, 72 stroke inpatients with hemiplegia in Fuyang People's Hospital were randomly divided into control group (n = 24), combination group 1 (n = 24) and combination group 2 (n = 24). All the patients received routine treatment, while the control group received dynamic scalp acupuncture, the combination group 1 received hyperbaric oxygen and dynamic scalp acupuncture outside the hyperbaric oxygen chamber, and the combination group 2 received hyperbaric oxygen and dynamic scalp acupuncture inside the hyperbaric oxygen chamber, for four weeks. They were assessed with National Institutes of Health Stroke Scale (NIHSS), modified Barthel Index (MBI), Berg Balance Scale (BBS), and Fugl-Meyer Assessment (FMA) before and after treatment. The rest pulse oximetry saturation (SpO₂)，the lowest SpO₂ (SpO_2L) and the variation of SpO₂ (ΔSpO₂) were measured in the first and last treatment. ResultsThe scores of NHISS, MBI, BBS and FMA increased in all the groups after treatment (|t| > 7.681, P < 0.001), and they were more in both the combination group 1 and the combination group 2 than in the control group (P < 0.05). During the first and last treatment, the rest SpO₂ and SpO_2L increased in the combination group 2 compared with the control group and the combination group 1 (P < 0.05), while ΔSpO₂ decreased (P < 0.05); and SpO_2L increased in the combination group 1 compared with the control group during the last treatment. ConclusionThe combination of hyperbaric oxygen and dynamic scalp acupuncture can significantly improve motor function and oxygen-carrying capacity in stroke patients with hemiplegia.

Diabetes peripheral neuropathy (DPN) is one of the most common complications of diabetes. It not only causes physical disability and unbearable pain, but also may lead to emotional and psychological problems, reduce the quality of life of patients, and increase mortality. Although early diagnosis of diabetes may improve the clinical prognosis, the occurrence of DPN is sometimes unavoidable and the treatment is limited. This article summarizes the clinical features, diagnosis, investigations and treatment of DPN by reviewing the latest literature.

Electromyography and neurophysiological examination are not only a clinical examination technique, but also play a more and more important role in the interpretation and solution of clinical problems of neuromuscular diseases by emphasizing the correlation between clinical and neurophysiology. In order to accurately locate the lesion site, further provide pathophysiological information, and assess the severity and course of the disease, it is necessary to develop a personalized examination program according to the symptoms and signs of patients, and it is also necessary to conduct systematic standardized training for clinicians and electrophysiological practitioners.

Objective:To study the neurophysiological features of Kennedy disease (KD) and to figure out the function of the nervous system.Methods:Subjects were recruited from the outpatient and the ward of Peking University Third Hospital from November 2010 to November 2022. Sixty patients with KD (29 patients with KD alone, 31 KD cases with the complication of diabetes mellitus) and 60 patients with diabetic polyneuropathy (DPN) were included in this study. Electrophysiological tests were performed in all subjects, including electromyogram, nerve conduction study, somaosensory evoked potential (SEP), contact heat evoked potential (CHEP) and triple stimulation technique (TST). Student′s t-tests were conducted to compare differences intra or inter groups of nerve conduction velocity and action potential of nerve conduction study, latency and interphase of SEP, initial peak latency of CHEP and other parameters. Results:Compared with the normative value, the amplitude of the sensory nerve action potential (SNAP) declined by 30%-80% in KD patients [median nerve (0.7±0.4) μV, ulnar nerve (0.8±0.3) μV, sural nerve (1.8±0.1) μV], the amplitude of the median and ulnar nerves was lower than the sural nerves ( t=2.43, P=0.010; t=2.40, P=0.010). The conduction time of peripheral segments of SEP and CHEP was prolonged by 115%-130%, while that of the central segments was prolonged by 104%-115% in SEP. TST test/TST control declined by 40%-60% in 17 patients with KD. The amplitude of SNAP declined by 30%-50% in patients with DPN [median nerve (2.9±0.5) μV, ulnar nerve (2.6±0.6) μV, sural nerve (1.6±0.2) μV], the amplitude of the sural nerves was lower than the median and ulnar nerves ( t=2.52, P=0.006; t=2.47, P=0.007). The conduction time of peripheral segments of SEP and CHEP was prolonged by 75%-112%, while that of the central segments was normal in both SEP and CHEP in DPN patients. Compared with DPN patients, the upper limb SNAP amplitude was lower in KD patients with the complication of diabetes mellitus [median nerve (0.7±0.3) μV, t=3.18, P=0.001; ulnar nerve (0.8±0.4) μV, t=3.20, P=0.001]. Conclusions:Sensory nerve is involved in patients with KD, including the large fiber and the small one. The central segments was abnormal in the deep sensory pathway, and the pyramid tract may be involved besides the anterior horn cell.